Metabolism of Amino Acid

Amino Acid Pool 1. Dietary protein The amount of free amino acids distributed throughout the body is called amino acid pool Plasma level for most amino acids varies widely throughout the day . It ranges between 4-8 mg/ dl It tends to increase in the fed state and tends to decrease in the post absorptive state Sources of Amino acid pool 1. Dietary protein 2. Breakdown of tissue protein 3. Biosynthesis of nonessential amino acids

Fate of Amino acid pool Biosynthesis of structural proteins. eg - tissue protiens Biosynthesis of functional proteins. eg- haemoglobin, myoglobin etc. Biosynthesis of small peptides of biological importance. eg- glutathione, endorphins 4. Biosynthesis of non protein nitrogens (NPN) as urea, uric acid, creatine , creatinine and ammonia 5. Catabolism of amino acids to give ammonia and α-keto acids

OVERVIEW OF AMINO ACID METABOLISM ENVIRONMENT ORGANISM Ingested protein Bio- synthesis Protein AMINO ACIDS Nitrogen Carbon skeletons Urea Degradation (required) 1 2 3 a b Purines Pyrimidines Porphyrins c Used for energy pyruvate α-ketoglutarate succinyl-CoA fumarate oxaloacetate acetoacetate acetyl CoA (glucogenic) (ketogenic)

Energy production from Amino Acids GLUCOGENIC AMINO ACIDS – Carbon skeleton can be converted to glucose TCA cycle intermediates or pyruvate (gluconeogensis) KETOGENIC AMINO ACIDS - Carbon skeleton can be converted to ketone bodies

GLUCOGENIC / KETOGENIC AMINO ACIDS

Urea Cycle Most animals convert excess nitrogen to urea, prior to excreting it. Urea is less toxic than ammonia. The Urea Cycle occurs mainly in liver. The 2 nitrogen atoms of urea enter the Urea Cycle as NH3 (produced mainly via Glutamate Dehydrogenase) and as the amino N of aspartate. The NH3 and HCO3- (carbonyl C) that will be part of urea are incorporated first into carbamoyl phosphate.

Function: detoxification of ammonia (prevents hyperammonemia) UREA CYCLE mitochondria cytosol Function: detoxification of ammonia (prevents hyperammonemia)

Catabolic pathways of Amino acids Transamination Deamination Transamidination Transamidation Decarboxylation

Transamination Transamination means transfer of amino group from α-amino acid and a new α-keto acid with formation of a new α-amino acid and a new α-keto acid . Liver is the main site of transamination All amino acids can be transaminated except lysine , threonine, proline and hydroxyproline. All transamination reactions are reversible It is catalyzed by aminotransfereses. It needs pyridoxal phosphate as a coenzyme.

Transamination Examples of transaminase Alanine transaminase Aspartate transaminase Glutamate transaminase

Deamination Deamination means the removal of amino group from α- amino acid in the form of amonia with the formation of α- keto acid The liver and kidney are the main sites for deamination Deamination may be oxidative or non-oxidative

Oxidative deamination Glutamate Dehydrogenase catalyzes a major reaction that effects net removal of N from the amino acid pool. It is one of the few enzymes that can use NAD+ or NADP+ as e- acceptor.

Some other pathways for deamination of amino acids: 1. Serine Dehydratase catalyzes: serine  pyruvate + NH4+ 2. Peroxisomal L- and D-amino acid oxidases catalyze: amino acid + FAD + H2O  a-keto acid + NH4+ + FADH2 FADH2 + O2  FAD + H2O2 Catalase catalyzes: 2 H2O2  2 H2O + O2