ఎంజ్య్మే కినేతిచ్స్ అండ్ డయాగ్నోసిస్

1. Introduction to Enzymes
2. Enzyme Classifications
3. Role of Coenzymes
4. Enzyme Activity Relative to Substrate Type
5. Enzyme-Substrate Interactions
6. Chemical Reactions and Rates
7. Chemical Reaction Order
8. Enzymes as Biological Catalysts
9. Michaelis-Menton Kinetics
10.Inhibition of Enzyme Catalyzed Reactions
11.Regulation of Enzyme Activity
12. Allosteric Enzymes
13.Enzymes in the Diagnosis of Pathology

Introduction to Enzymes

Enzymes are biological catalysts responsible for supporting almost all of the chemical reactions that maintain animal homeostasis. Because of their role in maintaining life processes, the assay and pharmacological regulation of enzymes have become key elements in clinical diagnosis and therapeutics. The macromolecular components of almost all enzymes are composed of protein, except for a class of RNA modifying catalysts known as ribozymes. Ribozymes are molecules of ribonucleic acid that catalyze reactions on the phosphodiester bond of other RNAs.

Enzymes are found in all tissues and fluids of the body. Intracellular enzymes catalyze the reactions of metabolic pathways. Plasma membrane enzymes regulate catalysis within cells in response to extracellular signals, and enzymes of the circulatory system are responsible for regulating the clotting of blood. Almost every significant life process is dependent on enzyme activity.
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Enzyme Classifications

Traditionally, enzymes were simply assigned names by the investigator who discovered the enzyme. As knowledge expanded, systems of enzyme classification became more comprehensive and complex. Currently enzymes are grouped into six functional classes by the International Union of Biochemists (I.U.B.).



Number
Classification
Biochemical Properties

1.
Oxidoreductases
Act on many chemical groupings to add or remove hydrogen atoms.

2.
Transferases
Transfer functional groups between donor and acceptor molecules. Kinases are specialized transferases that regulate metabolism by transferring phosphate from ATP to other molecules.

3.
Hydrolases
Add water across a bond, hydrolyzing it.

4.
Lyases
Add water, ammonia or carbon dioxide across double bonds, or remove these elements to produce double bonds.

5.
Isomerases
Carry out many kinds of isomerization: L to D isomerizations, mutase reactions (shifts of chemical groups) and others.

6.
Ligases
Catalyze reactions in which two chemical groups are joined (or ligated) with the use of energy from ATP.



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These rules give each enzyme a unique number. The I.U.B. system also specifies a textual name for each enzyme. The enzyme's name is comprised of the names of the substrate(s), the product(s) and the enzyme's functional class. Because many enzymes, such as alcohol dehydrogenase, are widely known in the scientific community by their common names, the change to I.U.B.-approved nomenclature has been slow. In everyday usage, most enzymes are still called by their common name.

Enzymes are also classified on the basis of their composition. Enzymes composed wholly of protein are known as simple enzymes in contrast to complex enzymes, which are composed of protein plus a relatively small organic molecule. Complex enzymes are also known as holoenzymes. In this terminology the protein component is known as the apoenzyme, while the non-protein component is known as the coenzyme or prosthetic group where prosthetic group describes a complex in which the small organic molecule is bound to the apoenzyme by covalent bonds; when the binding between the apoenzyme and non-protein components is non-covalent, the small organic molecule is called a coenzyme. Many prosthetic groups and coenzymes are water-soluble derivatives of vitamins. It should be noted that the main clinical symptoms of dietary vitamin insufficiency generally arise from the malfunction of enzymes, which lack sufficient cofactors derived from vitamins to maintain homeostasis.

The non-protein component of an enzyme may be as simple as a metal ion or as complex as a small non-protein organic molecule. Enzymes that require a metal in their composition are known as metalloenzymes if they bind and retain their metal atom(s) under all conditions with very high affinity. Those which have a lower affinity for metal ion, but still require the metal ion for activity, are known as metal-activated enzymes.

Role of Coenzymes

The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another. The chemical groups carried can be as simple as the hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD; or they can be even more complex than the amine (-NH2) carried by pyridoxal phosphate.

Since coenzymes are chemically changed as a consequence of enzyme action, it is often useful to consider coenzymes to be a special class of substrates, or second substrates, which are common to many different holoenzymes. In all cases, the coenzymes donate the carried chemical grouping to an acceptor molecule and are thus regenerated to their original form. This regeneration of coenzyme and holoenzyme fulfills the definition of an enzyme as a chemical catalyst, since (unlike the usual substrates, which are used up during the course of a reaction) coenzymes are generally regenerated.
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Enzyme Relative to Substrate Type

Although enzymes are highly specific for the kind of reaction they catalyze, the same is not always true of substrates they attack. For example, while succinic dehydrogenase (SDH) always catalyzes an oxidation-reduction reaction and its substrate is invariably succinic acid, alcohol dehydrogenase (ADH) always catalyzes oxidation-reduction reactions but attacks a number of different alcohols, ranging from methanol to butanol. Generally, enzymes having broad substrate specificity are most active against one particular substrate. In the case of ADH, ethanol is the preferred substrate.

Enzymes also are generally specific for a particular steric configuration (optical isomer) of a substrate. Enzymes that attack D sugars will not attack the corresponding L isomer. Enzymes that act on L amino acids will not employ the corresponding D optical isomer as a substrate. The enzymes known as racemases provide a striking exception to these generalities; in fact, the role of racemases is to convert D isomers to L isomers and vice versa. Thus racemases attack both D and L forms of their substrate.

As enzymes have a more or less broad range of substrate specificity, it follows that a given substrate may be acted on by a number of different enzymes, each of which uses the same substrate(s) and produces the same product(s). The individual members of a set of enzymes sharing such characteristics are known as isozymes. These are the products of genes that vary only slightly; often, various isozymes of a group are expressed in different tissues of the body. The best studied set of isozymes is the lactate dehydrogenase (LDH) system. LDH is a tetrameric enzyme composed of all possible arrangements of two different protein subunits; the subunits are known as H (for heart) and M (for skeletal muscle). These subunits combine in various combinations leading to 5 distinct isozymes. The all H isozyme is characteristic of that from heart tissue, and the all M isozyme is typically found in skeletal muscle and liver. These isozymes all catalyze the same chemical reaction, but they exhibit differing degrees of efficiency. The detection of specific LDH isozymes in the blood is highly diagnostic of tissue damage such as occurs during cardiac infarct.
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Enzyme-Substrate Interactions

The favored model of enzyme substrate interaction is known as the induced fit model. This model proposes that the initial interaction between enzyme and substrate is relatively weak, but that these weak interactions rapidly induce conformational changes in the enzyme that strengthen binding and bring catalytic sites close to substrate bonds to be altered. After binding takes place, one or more mechanisms of catalysis generates transition- state complexes and reaction products. The possible mechanisms of catalysis are four in number:



1. Catalysis by Bond Strain: In this form of catalysis, the induced structural rearrangements that take place with the binding of substrate and enzyme ultimately produce strained substrate bonds, which more easily attain the transition state. The new conformation often forces substrate atoms and bulky catalytic groups, such as aspartate and glutamate, into conformations that strain existing substrate bonds.



