Individual Amino Acid Metabolism 3 (Lecture) PDF

Biochemistry Metabolism of individual amino acids 3 (lecture) Medical Biochemistry & Molecular Biology  Objectives  To classify amino acids into essential or non essential / glucogenic  To identify biosynthesis and fate of each amino acid  To list f...

Biochemistry Metabolism of individual amino acids 3 (lecture) Medical Biochemistry & Molecular Biology  Objectives  To classify amino acids into essential or non essential / glucogenic  To identify biosynthesis and fate of each amino acid  To list function, metabolic role and important derivative of each amino acid of each amino acid  To describe metabolic inborn error or disorders. Metabolism of individual amino acids (3) By Dr/ Hend Nasr Assistant professor of medical biochemistry Metabolism of individual amino acids: The metabolism of each amino acid includes the following: 1. It is essential or non essential and if non essential how it is formed in the body. 2. Glucogenic or ketogenic. 3. Functions and important derivatives. 4. Metabolic inborn errors or disorders: these are genetic disorders in most cases due to gene mutations that result in enzyme deficiency. Metabolic fate of amino acid carbon skeletons: Amino acids can be classified into: 1- Ketogenic amino acids: they give acetyl-CoA or acetoacetyl-CoA which give ketone bodies e.g. leucine and lysine (theoretically mixed). 2- Both glucogenic and ketogenic (mixed): they can give both glucose and ketone bodies e.g. phenylalanine, tyrosine, tryptophan and isoleucine. 3- Glucogenic amino acid: they give glucose through intermediate in Kerbs’cycle e.g. the rest of amino acids. Alanine - Non essential amino acid formed from pyruvic acid by transamination. - Glucogenic amino acid being converted to pyruvic acid.  Alanine - Function: It is released from the muscles during starvation and changed to glucose in the liver by gluconeogensis to supply blood glucose by glucose alanine cycle. Serine: Non essential amino acid formed: 1. From glycine by serine hydroxymethyl transferase. Serine: 2- From glucose by glycolysis it forms 3-phosphoglycerate then it changed to serine as follows. Serine: Glucogenic: Serine by serine dehydratase gives glucose.  Serine: Functions and important derivatives: 1. It forms glycine by serine hydroxymethyl transferase, and also forms one carbon group (methyleneTHFA-CH2 THFA) which enter in C8 of purine ring. 2. It provides the carbon skeleton of cysteine. Serine + Homocysteine → Cystathionine → Cysteine + Homoserine. 3. Synthesis of ethanolamine and choline (phospholipids synthesis). Serine: Functions and important derivatives: 4. Serine is important in synthesis of sphingosine (conjugation of serine with palmityl-CoA) which forms sphingomylin and sphingolipids. 5. The carbohydrate radicals present in some types of glycoproteins and proteoglycans are connected to the hydroxyl group (e.g. serine).  Serine: Functions and important derivatives: 6. Serine plays an important role in regulation of enzyme activity by addition of phosphate to form phosphoserine in protein structure or by removal of phosphate from phosphoserine (covalent modification of enzyme activity). Many enzymes are regulated by this mechanism, key enzymes of glycolysis, glycogen synthase, glycogen phosphorylase and hormone sensitive lipase. Threonine: - Threonine is essential amino acid. - It is glucogenic amino acid: as by deamination it gives α-ketobutyrate which undergoes oxidative decarboxylation by α−ketobutyrate dehydrogenase complex forming propionyl CoA. PropionylCoA is glucogenic as by carboxylase it gives methyl malonyl CoA, which is changed to succinyl CoA. Threonine: Functions and important derivatives: 1- It gives Glycine by threonine aldolase. (Glycine gives serine and serine is glucogenic as it gives pyruvic acid). 2- OH of threonine can bind phosphate group of certain enzymes. Glycine - Structure: - Non essential amino acid as it is formed from: ✓ Serine by serine hydroxyl methyl transferase. ✓ From threonine by threonine aldolase. ✓ By glycine synthase (reversal of glycine cleavage). ✓ From glyoxalate by transamination. Glycine synthase ( reversal of glycine cleavage): NH3 From glyoxalate by transamination: Gylcine Glycine fate: Glycine is glucogenic amino acid as it forms serine by hydroxymethyl transferase and serine forms pyruvic acid by serine dehydratase. Functions and important derivatives: 1. Synthesis of amino acid serine by hydroxymethyl transferase. 2. Synthesis of creatine with arginine to form guanidoacetic acid, 3. Synthesis of heme as glycine condenses with succinyl CoA by ALA synthase enzyme to form delta amino levulinic acid (ALA).ALA synthase is the key enzyme for heme synthesis. 4. Synthesis of purine nucleotides: the whole molecule of glycine is incorporated into the purine ring (C4,C5 and N7,). 5. Synthesis of protein: glycine is the main amino acid in collagen structure (it forms 30% of collagen molecule). 6. Glutathione synthesis: Glutathione is tripeptide formed from glutamic acid, cysteine and glycine. Functions and important derivatives: 7- Synthesis of bile salts: glycine conjugates with bile acids to form bile salts e.g. glycocholic acid with sodium to form sodium glycocholate. 8- Detoxification of benzoic acid: benzoic acid is used in small amounts as preservative in foods. Glycine united with it to form hippuric acid. Functions and important derivatives: 9. Glycine by glycine cleavage system is converted to NH3 ,CO2 and methylene- tetrahydrofolate (CH2-FH4). 10. Glycine is deaminated by glycine oxidase to form glyoxylic acid which by oxidative decarboxylation is changed to formic acid which forms formyl- tetrahydrofolic acid. 11. Glycine act as neurotransmitter, it is present in brain stem & spinal cord. it opens chloride specific channels. In moderate levels, it is inhibitory & at high level it is stimulatory.  Metabolic inborn errors of glycine : 1- Primary hyperoxaluria: Congenital disease caused by decreased metabolism of glyoxalic acid either by: a. Oxidative decarboxylation to formic acid, or b. Transamination to glycine. - Glyoxalic acid is accumulated and is oxidized to oxalic acid. - There is excretion of large amount of oxalate in urine. - Oxalate reacts with calcium forming insoluble Ca, oxalate stone in urinary tract. - Large stones if bilateral may cause renal failure. Metabolic inborn errors of glycine : 2- Hyperglycinemia: There is increased in glycine level in blood, caused by deficiency of glycine cleavage system. 3- Glycinuria: There is increased excretion of glycine in urine, caused by congenital decreased renal tubular reabsorption of glycine.