All about amioacids

New a a Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. The 20 amino acids that are found within proteins convey a vast array of chemical versatility. The precise amino acid content, and the sequence of those amino acids, of a specific protein, is determined by the sequence of the bases in the gene that encodes that protein. The chemical properties of the amino acids of proteins determine the biological activity of the protein. Proteins not only catalyze all (or most) of the reactions in living cells, they control virtually all cellular process. In addition, proteins contain within their amino acid sequences the necessary information to determine how that protein will fold into a three dimensional structure, and the stability of the resulting structure. The field of protein folding and stability has been a critically important area of research for years, and remains today one of the great unsolved mysteries. It is, however, being actively investigated, and progress is being made every day. As we learn about amino acids, it is important to keep in mind that one of the more important reasons to understand amino acid structure and properties is to be able to understand protein structure and properties. We will see that the vastly complex characteristics of even a small, relatively simple, protein are a composite of the properties of the amino acids which comprise the protein. Humans can produce 10 of the 20 amino acids. The others must be supplied in the food. Failure to obtain enough of even 1 of the 10 essential amino acids, those that we cannot make, results in degradation of the body's proteins—muscle and so forth—to obtain the one amino acid that is needed. Unlike fat and starch, the human body does not store excess amino acids for later use—the amino acids must be in the food every day. The 10 amino acids that we can produce are alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine and tyrosine. Tyrosine is produced from phenylalanine, so if the diet is deficient in phenylalanine, tyrosine will be required as well. The essential amino acids are arginine (required for the young, but not for adults), histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These amino acids are required in the diet. Plants, of course, must be able to make all the amino acids. Humans, on the other hand, do not have all the the enzymes required for the biosynthesis of all of the amino acids. Why learn these structures and properties? Aliphatic Amino Acids Aliphatic R groups are nonpolar and hydrophobic. Hydrophobicity increases with increasing number of C atoms in the hydrocarbon chain. Although these amino acids prefer to remain inside protein molecules, alanine and glycine are ambivalent, meaning that they can be inside or outside the protein molecule. Glycine has such a small side chain that it does not have much effect on the hydrophobic interactions. The structures below are shown in the ionization state that predominates at pH 7. Less hydrophobic More hydrophobic Aromatic Amino Acids Aromatic amino acids are relatively nonpolar. To different degrees, all aromatic amino acids absorb ultraviolet light. Tyrosine and tryptophan absorb more than do phenylalanine; tryptophan is responsible for most of the absorbance of ultraviolet light (ca. 280 nm) by proteins. Tyrosine is the only one of the aromatic amino acids with an ionizable side chain. Tyrosine is one of three hydroxyl containing amino acids. Least hydrophobic Very hydrophobic Acidic Amino Acids and their Amides Acidic amino acids are polar and negatively charged at physiological pH. Both acidic amino acids have a second carboxyl group. Amides are polar and uncharged, and not ionizable. All are very hydrophilic. Acidic amino acid Amide Acidic amino acid Amide Basic Amino Acids Basic amino acids are polar and positively charged at pH values below their pKa's, and are very hydrophilic. Even though the basic amino acids are almost always in contact with the solvent, the side chain of lysine has a marked hydrocarbon character, so it is often found NEAR the surface, with the amino group of the side chain in contact with solvent. Note that in the drawing, histidine is shown in the protonated form, while at pH 7.0, the imidazole would exist predominantly in the neutral form. Cyclic Amino Acid Proline is the only cyclic amino acid. It is nonpolar and shares many properties with the aliphatic group. Proline is one of the ambivalent amino acids, meaning that it can be inside or outside of a protein molecule. Due to its unique structure, proline occurs in proteins frequently in turns or bends, which are often on the surface. The structure shown is of the amino acid in the ionization state that predominates at pH 7.0. Hydroxyl Amino Acids Hydroxyl amino acids are polar, uncharged at physiological pH, and hydrophilic. The phenolic hydroxyl ionizes with a pKa of 10 to yield the phenolate anion. The hydroxyl groups of serine and threonine are so high that they are generally regarded as nonionizing. Sulfur-Containing Amino Acids The sulfur-containing amino acids (cysteine and methionine) are generally considered to be nonpolar and hydrophobic. In fact, methionine is one of the most hydrophobic amino acids and is almost always found on the interior of proteins. Cysteine on the other hand does ionize to yield the thiolate anion. Even so, it is uncommon to find cysteine on the surface of a protein. There are several reasons. First, sulfur has a low propensity to hydrogen bond, unlike oxygen. A consequence of