2. Catalysis by Proximity and Orientation: Enzyme-substrate interactions orient reactive groups and bring them into proximity with one another. In addition to inducing strain, groups such as aspartate are frequently chemically reactive as well, and their proximity and orientation toward the substrate thus favors their participation in catalysis.



3. Catalysis Involving Proton Donors (Acids) and Acceptors (Bases): Other mechanisms also contribute significantly to the completion of catalytic events initiated by a strain mechanism, for example, the use of glutamate as a general acid catalyst (proton donor).



4. Covalent Catalysis: In catalysis that takes place by covalent mechanisms, the substrate is oriented to active sites on the enzymes in such a way that a covalent intermediate forms between the enzyme or coenzyme and the substrate. One of the best-known examples of this mechanism is that involving proteolysis by serine proteases, which include both digestive enzymes (trypsin, chymotrypsin, and elastase) and several enzymes of the blood clotting cascade. These proteases contain an active site serine whose R group hydroxyl forms a covalent bond with a carbonyl carbon of a peptide bond, thereby causing hydrolysis of the peptide bond.
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Chemical Reactions and Rates

According to the conventions of biochemistry, the rate of a chemical reaction is described by the number of molecules of reactant(s) that are converted into product(s) in a specified time period. Reaction rate is always dependent on the concentration of the chemicals involved in the process and on rate constants that are characteristic of the reaction. For example, the reaction in which A is converted to B is written as follows:

A ------> B

The rate of this reaction is expressed algebraically as either a decrease in the concentration of reactant A:



-[A] = k[B]

or an increase in the concentration of product B:

[B] = k[A]



In the second equation (of the 3 above) the negative sign signifies a decrease in concentration of A as the reaction progresses, brackets define concentration in molarity and the k is known as a rate constant. Rate constants are simply proportionality constants that provide a quantitative connection between chemical concentrations and reaction rates. Each chemical reaction has characteristic values for its rate constants; these in turn directly relate to the equilibrium constant for that reaction. Thus, reaction can be rewritten as an equilibrium expression in order to show the relationship between reaction rates, rate constants and the equilibrium constant for this simple case. The rate constant for the forward reaction is defined as k+1 and the reverse as k-1.

At equilibrium the rate (v) of the forward reaction (A -----> B) is--- by definition--- equal to that of the reverse or back reaction (B -----> A), a relationship which is algebraically symbolized as:

vforward = vreverse

where, for the forward reaction:

vforward = k+1[A]

and for the reverse reaction:

vreverse = k-1[B]



In the above equations, k+1 and k-1 represent rate constants for the forward and reverse reactions, respectively. The negative subscript refers only to a reverse reaction, not to an actual negative value for the constant. To put the relationships of the two equations into words, we state that the rate of the forward reaction [vforward] is equal to the product of the forward rate constant k+1 and the molar concentration of A. The rate of the reverse reaction is equal to the product of the reverse rate constant k-1 and the molar concentration of B.

At equilibrium, the rate of the forward reaction is equal to the rate of the reverse reaction leading to the equilibrium constant of the reaction and is expressed by:



[B]/[A] = k+1/k-1 = Keq

This equation demonstrates that the equilibrium constant for a chemical reaction is not only equal to the equilibrium ratio of product and reactant concentrations, but is also equal to the ratio of the characteristic rate constants of the reaction.
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Chemical Reaction Order

Reaction order refers to the number of molecules involved in forming a reaction complex that is competent to proceed to product(s). Empirically, order is easily determined by summing the exponents of each concentration term in the rate equation for a reaction. A reaction characterized by the conversion of one molecule of A to one molecule of B with no influence from any other reactant or solvent is a first-order reaction. The exponent on the substrate concentration in the rate equation for this type of reaction is 1. A reaction with two substrates forming two products would a second-order reaction. However, the reactants in second- and higher- order reactions need not be different chemical species. An example of a second order reaction is the formation of ATP through the condensation of ADP with orthophosphate:



ADP + H2PO4 <----> ATP + H2O

For this reaction the forward reaction rate would be written as:

vforward = k1[ADP][H2PO4]

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Enzymes as Biological Catalysts

In cells and organisms most reactions are catalyzed by enzymes, which are regenerated during the course of a reaction. These biological catalysts are physiologically important because they speed up the rates of reactions that would otherwise be too slow to support life. Enzymes increase reaction rates--- sometimes by as much as one millionfold, but more typically by about one thousand fold. Catalysts speed up the forward and reverse reactions proportionately so that, although the magnitude of the rate constants of the forward and reverse reactions is are increased, the ratio of the rate constants remains the same in the presence or absence of enzyme. Since the equilibrium constant is equal to a ratio of rate constants, it is apparent that enzymes and other catalysts have no effect on the equilibrium constant of the reactions they catalyze.

Enzymes increase reaction rates by decreasing the amount of energy required to form a complex of reactants that is competent to produce reaction products. This complex is known as the activated state or transition state complex for the reaction. Enzymes and other catalysts accelerate reactions by lowering the energy of the transition state. The free energy required to form an activated complex is much lower in the catalyzed reaction. The amount of energy required to achieve the transition state is lowered; consequently, at any instant a greater proportion of the molecules in the population can achieve the transition state. The result is that the reaction rate is increased.
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Michaelis-Menton Kinetics

In typical enzyme-catalyzed reactions, reactant and product concentrations are usually hundreds or thousands of times greater than the enzyme concentration. Consequently, each enzyme molecule catalyzes the conversion to product of many reactant molecules. In biochemical reactions, reactants are commonly known as substrates. The catalytic event that converts substrate to product involves the formation of a transition state, and it occurs most easily at a specific binding site on the enzyme. This site, called the catalytic site of the enzyme, has been evolutionarily structured to provide specific, high-affinity binding of substrate(s) and to provide an environment that favors the catalytic events. The complex that forms, when substrate(s) and enzyme combine, is called the enzyme substrate (ES) complex. Reaction products arise when the ES complex breaks down releasing free enzyme.

