Which amino acids are most likely to be found in the interior core region of a protein?
Source: BiochemFFA_2_1.pdf. The entire textbook is available for free from the authors at
http://biochem.science.oregonstate.edu/content/biochemistry-free-and-easy All of the proteins on the face of the earth are made up of the same 20 amino acids. Linked together in long chains called polypeptides, amino acids are the building blocks for the vast assortment of proteins
found in all living cells. "It is one of the more striking generalizations of biochemistry ...that the twenty amino acids and the four bases, are, with minor reservations, the same throughout Nature." - Francis Crick All amino acids have the same basic
structure, which is shown in Figure 2.1. At the “center” of each amino acid is a carbon called the α carbon and attached to it are four groups - a hydrogen, an α- carboxyl group, an α-amine group, and an R-group, sometimes referred to as a side chain. The α carbon, carboxyl, and amino groups are common to all amino acids, so the R-group is the only unique feature in each amino acid. (A minor exception to this structure is that of proline, in which the end of the R-group is attached to the
α-amine.) With the exception of glycine, which has an R-group consisting of a hydrogen atom, all of the amino acids in proteins have four different groups attached to them and consequently can exist in two mirror image forms, L and D. With only very minor exceptions, every amino acid found in cells and in proteins is in the L configuration. There are 22 amino acids that are found in proteins and of these, only 20 are specified by the universal genetic code. The others, selenocysteine and pyrrolysine use tRNAs that are able to base pair with stop codons in the mRNA during translation. When
this happens, these unusual amino acids can be incorporated into proteins. Enzymes containing selenocysteine, for example, include glutathione peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, and selenophosphate synthetase. Pyrrolysine-containing proteins are much rarer and are mostly confined to archaea. Nutritionists divide amino acids into two groups - essential amino acids (must be in the diet because cells can’t synthesize them) and non-essential amino acids (can be made by cells). This classification of amino acids has little to do with the structure of amino acids.
Essential amino acids vary considerable from one organism to another and even differ in humans, depending on whether they are adults or children. Table 2.1 shows essential and non-essential amino acids in humans. Some amino acids that are normally nonessential, may need to be obtained from the diet in certain cases. Individuals who do not synthesize sufficient amounts of arginine, cysteine, glutamine, proline, selenocysteine, serine, and tyrosine, due to illness, for example, may need
dietary supplements containing these amino acids. Table 2.1 - Essential and non-essential amino acids Non-protein amino acids There are also α-amino acids found in cells that are not incorporated into proteins. Common ones include ornithine and citrulline. Both of these compounds are intermediates in the urea cycle. Ornithine is a metabolic precursor of arginine and citrulline can be produced by the breakdown of arginine. The latter reaction produces nitric oxide, an important signaling molecule. Citrulline is the metabolic byproduct. It is sometimes used as a dietary supplement to reduce muscle fatigue. R-group chemistry Table 2.2 - Amino acid categories (based on R-group properties) We separate the amino acids into categories based on the chemistry of their R-groups. If you compare groupings of amino acids in different textbooks, you will see different names for the categories and (sometimes) the same amino acid being categorized differently by different authors. Indeed, we categorize tyrosine both as an aromatic amino acid and as a hydroxyl amino acid. It is useful to classify amino acids based on their R-groups, because it is these side chains that give each amino acid its characteristic properties. Thus, amino acids with (chemically) similar side groups can be expected to function in similar ways, for example, during protein folding. Non-polar amino acids
Carboxyl Amino Acids
Amine amino acids
Aromatic amino acidsFigure 2.6 - Aromatic amino acids
Hydroxyl amino acids
Tyrosine - see HERE. Figure 2.8 - Amino acid properties WikipediaOther amino acids
Ionizing groupspKa values for amino acid side chains are very dependent upon the chemical environment in which they are present. For example, the R-group carboxyl found in aspartic acid has a pKa value of 3.9 when free in solution, but can be as high as 14 when in certain environments inside of proteins, though that is unusual and extreme. Each amino acid has at least one ionizable amine group (α- amine) and one ionizable carboxyl group (α- carboxyl). When these are bound in a peptide bond, they no longer ionize. Some, but not all amino acids have R-groups that can ionize. The charge of a protein then arises from the charges of the α-amine group, the α- carboxyl group. and the sum of the charges of the ionized R-groups. Titration/ionization of aspartic acid is depicted in Figure 2.10. Ionization (or deionization) within a protein’s structure can have significant effect on the overall conformation of the protein and, since structure is related to function, a major impact on the activity of a protein. Figure 2.10 - Titration curve for aspartic acid Image by Penelope IrvingMost proteins have relatively narrow ranges of optimal activity that typically correspond to the environments in which they are found (Figure 2.11). It is worth noting that formation of peptide bonds between amino acids removes ionizable hydrogens from both the α- amine and α- carboxyl groups of amino acids. Thus, ionization/ deionization in a protein arises only from 1) the amino terminus; 2) carboxyl terminus; 3) R-groups; or 4) other functional groups (such