Biosynthesis Of Nonessential Amino Acids PDF

Biochemistry Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids: Humans do not have the ability to synthesize 10 of the proteogenic am...

Biochemistry Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids: Humans do not have the ability to synthesize 10 of the proteogenic amino acids and must obtain them from the diet. These 10 are termed the nutritionally essential amino acids. The number of enzymes required by cells to synthesize the nutritionally essential amino acids is large in relation to the number of enzymes required to synthesize the nutritionally nonessential amino acids. This suggests that there is a positive survival advantage in retaining the ability to manufacture ‘easy’ amino acids while losing the ability to make ‘difficult’ amino acids. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Glutamate: Can be synthesized by transamination of the corresponding α -keto acid, α – ketoglutarate. The amino donor may be any amino acid (except lysine, threonine, proline hydroxylysine and hydroxyproline). Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Alanine: Transamination of pyruvate forms alanine. The amino donor may be glutamate or aspartate. The other product thus is α-ketoglutarate or oxaloacetate. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Aspartate: Can be synthesized by transamination of oxaloacetate to form aspartate and αketoglutarate. The amino donor is glutamate. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 1. Transamination: Serine: Is synthesized by the oxidation, transamination and subsequent dephosphorylation of 3-phosphogylcerate, an intermediate of glycolysis. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: Note: In all of the transamination reactions, pyridoxal phosphate PLP (vitamin B6) acts as an intermediate carrier of the amino group that is being transferred. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 2. Assimilation of Free Ammonia: Glutamate: Formation of glutamate from free ammonia and αketoglutarate is catalyzed by glutamate dehydrogenase. This reaction is reversible and plays a role in both synthesis and breakdown of glutamate. Both NADPH and NADH can serve as the source of reducing equivalents used in this reaction. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 2. Assimilation of Free Ammonia: Glutamine: Glutamine synthetase catalyzes the ATP-dependent formation of glutamine, using glutamate and ammonia as substrates. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Cysteine: Cysteine contains atoms donated by both methionine and serine. Following conversion of methionine to homocysteine, homocysteine and serine form cystathionine, a thioether (RSRʹ), the reaction is catalyzed by cystathionine β-synthase. Hydrolysis of cystathionine by cystathionine lyase forms cysteine. While cysteine is nutritionally nonessential, it is formed from methionine, which is nutritionally essential. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Cysteine: Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Glycine: Three mammalian routes for glycine formation. 1. From serine which is converted to glycine by the removal of its hydroxymethyl group. The reaction is freely reversible and catalyzed by serine hydroxymethyl transferase. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Glycine: Figure – Interconversion of serine and glycine, catalyzed by serine hydroxymethyltransferase (H4 folate: tetrahydrofolate, cofactor) Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Glycine: 2. From glyoxylate and glutamate or alanine catalyzed by glycine aminotransferase (irreversible, unlike other transamination reactions). Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Glycine: 3. From choline. Tyrosine: Phenylalanine is hydroxylated to form tyrosine a reaction catalyzed by phenylalanine hydroxylase. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Tyrosine: Note: Provided that the diet contains adequate nutritionally essential phenylalanine, tyrosine is nutritionally nonessential. Since the reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Proline: Glutamate is reduced and cyclized to form proline. Asparagine: Asparagine is synthesized from aspartate catalyzed by asparagine synthetase. Coupled hydrolysis of pyrophosphate (PPi) to Pi by pyrophosphatase ensures that the reaction is strongly favored. Note similarities to and differences from the glutamine synthetase reaction. Biosynthesis of Nonessential Amino Acids The 10 Nonessential Amino Acids are Formed by 3 General Mechanisms: 3. Modification of the Carbon Skeletons of Existing Amino Acids: Asparagine: L-Aspartate L-Asparagine L-Aspartate H2O + Gln Glu L-Aspartate Mg-ATP Mg-AMP + PPi Biosynthesis of Nonessential Amino Acids Hydroxyproline & Hydroxylysine: Hydroxyproline and hydroxylysine occur principally in collagen. Since there is no tRNA for either hydroxylated amino acid, neither dietary hydroxyproline nor dietary hydroxylysine is incorporated during protein synthesis. Peptidyl hydroxyproline and hydroxylysine arise from proline and lysine, but only after these amino acids have been incorporated into peptides. Hydroxylation of peptidyl prolyl and peptidyl lysyl residues, catalyzed by prolyl hydroxylase and lysyl hydroxylase of skin, skeletal muscle, and granulating wounds requires, in addition to the substrate, molecular O2 , ascorbate, Fe2+ , and α ketoglutarate. Biosynthesis of Nonessential Amino Acids Hydroxyproline & Hydroxylysine: For every mole of proline or lysine hydroxylated, one mole of α –ketoglutarate is decarboxylated to succinate. A deficiency of ascorbate required for these two hydroxylases results in scurvy, in which bleeding gums, swelling joints, and impaired wound healing result from the impaired stability of collagen. Biosynthesis of Nonessential Amino Acids Selenocysteine, the 21st Amino Acid: While the occurrence of selenocysteine in proteins is uncommon, at least 25 human selenoproteins are known. Selenocysteine is present at the active site of several human enzymes that catalyze redox reactions. Examples include thioredoxin reductase, glutathione peroxidase, and the deiodinase that converts thyroxine to triiodothyronine. Where present, selenocysteine participates in the catalytic mechanism of these enzymes. Biosynthesis of Nonessential Amino Acids Selenocysteine, the 21st Amino Acid: Significantly, the replacement of selenocysteine by cysteine can actually impair catalytic activity. Impairments in human selenoproteins have been implicated in tumorigenesis and atherosclerosis, and are associated with selenium deficiency cardiomyopathy (Keshan disease). Unlike hydroxyproline or hydroxylysine, selenocysteine arises cotranslationally during its incorporation into peptides. Biosynthesis of Nonessential Amino Acids Selenocysteine, the 21st Amino Acid: Biosynthesis of selenocysteine requires serine, selenite (SeO42−), ATP, a specific tRNA, and several enzymes. Serine provides the carbon skeleton of selenocysteine. Selenophosphate, formed from ATP and selenite (catalyzed by selenophosphate synthetase), serves as the selenium donor. Biosynthesis of Nonessential Amino Acids Selenocysteine, the 21st Amino Acid: The specific tRNASec is first charged with serine by the ligase that charges tRNASer. Subsequent replacement of the serine oxygen by selenium from selenophosphate. The formed selenocysteine can then be incorporated into proteins. Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids Biosynthesis of Nonessential Amino Acids