Between the binding of substrate to enzyme, and the reappearance of free enzyme and product, a series of complex events must take place. At a minimum an ES complex must be formed; this complex must pass to the transition state (ES*); and the transition state complex must advance to an enzyme product complex (EP). The latter is finally competent to dissociate to product and free enzyme. The series of events can be shown thus:



E + S <---> ES <---> ES* <---> EP <---> E + P



The kinetics of simple reactions like that above were first characterized by biochemists Michaelis and Menten. The concepts underlying their analysis of enzyme kinetics continue to provide the cornerstone for understanding metabolism today, and for the development and clinical use of drugs aimed at selectively altering rate constants and interfering with the progress of disease states. The Michaelis-Menten equation is a quantitative description of the relationship among the rate of an enzyme- catalyzed reaction [v1], the concentration of substrate [S] and two constants, Vmax and Km (which are set by the particular equation). The symbols used in the Michaelis-Menton equation refer to the reaction rate [v1], maximum reaction rate (Vmax), substrate concentration [S] and the Michaelis-Menton constant (Km).

Thermodinemisc of Biochemistry

• Definition of Keq, Kw and pH
• Definition of pKa
• The Henderson-Hasselbalch Equation
• Definition of Buffering
• Significance of Blood Buffering
• Ampholyte, Polyampholyte, pI and Zwitterion
• Definition of Solvation and Hydration
• Kidneys and Acid-Base Balance
o Sodium Bicarbonate Reabsorption
o Excretion of Acid
o Ammonia Secretion
 Neurotoxicity of Ammonia
o Acidosis and Alkalosis

Ionic Equilibrium

Keq, Kw and pH
As H2O is the medium of biological systems one must consider the role of this molecule in the dissociation of ions from biological molecules. Water is essentially a neutral molecule but will ionize to a small degree. This can be described by a simple equilibrium equation:
H2O <-------> H+ + OH- Eqn. 1
This equilibrium can be calculated as for any reaction:
Keq = [H+][OH-]/[H2O] Eqn. 2
Since the concentration of H2O is very high (55.5M) relative to that of the [H+] and [OH-], consideration of it is generally removed from the equation by multiplying both sides by 55.5 yielding a new term, Kw:
Kw = [H+][OH-] Eqn. 3
This term is referred to as the ion product. In pure water, to which no acids or bases have been added:
Kw = 1 x 10-14 M2 Eqn. 4
As Kw is constant, if one considers the case of pure water to which no acids or bases have been added:
[H+] = [OH-] = 1 x 10-7 M Eqn. 5
This term can be reduced to reflect the hydrogen ion concentration of any solution. This is termed the pH, where:
pH = -log[H+] Eqn. 6
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pKa
Acids and bases can be classified as proton donors and proton acceptors, respectively. This means that the conjugate base of a given acid will carry a net charge that is more negative than the corresponding acid. In biologically relavent compounds various weak acids and bases are encountered, e.g. the acidic and basic amino acids, nucleotides, phospholipids etc.
Weak acids and bases in solution do not fully dissociate and, therefore, there is an equilibrium between the acid and its conjugate base. This equilibrium can be calculated and is termed the equilibrium constant = Ka. This is also sometimes referred to as the dissociation constant as it pertains to the dissociation of protons from acids and bases.
In the reaction of a weak acid:
HA <-----> A- + H+ Eqn. 7
the equlibrium constant can be calculated from the following equation:
Ka = [H+][A-]/[HA] Eqn. 8
As in the case of the ion product:
pKa = -logKa Eqn. 9
Therefore, in obtaining the -log of both sides of the equation describing the dissociation of a weak acid we arrive at the following equation:
-logKa = -log[H+][A-]/[HA] Eqn. 10
Since as indicated above -logKa = pKa and taking into account the laws of logrithms:
pKa = -log[H+] -log[A-]/[HA] Eqn. 11
pKa = pH -log[A-]/[HA] Eqn. 12
From this equation it can be seen that the smaller the pKa value the stronger is the acid. This is due to the fact that the stronger an acid the more readily it will give up H+ and, therefore, the value of [HA] in the above equation will be relatively small.
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Clinical Significance of Blood Buffering
The pH of blood is maintained in a narrow range around 7.4. Even relatively small changes in this value of blood pH can lead to severe metabolic consequences. Therefore, blood buffering is extremely important in order to maintain homeostasis. Although the blood contains numerous cations (e.g., Na+, K+, Ca2+ and Mg2+) and anions (e.g., Cl-, PO43- and SO42-) that can, as a whole, play a role in buffering, the primary buffers in blood are hemoglobin in erythrocytes and bicarbonate ion (HCO3-) in the plasma. Buffering by hemoglobin is accomplished by ionization of the imidazole ring of histidines in the protein.
The formation of bicarbonate ion in blood from CO2 and H2O allows the transfer of relatively insoluble CO2 from the tissues to the lungs, where it is expelled. The major source of CO2 in the tissues comes from the oxidation of ingested carbon compounds.
Carbonic acid is formed from the reaction of dissolved CO2 with H2O. The relationship between carbonic acid and bicarbonate ion formation is shown in equations 16 and 17.

CO2 + H2O <----> H2CO3 Eqn. 16
H2CO3 <----> H+ + HCO3- Eqn. 17
The reactions shown in equations 16 and 17 occur predominately in the erythrocytes, since nearly all of the CO2 leaving tissues via the capillary endothelium is taken up by these cells. This reaction is catalyzed by carbonic anhydrase. Ionization of carbonic acid then occurs spontaneously (as shown in equation 17), yielding bicarbonate ion.
Carbonic acid is a relatively strong acid with a pKa of 3.8. However, carbonic acid is in equilibrium with dissolved CO2. Therefore, the equilibrium equation for the sum of equations 16 and 17 requires a conversion factor, since CO2 is a dissolved gas. This factor has been shown to be approximately 0.03 times the partial pressure of CO2 (PCO2). When this is entered into the Henderson-Hasselbalch equation:

pH = 6.1 + log [HCO3-/(0.03)(PCO2)] Eqn. 18
where the apparent pKa for bicarbonate formation, 6.1, has been introduced into equation 18.
The PCO2 in the peripheral tissues is approximately 50mm Hg, whereas in the blood entering the peripheral tissues it is approximately 40mm Hg. This difference results in the diffusion of CO2 from the tissues into the blood in the capillaries of the periphery. When the CO2 is converted to H2CO3 within the erythrocytes and then ionizes, the hydrogen ions (H+) are buffered by hemoglobin. The production of H+ ions, within erythrocytes, and their subsequent buffering by hemoglobin results in a reduced affinity of hemoglobin for oxygen. This leads to a release of O2 to the peripheral tissues, a phenomenon is termed the Bohr effect.