as sulfates or phosphates) added to amino acids post-translationally - see below. CarnitineNot all amino acids in a cell are found in proteins. The most common examples include ornithine (arginine metabolism), citrulline (urea cycle), and carnitine (Figure 2.12). When fatty acids destined for oxidation are moved into the mitochondrion for that purpose, they travel across the inner membrane attached to carnitine. Of the two stereoisomeric forms, the L form is the active one. The molecule is synthesized in the liver from lysine and methionine. Figure 2.12 - L-CarnitineFrom exogenous sources, fatty acids must be activated upon entry into the cytoplasm by being joined to coenzyme A. The CoA portion of the molecule is replaced by carnitine in the intermembrane space of the mitochondrion in a reaction catalyzed by carnitine acyltransferase I. The resulting acylcarnitine molecule is transferred across the inner mitochondrial membrane by the carnitineacylcarnitine translocase and then in the matrix of the mitochondrion, carnitine acyltransferase II replaces the carnitine with coenzyme A (Figure 6.88). Figure 2.11 - Enzyme activity changes as pH changes Image by Aleia KimCatabolism of amino acidsWe categorize amino acids as essential or non-essential based on whether or not an organism can synthesize them. All of the amino acids, however, can be broken down by all organisms. They are, in fact, a source of energy for cells, particularly during times of starvation or for people on diets containing very low amounts of carbohydrate. From a perspective of breakdown (catabolism), amino acids are categorized as glucogenic if they produce intermediates that can be made into glucose or ketogenic if their intermediates are made into acetyl-CoA. Figure 2.13 shows the metabolic fates of catabolism of each of the amino acids. Note that some amino acids are both glucogenic and ketogenic. Figure 2.13 - Catabolism of amino acids. Some have more than one path. Image by Pehr JacobsonPost-translational modifications After a protein is synthesized, amino acid side chains within it can be chemically modified, giving rise to more diversity of structure and function (Figure 2.14). Common alterations include phosphorylation of hydroxyl groups of serine, threonine, or tyrosine. Lysine, proline, and histidine can have hydroxyls added to amines in their R-groups. Other modifications to amino acids in proteins include addition of fatty acids (myristic acid or palmitic acid), isoprenoid groups, acetyl groups, methyl groups, iodine, carboxyl groups, or sulfates. These can have the effects of ionization (addition of phosphates/sulfates), deionization (addition of acetyl group to the R-group amine of lysine), or have no effect on charge at all. In addition, N-linked- and O-linkedglycoproteins have carbohydrates covalently attached to side chains of asparagine and threonine or serine, respectively. Some amino acids are precursors of important compounds in the body. Examples include epinephrine, thyroid hormones, Ldopa, and dopamine (all from tyrosine), serotonin (from tryptophan), and histamine (from histidine). Figure 2.14 - Post-translationally modified amino acids. Modifications shown in green. Image by Penelope Irving Figure 2.15 - Phosphorylated amino acidsBuilding PolypeptidesAlthough amino acids serve other functions in cells, their most important role is as constituents of proteins. Proteins, as we noted earlier, are polymers of amino acids. Amino acids are linked to each other by peptide bonds, in which the carboxyl group of one amino acid is joined to the amino group of the next, with the loss of a molecule of water. Additional amino acids are added in the same way, by formation of peptide bonds between the free carboxyl on the end of the growing chain and the amino group of the next amino acid in the sequence. A chain made up of just a few amino acids linked together is called an oligopeptide (oligo=few) while a typical protein, which is made up of many amino acids is called a polypeptide (poly=many). The end of the peptide that has a free amino group is called the N-terminus (for NH2), while the end with the free carboxyl is termed the C-terminus (for carboxyl). Figure 2.16 Formation of a peptide bondAs we’ve noted before, function is dependent on structure, and the string of amino acids must fold into a specific 3-D shape, or conformation, in order to make a functional protein. The folding of polypeptides into their functional forms is the topic of the next section. Which amino acids are found in the interior of a protein?In a protein, hydrophobic amino acids are likely to be found in the interior, whereas hydrophilic amino acids are likely to be in contact with the aqueous environment.
Which type of amino acids are more likely to be found on the interior of a globular protein that exists in the cytosol of the cell?Hydrophobic, non-polar amino acids play an essential role in protein folding because they tend to draw together and clump away from water. These amino acids usually form transmembrane domains and are found deeply buried in the hydrophobic interior of most globular proteins.
Which of the following amino acids would be most likely to be found on the interior of a folded protein?Introduction to Biochemistry
Out of the given AAs in the question, Asp (aspartic acid) is the polar one, and thus, it is most likely to be found on the protein's surface. Hence, the correct option is (C). The hydrophobic (water-repelling) amino acids are the ones that are usually found in the protein's interior.
What types of amino acids would you most expect to find in this interior region?Polar and charged amino acid residues (the remainder after peptide bond formation) are more likely to be found on the surface of soluble proteins where they can interact with water, and nonpolar (e.g., amino acid side chains) are more likely to be found in the interior where they are sequestered from water.
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