Amino Acid Catabolism Lecture PDF

Catabolism of Amino acids Lecture all memorization Dr. Sarray Sameh, Ph.D Introduction Amino acid catabolism is part of the whole body catabolism Nitrogen enters the body in a variety of compounds; the most important being amino acids present in the dietary protein Nitrogen leaves the body as urea,...

Catabolism of Amino acids Lecture all memorization Dr. Sarray Sameh, Ph.D Introduction Amino acid catabolism is part of the whole body catabolism Nitrogen enters the body in a variety of compounds; the most important being amino acids present in the dietary protein Nitrogen leaves the body as urea, ammonia and other products derived from amino acid catabolism Amino acid degradation - The major site of amino acids degradation in mammals is the liver - The catabolism of amino acids involves : - Removal of amino groups - Urea cycle - Break down of the resulting carbon skeletons. - These products enter the pathway of intermediary metabolism resulting either : - Synthesis of glucose or lipids or - in the production of energy through their oxidation by the TCA cycle Amino acids can be classified as glycogenic and/or ketogenic based on which of the 7 intermediates are produced during their catabolism 7 intermediates: Glucogenic AA Ketogenic AA -pyruvate, - Their catabolism yields to - Their catabolism yields to acetyl CoA, pyruvate or one of the either Acetoacetate or one intermediates of TCA cycle of its precurssor: acetyl acetoacetate, CoA or acetoacetyl CoA (-Ketoglutarate, Succinylα-ketoglutarate, CoA, Fumarate, Oxaloacetate. succinyl CoA, - These intermediates are - Leucine and Lysine are the substrates for glucogenesis only exclusively ketogenic oxaloacetate (Give rise to the formation of amino acids found in fumarate. glucose in the liver, kidney protein. and glycogen in the muscle) I- Amino acids that forms oxaloacetate f If oxaloacetate Asparagine and Aspartate form oxaloacetate formed , it's IS glucogenic - Asparagine is hydrolysed by Asparaginase, releasing Ammonia and Aspartate. - Aspartate loses its amino group by transamination to form oxaloacetate. - Oxaloacetate is an intermediate of the TCA cycle; so, it can be incorporated in (Oxaloacetate condenses with acetyl CoA to form citrate in the first reaction of Krebs cycle). aspargine Aspartate ammonia aspartate & amino loses its to form oxaloacetate · by : transamination enzyme : asparaginase C · TCA oxaloacetate for oxaloacetate - = acetyl CoA citrate first reaction of Kreb II- Amino acids that forms -ketoglutarate Glutamine, Proline, Arginine, Histidine 1- Glutamine: Keto = gaph -GLutamine is hydrolysed to glutamate and ammonia by the enzyme glutaminase. glutamine glutamate ammoula enzyme used : Glutimase - Glutamate is converted to -ketoglutarate by transamination or through oxidative deamination by glutamate dehydrogenase 2- Proline: -Proline is oxidized to glutamate. - Glutamate is transaminated or oxidatively deaminated to form -ketoglutarate Proline oxidized J glutamate transaminated/ Oxidatively deaminated A a-Retoglutarate Arganine 3- Arginine arginase & or withine -Arginine is cleaved by arginase to produce ornithine. W a-Retoglutarate - Ornithine is subsequently converted to -ketoglutarate arginase Ornithine aminotransferase 4- Histidine - Is oxidatively deaminated by histidase to urocanic acid which subsequently forms N-formiminoglutamate (FIGlu). histadine A urocanic acid I N-formiminoglutamate - N-formiminoglutamate donates its formimino group to tetrahydrofolate leading to glutamate release which is then degraded to -ketoglutarate. & a-retoglutamate III-Amino acids that forms pyruvate Ala, Ser, Gly, Cys alanine serine glycine cystine 1- Glycine : Can either be: - converted to serine by addition of methylene group from N5,N10-methylene-tetrahydrofolate or - oxidized to CO2 and NH4+ 2- Serine: following the conversion to glycine catalyzed by serine hydroxyl methyltransferase, Serine can also be converted to pyruvate by serine dehydratase 3- Alanine: it loses its amino group by Transamination to form pyruvate by ALT 4- Cystine: - is reduced to cysteine by cystine reductase using NADH, H+ as a reductant. - Cysteine undergoes desulfuration to yield pyruvate IV- Amino acids that form fumarate Phenylalanine and Tyrosine they  Hydroxylation of phenylalanine leads to the formation of tyrosine.  This reaction is catalyzed by phenylalanine hydroxylase;  The metabolism of phenylalanine and tyrosine merge to the formation of fumarate and acetoacetate.  Inherited deficiencies in enzymes of phenylalanine and tyrosine metabolism lead to diseases: *Phenylketonuria: deficiency in phenylalanine hydroxylase; *Albinism tyrosin defiency no melanin are interlinked VIII- Catabolism of the branched chain amino acids The branched amino acids, isoleucine, leucine and valine are essential amino acids In contrast to the other amino acids, they are metabolized primarily by peripheral tissues (particularly muscle), rather than by the liver. Leucine (ketogenic): forming acetyl CoA and acetoacetate Valine (glucogenic); yields succinyl CoA Isoleucine (both ketogenic and glucogenic): yields acetyl CoA and succinyl CoA Because these 3 amino acids have similar route of catabolism, it is convenient to describe them as a group VII- other amino acids that form acetyl CoA or acetoacetyl CoA Lysine is exclusively ketogenic. Lysine is ultimately converted to acetoacetyl CoA. Tryptophan: is both glucogenic and ketogenic because its catabolism yields Alanine and acetoacetyl CoA Threonine: is both glucogenic and ketogenic and yields acetyl CoA and succinyl CoA Catabolism of Threonine: is both glucogenic and ketogenic. 2 ways: - Threonine aldolase cleaves threonine to acetaldheyde and glycine. - Oxidation of acetaldheyde to acetate is followed by formation of acetyl CoA OR - Dehydrated and converted to propionyl CoA precursor of succinyl CoA Metabolism of Methionine form SUCCInYI COA - is converted to S-adenosylmethionine (SAM), methyl group donor in one carbon metabolism. - A source of homocysteine a metabolite associate with vascular diseases (MI, stroke, pulmonary embolus…) Formation of SAM: transfer of adenosyl group from ATP to sulfur atom of methionine: Transfer of the methyl group attached to SAM by methyltransferases to a variety of acceptor molecule (synthesis of choline…). We obtain S-adenosylhomocysteine (SAH) C- SAH is hydrolysed to homocysteine and adenosine. - Homocysteine has two fates: a) In case of Methionine deficiency, homocysteine, is remethylated and form methionine. b) If Methionine stores are adequate, homocysteine will be degraded into cysteine. Homocysteine degradation: Homocysteine condenses with serine to form cystathionine (require PLP (vitamin B6)) and catalyzed by cystathionine synthetase; Absence of this enzyme leads to homocystinuria (buildup of homocysteine in your blood which can cause severe complications) homocystelne + serine = cystathionine END!