Representation of the transport of CO2 from the tissues to the blood with delivery of O2 to the tissues. The opposite process occurs when O2 is taken up from the alveoli of the lungs and the CO2 is expelled. All of the processes of the transport of CO2 and O2 are not shown such as the formation and ionization of carbonic acid in the plasma. The latter is a major mechanism for the transport of CO2 to the lungs, i.e. in the plasma as HCO3-. The H+ produced in the plasma by the ionization of carbonic acid is buffered by phosphate (HPO42-) and by proteins. Additionally, some 15% of the CO2 is transported from the tissues to the lungs as hemoglobin carbamate as shown in Eqn. 19.

As CO2 passes from the tissues to the plasma a minor amount of carbonic acid takes form and ionizes. The H+ ions are then buffered predominantly by proteins and phosphate ions in the plasma. As the concentration of bicarbonate ions rises in erythrocytes, an osmotic imbalance occurs. The imbalance is relieved as bicarbonate ion leaves the erythrocytes in exchange for chloride ions from the plasma. This phenomenon is known as the chloride shift which is also shown in the diagram above. Therefore, the majority of the bicarbonate ion formed as CO2 leaves the peripheral tissues is transported by the plasma to the lungs.
Around 15% of CO2 transport from the tissues to the lungs occurs through a reversible combination with non-ionized amino groups (-NH2) of hemoglobin forming what is termed hemoglobin carbamate.
Hemoglobin-NH2 + CO2 <---> Hemoglobin-NH-COO- + H+ Eqn. 19
The formation of hemoglobin carbamate results in a reduced affinity of hemoglobin for O2 thus favoring dissociation of bound oxygen in the tissues where the concentration of CO2 is high. The process is reversed when the erythrocytes enter the lungs and the partial pressure of O2 is elevated.
The partial pressure of O2 (PO2) in the pulmonary alveoli is higher than the PO2 of the entering erythrocytes that contain predominantly deoxygenated hemoglobin. This increased PO2 leads to oxygenation of hemoglobin and release of H+ ions from the hemoglobin. The released H+ ions combine with the bicarbonate ions to form H2CO3. Cellular carbonic anhydrase then catalyzes the reverse of reaction 17, leading to release of CO2 from erythrocytes. Owing to the PCO2 gradient (described above), the CO2 diffuses from the blood to the alveoli where it is expelled.
The great utility of bicarbonate as a physiological buffer stems from the fact that if excess acid is added to the blood the concentration of bicarbonate ion declines and the level of CO2 increases. The CO2 then passes from capillaries in the pulmonary alveoli and is expelled. As a consequence, the H+ ion concentration drives reaction 17 to the left and bicarbonate ion acts as a buffer until all of the hydrogen ion is consumed. Conversely, when excess base is added to the blood, CO2 is consumed by carbonic acid and replaced by metabolic reactions within the body.
If blood is not adequately buffered, the result may be metabolic acidosis or metabolic alkalosis. These physiological states can be reached if a metabolic defect results in the inappropriate accumulation or loss of acidic or basic compounds. These compounds may be ingested, or they may accumulate as metabolic by-products such as acetoacetic acid and lactic acid. Both of these will ionize, thereby increasing the level of H+ ions that will in turn remove bicarbonate ions from the blood and alter blood pH. The predominant defect in acid or base elimination arises when the excretory system of the kidneys is impaired. Alternatively, if the lungs fail to expel accumulated CO2 adequately and CO2 accumulates in the body, the result will be respiratory acidosis. If a decrease in PCO2 within the lungs occurs, as during hyperventilation, the result will be respiratory alkalosis.


Ampholytes, Polyampholytes, pI and Zwitterion
Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.
For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the -COOH group and the pK for the -NH2 group:

pI = [pKa-(COOH) + pKa-(NH3+)]/2 Eqn. 20

For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.
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Solvation and Hydration shells
Depending on the pH of a solution, macromolecules such as proteins which contain many charged groups, will carry substantial net charge, either positive or negative. Cells of the body and blood contain many polyelectrolytes (molecules that contain multiple same charges, e.g. DNA and RNA) and polyampholytes that are in close proximity. The close association allows these molecules to interact through opposing charged groups. The presence, in cells and blood, of numerous small charged ions (e.g. Na+, Cl-, Mg2+, Mn2+, K+) leads to the interaction of many small ions with the larger macroions. This interaction can result in a shielding of the electrostatic charges of like-charged molecules. This electrostatic shielding allows macroions to become more closely associated than predicted based upon their expected charge repulsion from one another. The net effect of the presence of small ions is to maintain the solubility of macromolecules at pH ranges near their pI. This interaction between solute (e.g. proteins, DNA, RNA, etc.) and solvent (e.g. blood) is termed solvation or hydration. The opposite effect to solvation occurs when the salt (small ion) concentration increases to such a level as to interfere with the solvation of proteins by H2O. This results from the H2O forming hydration shells around the small ions.
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Role of the Kidneys in Acid-Base Balance
The kidneys function to filter the plasma that passes through the nephrons. Filtration of the plasmas occurs in the glomerular capillaries of the nephron. These capillaries allow the passage of water and low molecular weight solutes (less than 70 kDa) into the capsular space. The filtrate then passes through the proximal and distal convoluted tubules where reabsorption of water and many solutes takes place. In the course of glomerular filtration and tubule reabsorption the composition of the plasma changes generating the typical composition of urine. From a biochemical standpoint the kidneys serve important roles in the regulation of plasma acid-base balance and the elimination of nitrogenous wastes.