this fact is that H2S is a gas under conditions that H2O is a liquid. Second, the thiol group of cysteine can react with other thiol groups in an oxidation reaction that yields a disulfide bond. Perhaps as a consequence, cysteine residues are most frequently buried inside proteins. Individua amino acids Alanine A (Ala) Chemical Properties: Aliphatic(Aliphatic R-group) Physical Properties: Nonpolar Alanine is a hydrophobic molecule. It is ambivalent, meaning that it can be inside or outside of the protein molecule. The α carbon of alanine is optically active; in proteins, only the L-isomer is found. Note that alanine is the α-amino acid analog of the α-keto acid pyruvate, an intermediate in sugar metabolism. Alanine and pyruvate are interchangeable by a transamination reaction. Interchangeable with Pyruvate Chemical Properties: Basic (Basic R-group) Physical Properties: Polar (positively charged) Arginine, an essential amino acid, has a positively charged guanidino group. Arginine is well designed to bind the phosphate anion, and is often found in the active centers of proteins that bind phosphorylated substrates. As a cation, arginine, as well as lysine, plays a role in maintaining the overall charge balance of a protein. Arginine also plays an important role in nitrogen metabolism. In the urea cycle, the enzyme arginase cleaves (hydrolyzes) the guanidinium group to yield urea and the L-amino acid ornithine. Ornithine is lysine with one fewer methylene groups in the side chain. L-ornithine is not normally found in proteins. There are 6 codons in the genetic code for arginine, yet, although this large a number of codons is normally associated with a high frequency of the particular amino acid in proteins, arginine is one of the least frequent amino acids. The discrepancy between the frequency of the amino acid in proteins and the number of codons is greater for arginine than for any other amino acid. Asparagine N (Asn) Chemical Properties: Neutral (Amides of acidic amino acids R-group) Physical Properties: Polar (uncharged) Asparagine is the amide of aspartic acid. The amide group does not carry a formal charge under any biologically relevant pH conditions. The amide is rather easily hydrolyzed, converting asparagine to aspartic acid. This process is thought to be one of the factors related to the molecular basis of aging. Asparagine has a high propensity to hydrogen bond, since the amide group can accept two and donate two hydrogen bonds. It is found on the surface as well as buried within proteins. Asparagine is a common site for attachment of carbohydrates in glycoproteins. Cysteine C (Cys) Chemical Properties: Sulfur-containing (Sulfur containing group) Physical Properties: Polar (uncharged) Cysteine is one of two sulfur-containing amino acids; the other is methionine. Cysteine differs from serine in a single atom-- the sulfur of the thiol replaces the oxygen of the alcohol. The amino acids are, however, much more different in their physical and chemical properties than their similarity might suggest. Consider, for example, the differences between H2O and H2S. The hydrogen bonding propensity of water is well known and is responsible for many of its remarkable features. Under similar conditions of temperature and pressure, however, H2S is a gas as a consequence of its weak H-bonding propensity. Furthermore, the proton of the thiol of cysteine is much more acid than the hydroxylic proton of serine, making the nucleophilic thiol(ate) much more reactive than the hydroxyl of serine. Cysteine also plays a key role in stabilizing extracellular proteins. Cysteine can react with itself to form an oxidized dimer by formation of a disulfide bond. The environment within a cell is too strongly reducing for disulfides to form, but in the extracellular environment, disulfides can form and play a key role in stabilizing many such proteins, such as the digestive enzymes of the small intestine. Cysteine and methionine are the only sulfur-containing amino acids. Glutamic Acid E (Glu) Chemical Properties: Acidic (Acidic R-group and their amides) Physical Properties: Polar (charged) Interconvertible with α-ketoglutarate Biosynthesis of Proline Glutamic acid has one additional methylene group in its side chain than does aspartic acid. The side chain carboxyl of aspartic acid is referred to as the β carboxyl group, while that of glutamic acid is referred to as the γ carboxyl group. The pKa of the γ carboxyl group for glutamic acid in a polypeptide is about 4.3, significantly higher than that of aspartic acid. This is due to the inductive effect of the additional methylene group. In some proteins, due to a vitamin K dependent carboxylase, some glutamic acids will be dicarboxylic acids, referred to as γ carboxyglutamic acid, that form tight binding sites for calcium ion. Glutamic acid is interconvertible by transamination withα-ketoglutarate Glutamic acid and α-ketoglutarate, an intermediate in the Krebs cycle, are interconvertible by transamination. Glutamic acid can therefore enter the Krebs cycle for energy metabolism, and be converted by the enzyme glutamine synthetase into glutamine, which is one of the key players in nitrogen metabolism. Biosynthesis of Proline Note also that glutamic acid is easily converted into proline. First, the γ carboxyl group is reduced to the aldehyde, yielding glutamate semialdehyde. The aldehyde then reacts with the α-amino group, eliminating water as it forms the Schiff base. In a second reduction step, the Schiff base is reduced, yielding proline.