Sodium Bicarbonate Reabsorption
Regulation of plasma acid-base balance is primarily effected within the kidney through control over HCO3- reabsorption and secretion of H+. Secretion of H+, in excess of its capacity to react with HCO3- in the tubular lumenal fluid, requires the presence of other buffers (see below). The generation of HCO3- and H+ occurs by dissociation of carbonic acid (H2CO3), formed in the tubule cells from H2O and CO2, through the action of carbonic anhydrase. Secretion of H+ into the lumen of the tubule is accompanied by an exchange for Na+. This reabsorption of Na+ occurs by an antiport mechanism during the exchange for H+. Reduction in the intracellular concentration of Na+ occurs by an active transport process involving a Na+/K+-ATPase pump which pumps the excess Na+ into the interstitial fluid. The intracellular HCO3- then diffuses from the tubule cell into the interstitial fluid.
The capacity of the kidney to secrete H+ is regulated by the maximal H+ gradient that can form between the tubule and lumen and still allow transport mechanisms to operate. This gradient is determined by the pH of the urine which in humans is near 4.5. The capacity to secrete H+ would be rapidly reached if it were not for the presence of buffers within the interstitial fluid. The H+ secreted into the tubular lumen can undergo three different fates depending upon the concentration of the three primary buffers of the interstitial fluid. These buffers are HCO3-, HPO42- and NH3. Reaction of H+ with HCO3- forms H2O and CO2 which diffuse back into the tubule cell. The net result of this process is the regeneration of HCO3- within the tubule cell. This process is termed reabsorption of sodium bicarbonate. The reabsorption of sodium bicarbonate takes place primarily within the proximal convoluted tubules.

Excretion of Acid
As the concentration of HCO3- in the tubular lumen drops, the pH of the fluid drops due to an increasing concentration of H+. The pH of the tubular fluid gradually approaches the pKa for the dibasic/monobasic phosphate buffering system (pKa = 6.8). The excess H+ reacts with dibasic phosphate (HPO42-) forming monobasic phosphate (H2PO4-). The H2PO4- so formed is not reabsorbed and its excretion results in the net excretion of H+. The greatest extent of H2PO4- formation occurs within the distal convoluted tubules and the collecting ducts.



Buffering of H+ is also accomplished by reaction with ammonia, NH3, to form ammonium ion, NH4+. Elimination of NH4+ is the major contributory factor in the ability of the body to excrete acid. Because the pKa of NH4+ is 9.3, excretion of acid in this form can be accomplished without lowering the pH of the urine. Additionally important is the fact that excretion of acid in the form of NH4+ occurs without depleting Na+ nor K+.
Two principal reactions within tubule cells result in the generation of NH3, conversion of glutamine to glutamate and conversion of glutamate to -ketoglutarate. These reactions are catalyzed by glutaminase and glutamate dehydrogenase, respectively (Equations 21 and 22).

Glutamine ----> Glutamate + NH4+ Eqn. 21

Glutamate ----> -Ketoglutarate + NH4+ Eqn. 22

Both of these enzymes are abundant in tubule cells. Ammonia is lipid soluble and will diffuse down its concentration gradient out of the tubule cell into the tubular fluid. There it reacts with H+ to yield NH4+ which is excreted
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INTRODUCTION TO BIOCHEMISTRY


The study of the chemical substances and vital processes occurring in living organisms.
The chemical composition of a particular living system or biological substance.
Biochemistry is the application of chemistry to the study of biological processes at the cellular and molecular level. It emerged as a distinct discipline around the beginning of the 20th century when scientists combined chemistry, physiology and biology to investigate the chemistry of living systems.
Biochemistry has become the foundation for understanding all biological processes. It has provided explanations for the causes of many diseases in humans, animals and plants. It can frequently suggest ways by which such diseases may be treated or cured.
Biochemists study how living organisms extract food and energy from their environment and how they use the extracted molecules to make more of themselves. Buchner, by taking apart yeast cells, had opened the way to ask biochemical questions like: What kinds of molecules cause fermentation? How many different molecules are necessary? Why does the yeast cell do it? Why does it only happen if you keep oxygen out? These are questions that can be answered by separating the "dissolved substances" in the "juice" and asking what they are, how they interact with each other, and how their properties are related to their chemical nature.By using this approach, biochemists have succeeded in...Discovering that although too much cholesterol can cause heart disease, our bodies make cholesterol because it is an essential component of the membranes of our cells.Finding that cells distinctively mark themselves by putting specific groups of sugars, linked together in recognizable patterns, on their surfaces. Your body will reject transplanted tissue if the cells of that tissue have the wrong pattern of sugar groups on their surfaces.Learning that one of the reasons plants require the mineral nutrient magnesium is because it forms part of the structure of chlorophyll, the molecule plants use to trap solar energy.Exploring the way penicillin kills bacteria to discover that it prevents them from putting together the chemical structure of their cell walls.
Biochemistry focuses on the study of life at molecular level - how genes and proteins regulate cells, tissues, organs and ultimately whole organisms like you. As you go about your daily life biochemistry is sure to be involved. It has a role in:
understanding the causes of diseases;
use of engineered therapeutic proteins in medicine;
food production;
understanding how cells function.
This means you can see the effects of biochemistry all around you!
It is central to all areas of the Biological or Life Sciences. The aim is to provide an understanding of every aspect of the structure and function of living things at the molecular level. It is a practical laboratory science that applies the molecular approaches of chemistry to the vast variety of biological systems.Biochemists work at all levels and with all types of biological organisms, ranging from biomolecules to man. There are close links with other specialist life sciences, such as Cell Biology, Genetics, Microbiology, Molecular Biology, Physiology and Pharmacology. In fact, in many cases the distinctions between these disciplines are becoming increasingly blurred. They use biochemical techniques and biochemists work in all these areas. Biochemistry offers the tremendous challenge of seeking to understand the most fundamental of life's processes at the molecular level, and to utilise this knowledge for the benefit of mankind. You will have read, for example, how biochemists, working with colleagues in other disciplines, have developed the new technologies of Molecular Biology and Genetic Engineering. These have enabled the production of therapeutically important human proteins such as insulin and blood clotting factors by cloning procedures, thus avoiding costly, time-consuming and inefficient isolation of these molecules from biological sources; the identification and possible remedying of genetic problems; and the use of DNA fingerprinting in forensic science.
Biochemistry is the study of chemical processes associated with living organisms. Biochemists use concepts of biology, chemistry, physics, mathematics, microbiology, and genetics to unravel the complex puzzles of life. Biochemical techniques are used in clinical diagnosis of infectious diseases, genetic disorders, and cancer; as well as in many forms of research to improve the quality of our lives.

Biochemists identify biological problems then develop and apply appropriate techniques to solve them at the molecular levelBiochemists study the most basic of life processes; for example, identifying the way in which DNA, which carries the genetic information, is transferred between cells and can be manipulated. This has led to the development of new technologies such as Molecular Biology and Genetic Engineering. The resulting recombinant DNA technology has formed the basis of modern biotechnology (e.g. production of human insulin), medical developments (e.g. prenatal diagnosis and genetic counselling) and forensic science (e.g. DNA fingerprinting).DNA directs the production of proteins. These have diverse functions, such as catalysing biological reactions (enzymes), carrying oxygen round the body (haemoglobin), protecting us from infection (antibodies) and holding us together (collagen). Using both simple and high-technology methods, biochemists work out how these proteins function. Biochemists also develop methods for making use of proteins, such as enzymes in biotechnology and antibodies in hormone analysis.With knowledge of the basic molecular mechanisms, biochemists study how life processes are integrated to allow individual cells to function and interact to form complex organisms. They work with all sorts of organisms, from viruses and bacteria to plants and man.These are just a few of the areas. It would take a whole book, in fact many books, to do justice to the multitude of roles of biochemists.
Biochemists work in many walks of life - in industry, hospitals, agriculture, research institutes, education and associated areas. There are many areas of everyday life as diverse as medical products and diagnostics, new food and its safety, crop improvement, cosmetics and forensic science that owe their development or even existence to biochemists
IndustryPharmaceutical, food, brewing, biotechnology and agrochemical companies all need and employ biochemists to develop new products and to monitor the production, quality control and safety of existing ones.
MedicineHospitals, public health laboratories and medical research institutes, as well as the pharmaceutical industry, all require biochemists. Here they provide a diagnostic service, carrying out tests on blood, urine and other body fluids, alongside researching the underlying causes of disease and the methods of treatment.
Agriculture and the EnvironmentBiochemists and biotechnologists, who often have a biochemistry degree, working in agriculture have been responsible for many developments, such as pest-resistant crops, improvements in crop yields and tomatoes that keep better. They also monitor the environment. Employers include seed companies, local government, the Civil Service and water authorities.
EducationAll levels of education offer prospects for biochemists. The combination of biology and chemistry, along with the training in numerical and analytical skills that is given in any area of science, makes biochemistry ideal for teaching throughout the school age range. There are also opportunities for more advanced teaching, usually associated with research, in universities and colleges, and medical, dental and veterinary schools.
Away from ScienceA science background can be an excellent starting point for many other careers. Biochemistry is a numerate subject that develops analytical thinking, creativity in problem solving, and the ability to handle large amounts of complex information - skills required in jobs in all walks of life including, for example, sales and marketing, accountancy and finance, journalism, and patent work. Biochemists have become successful popular authors and even a national president!


Originally, it was generally believed that life was not subject to the laws of science the way non-life was. It was thought that only living beings could produce the molecules of life (from other, previously existing biomolecules). Then, in 1828, Friedrich Wöhler published a paper about the synthesis of urea, proving that organic compounds can be created artificially. The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term “biochemistry” seems to have been first used in 1881, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuber, a German chemist. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle).
Today, the findings of biochemistry are used in many areas, from genetics to molecular biology and from agriculture to medicine
macromolecule is a large molecule with a large molecular mass, but generally the use of the term is restricted to polymers and molecules which structurally include polymers. [

Illustration of a polypeptide macromolecule
Many examples come from biology and in particular biochemistry. In case of "biomacromolecules" or biopolymers, there are proteins, carbohydrates and nucleic acids (such as DNA). Lipids (fat) are not considered true macromolecules by most biologists as they are not covalently bonded, and so are not true polymers. Synthetic examples include plastics. The integral domains of crystals and metals, while composed of very large numbers of atoms joined by molecule-like bonds, are rarely referred to as "macromolecules."
The term macromolecule is also sometimes used to refer to aggregates of two or more macromolecules held together by intermolecular forces rather than by chemical "bonds". This usage is common in particular when the individual macromolecules involved aggregate or "assemble" spontaneously and rarely exist in isolation. Such an aggregate is more properly called a macromolecular complex. In such a context, individual macromolecules are often referred to as subunits (see e.g. protein subunit).
Substances that are composed of macromolecules often have unusual physical properties. The properties of liquid crystals and such elastomers as rubber are examples. Although too small to see, individual pieces of DNA in solution can be broken in two simply by suctioning the solution through an ordinary straw. This is not true of smaller molecules. The 1964 edition of Linus Pauling's College Chemistry asserted that DNA in nature is never longer than about 5000 base pairs. This is because biochemists were inadvertently and with perfect consistency breaking their samples into pieces. In fact, the DNA of chromosomes can be tens of millions of base pairs long.
Another common macromolecular property that does not characterize smaller molecules is the need for assistance in dissolving into solution. Many require salts or particular ions to dissolve in water. Proteins will denature if the solute concentration of their solution is too high or too low.
According to IUPAC recommendations the term macromolecule is reserved for an individual molecule, and the term polymer is used as to denote a substance composed of macromolecules. Polymer may also be employed unambiguously as an adjective, according to accepted usage, e.g. polymer blend, polymer molecule. [2]
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Major categories of bio-compounds:
Carbohydrates : sugar -- disaccharide -- polysaccharide -- cholesterol -- starch -- glycogen
Lipids : fatty acid -- fats -- essential oils -- oils -- waxes
Nucleic acids : DNA -- RNA -- mRNA -- tRNA -- rRNA -- codon -- adenosine -- cytosine -- guanine -- thymine -- uracil
Proteins :
amino acid -- glycine -- arginine -- lysine
peptide -- primary structure -- secondary structure -- tertiary structure -- conformation -- protein folding
Chemical properties:
molecular bond -- covalent bond -- ionic bond -- hydrogen bond -- ester -- ethyl
molecular charge -- hydrophilic -- hydrophobic -- polar
pH -- acid -- alkaline -- base
oxidation -- reduction -- hydrolysis
Structural compounds:
In cells: flagellin -- peptidoglycan -- myelin -- actin -- myosin
In animals: chitin -- keratin -- collagen -- silk
In plants: cellulose -- lignin -- cell wall
Enzymes and enzyme activity:
enzyme kinetics -- enzyme inhibition
proteolysis -- ubiquitin -- proteasome
kinase -- dehydrogenase
Membranes : fluid mosaic model -- diffusion -- osmosis
phospholipids -- glycolipid -- glycocalyx -- antigen -- isoprene
ion channel -- proton pump -- electron transport -- ion gradient -- antiporter -- symporter -- quinone -- riboflavin
Energy pathways :
pigments : chlorophyll -- carotenoids -- xanthophyll -- cytochrome -- phycobilin -- bacteriorhodopsin -- hemoglobin -- myoglobin -- absorption spectrum -- action spectrum -- fluorescence
Photosynthesis : light reaction -- dark reaction
Fermentation : Acetyl-CoA -- lactic acid
Cellular respiration : Adenosine triphosphate (ATP) -- NADH -- pyruvate -- oxalate -- citrate
Chemosynthesis
Regulation
hormones : auxin
signal transduction -- growth factor -- transcription factor -- protein kinase -- SH3 domain
Malfunctions : tumor -- oncogene -- tumor suppressor gene
Receptors : Integrin -- transmembrane receptor -- ion channel
Techniques : electrophoresis -- chromatography -- mass spectrometry -- x-ray diffraction -- Southern blot -- fractionation -- Gram stain
Objective
To describe functional groups of organic compounds of biological interest and provide some examples of chemical reactions and interconversions among these. Reference: Stryer, 4th edition, 1994, Chapter 1, pp. 3-16
I. Some Examples of Chemical Reactions
I. Functional Groups a. Alcohols R-CH2-OH(primary); R2-CH-OH (secondary); R3-C-OH (tertiary) Sustitution on the Carbon atom defines whether the alcohol is primary, secondary or tertiary. Carbon atom in these cases is in sp3 hybrid state.
b. Aldehydes and Ketones
R-CHO; R2-C=O
Carbon atom is double bonded to oxygen in both cases. The difference is in substitutions. Aldehyde has an R group and a H atom whereas in a ketone both substituents are R groups. Carbon atom in these cases is in sp2 hybrid state.
c. Acids R-C=O Acids are able to dissociate into H+ and anions ! OH d. Acid Anhydrides
(R-CO)2O Acid anhydrides are formed from molecules of same or different acids with the elimination of a molecule of water. An example would the formation of pyrophosphate from two molecules of phosphoric acid.
e. Esters
RCH2-O-COCH3
An ester is formed from an alcohol and an acid with the elimination of a molecule of water.Physiological examples include formation of triacyl glycerols from fatty acids and glycerol.
f. Unsaturated Compounds
Unsaturated compouds like R-CH=CH---- are formed either by the elimination of water fron a hydroxy compund like R-CHOH-CH2---- or by dehydrogenation of compunds like R-CH2-CH2---. The double bond may be cis or trans depending on the positions of hydrogen atoms in space. In cis configuration, H atoms would lie in a plane perpendicular to the plane of the double bond whereas iin trans configuration H atoms lie in the same plane as the double bond.
g. Amines and Amides II. Reaction Types A. Oxidation/Reduction (removal of electron or reaction with O2) B. Esterification (carboxylic acid plus alcohol) C. Hydrolysis (cleavage of a bond by water) D. Phosphorolysis (cleavage of a bond by inorganic phosphate) E. Decarboxylation F. Deamination G. Transamination (amino group transfer) H. Phosphorylation (ester bond on sugars, some amino acids, bases) I. Dehydration J. Phosphorylation (transfer of a phosphate group) K. Transmethylation L. Condensation III. Coupled Reactions Decarboxylation and oxidation/reduction
Study Assignment I Draw the structures of molecules that have the functional groups listed above and identify the functional groups. Some molecules will have several functional groups. Study Assignment II For reaction types listed in IIA-L, above, write out the entire reaction, including molecular structure. Use material presented to you in Biochemistry lectures to complete the assignment.

CARBOHYDRATE METABOLISM

THE CARBOHYDRATE MThe function of carbohydrates includes energy storage and providing structure. Sugars are carbohydrates, although there are carbohydrates that are not sugars. There are more carbohydrates on Earth than any other type of biomolecule. The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOnETA

CARBOHYDRATE CHEMISTRY

The function of carbohydrates includes energy storage and providing structure. Sugars are carbohydrates, although there are carbohydrates that are not sugars. There are more carbohydrates on Earth than any other type of biomolecule. The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOn, where n is at least 3). Glucose, one of the most important carbohydrates, is an example of a monosaccharide. So is fructose, the sugar that gives fruits their sweet taste. Some carbohydrates (especially after condensation to oligo- and polysaccharides) contain less carbon relative to H and O, which still are present in 2:1 (H:O) ratio. Monosaccharides can be grouped into aldoses (having an aldehyde group at the end of the chain, e. g. glucose) and ketoses (having a keto group in their chain; e. g. fructose). Both aldoses and ketoses occur in an equilibrium between the open-chain forms and (starting with chain lengths of C4) cyclic forms. These are generated by bond formation between one of the hydroxy groups of the sugar chain with the carbon of the aldehyde or keto group in a semiacetal bond. This leads to saturated five-membered (in furanoses) or six-membered (in pyranoses) heterocyclic rings containing one O as heteroatom.
Two monosaccharides can be joined together using dehydration synthesis, in which a hydrogen atom is removed from the end of one molecule and a hydroxyl group (—OH) is removed from the other; the remaining residues are then attached at the sites from which the atoms were removed. The H—OH or H2O is then released as a molecule of water, hence the term dehydration. The new molecule, consisting of two monosaccharides, is called a disaccharide and is conjoined together by a glycosidic or ether bond. The reverse reaction can also occur, using a molecule of water to split up a disaccharide and break the glycosidic bond; this is termed hydrolysis. The most well-known disaccharide is sucrose, ordinary sugar (in scientific contexts, called table sugar or cane sugar to differentiate it from other sugars). Sucrose consists of a glucose molecule and a fructose molecule joined together. Another important disaccharide is lactose, consisting of a glucose molecule and a galactose molecule. As most humans age, the production of lactase, the enzyme that hydrolyzes lactose back into glucose and galactose, typically decreases. This results in lactase deficiency, also called lactose intolerance.
Sugar polymers are characterised by having reducing or non-reducing ends. A reducing end of a carbohydrate is a carbon atom which can be in equilibrium with the open-chain aldehyde or keto form. If the joining of monomers takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an OH-side chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety form a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).
When a few (around three to six) monosaccharides are joined together, it is called an oligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers and signals, as well as having some other uses.
Many monosaccharides joined together make a polysaccharide. They can be joined together in one long linear chain, or they may be branched. Two of the most common polysaccharides are cellulose and glycogen, both consisting of repeating glucose monomers. Cellulose is made by plants and is an important structural component of their cell walls. Humans can neither manufacture nor digest it. Glycogen, on the other hand, is an animal carbohydrate; humans use it as a form of energy storage.
Glucose is the major energy source in most life forms; a number of catabolic pathways converge on glucose. For instance, polysaccharides are broken down into their monomers (glycogen phosphorylase removes glucose residues from glycogen). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides. Glucose is mainly metabolized by a very important and ancient ten-step pathway called glycolysis, the net result of which is to break down one molecule of glucose into two molecules of pyruvate; this also produces a net two molecules of ATP, the energy currency of cells, along with two reducing equivalents in the form of converting NAD+ to NADH. This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate to lactate (e. g. in humans) or to ethanol plus carbon dioxide (e. g. in yeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway. In aerobic cells with sufficient oxygen, like most human cells, the pyruvate is further metabolized. It is irreversibly converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric acid cycle, producing two more molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via FADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thereby, oxygen is reduced to water and the original electron acceptors NAD+ and quinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional 28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle). It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of oxygen.
In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate (lactic acid). The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides.
Carbohydrates are molecules that contain oxygen, hydrogen, and carbon atoms. They may also contain other elements such as sulfur or nitrogen, but these are usually minor components. They consist of monosaccharide sugars, of varying chain lengths, that have the general chemical formula Cn(H2O)n or are derivatives of such.The smallest value for n is 3. A 3-carbon sugar is referred to as a triose, whereas a 6-carbon sugar is called a hexose (see monosaccharides below). Certain carbohydrates are important for storing and transporting energy in most organisms, including plants and animals, and are major structural elements in many organisms (eg cellulose in plants). In addition they play major roles in cell to cell communication, the immune system, fertilization, pathogenesis, blood clotting, and development. Carbohydrates can be classified by the number of constituent sugar units: monosaccharides (such as glucose and fructose), disaccharides (such as sucrose and lactose), oligosaccharides, and polysaccharides (such as starch, glycogen, and cellulose).


Glucose as a straight-chain carbohydrate (Fischer projection)


Fructose (Fischer projection)
Pure carbohydrates contain carbon, hydrogen, and oxygen atoms, in a 1:2:1 molar ratio, giving the general formula Cn(H2O)n. (This applies only to monosaccharides, see below, although all carbohydrates have the more general formula Cn(H2O)m.) However, many important carbohydrates deviate from this, such as deoxyribose and glycerol. Sometimes compounds containing other elements are also counted as carbohydrates (e.g. glucosamine and chitin, which contain nitrogen).
The simplest carbohydrates are monosaccharides, which are small straight-chain aldehydes and ketones with many hydroxyl groups added, usually one on each carbon except the functional group. Other carbohydrates are composed of monosaccharide units and break down under hydrolysis. These may be classified as disaccharides, oligosaccharides, or polysaccharides, depending on whether they have two, several, or many monosaccharide units.
Monosaccharides
Monosaccharides may be divided into aldoses, which have an aldehyde group on the first carbon atom, and ketoses, which typically have a ketone group on the second. They may also be divided into trioses, tetroses, pentoses, hexoses,and many more. This all depends on how many carbon atoms they contain. For instance, glucose is an aldohexose, fructose a ketohexose, and ribose an aldopentose.
Further, each carbon atom that supports a hydroxyl group (except for the first and last) is a stereogenic centre, allowing a number of different enantiomers and stereoisomers for carbohydrates with the same basic structure. For instance, galactose is an aldohexose but has different properties from glucose because the atoms are arranged differently.
A heterocyclic form of ribose (Haworth projection)
The straight-chain structure described here is only one of the forms a monosaccharide may take. The aldehyde or ketone group may react with a hydroxyl group on a different carbon atom to form a hemiacetal or hemiketal, in which case there is an oxygen bridge between the two carbon atoms, forming a heterocyclic ring. Rings with five and six atoms are called furanose and pyranose forms and exist in equilibrium with the straight-chain form.
It should be noted that the ring form has one more stereogenic centre than the straight-chain form, and so has both an alpha and a beta form, which interconvert in equilibrium. However, the carbohydrate may further react with an alcohol to form an acetal or ketal, in which case the two forms become distinct. This is the basic type of link between the monosaccharide units of larger carbohydrates. Excessive consumption may cause obesity.
An aldose is a monosaccharide (a certain type of sugar) containing one aldehyde group per molecule and having a chemical formula of the form CnH2nOn (n>=3).
Triose: glyceraldehyde
Tetroses: erythrose, threose
Pentoses: ribose, arabinose, xylose, lyxose
Hexoses: allose, altrose, glucose, mannose, gulose, idose, galactose, talose

With only 3 carbon atoms, glyceraldehyde is the simplest of all aldoses.
Aldoses isomerize to ketoses in the Lobry-de Bruyn-van Ekenstein transformation
An aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom which is bonded to a hydrogen atom and double-bonded to an oxygen atom (chemical formula -CHO), is called the aldehyde group. The aldehyde group is also called the formyl or methanoyl group.
The word aldehyde seems to have arisen from alcohol dehydrogenated. In the past, aldehydes were sometimes named after the corresponding alcohols, for example vinous aldehyde for acetaldehyde. (Vinous is from Latin vinum = wine, the traditional source of ethanol; compare vinyl.)
The aldehyde group is polar. Oxygen, being more electronegative, pulls the electrons in the carbon-oxygen bond towards itself, thus creating an electron deficiency at the carbon atom.


Disaccharides

Disaccharides are composed of two monosaccharide units bound together by a covalent glycosidic bond. The binding between the two sugars results in the loss of a hydrogen atom (H) from one molecule and a hydroxyl group (OH) from the other.
The most common disaccharides are sucrose (cane or beet sugar - made from one glucose and one fructose), lactose (milk sugar - made from one glucose and one galactose), maltose (made of two glucoses linked alpha-1,4) and cellobiose (made of two glucoses linked beta-1,4). The formula of these disaccharides is C12H22O11.
Other examples of disaccharides include trehalose, chitobiose, laminaribiose, kojibiose and xylobiose.











Oligosaccharides and polysaccharides
Main articles: Oligosaccharide and Polysaccharide
Oligosaccharides and polysaccharides are composed of longer chains of monosaccharide units bound together by glycosidic bonds. The distinction between the two is based upon the number of monosaccharide units present in the chain. Oligosaccharides typically contain between two and nine monosaccharide units, and polysaccharides contain greater than ten monosaccharide units. Definitions of how large a carbohydrate must be to fall into each category vary according to personal opinion. Examples of oligosaccharides include the disaccharides mentioned above, the trisaccharide raffinose and the tetrasaccharide stachyose.
Oligosaccharides are found as a common form of protein posttranslational modification. Such posttranslational modifications include the Lewis oligosaccharides responsible for blood group incompatibilities, the alpha-Gal epitope responsible for hyperacute rejection in xenotransplanation, and O-GlcNAc modifications.
Polysaccharides represent an important class of biological polymer. Examples include starch, cellulose, chitin, glycogen, callose, laminarin, xylan, and galactomannan.