amino acid catabolism - western oregon university › ~guralnl › 451amino acid catabolism.pdfamino...
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Amino Acid Catabolism
• Dietary Proteins• Turnover of Protein• Cellular protein • Deamination• Urea cycle• Carbon skeletons of
amino acids
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Amino Acid Metabolism
•Metabolism of the 20 common amino acids is considered from the origins and fates of their:
(1) Nitrogen atoms (2) Carbon skeletons
•For mammals: Essential amino acids must be obtained from dietNonessential amino acids - can be synthesized
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Amino Acid Catabolism
• Amino acids from degraded proteins or from diet can be used for the biosynthesis of new proteins
• During starvation proteins are degraded to amino acids to support glucose formation
• First step is often removal of the α-amino group
• Carbon chains are altered for entry into central pathways of carbon metabolism
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Dietary Proteins
• Digested in intestine • by peptidases • transport of amino acids • active transport coupled with Na+
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Protein Turnover
• Proteins are continuously synthesized and degraded (turnover) (half-lives minutes to weeks)
• Lysosomal hydrolysis degrades some proteins
• Some proteins are targeted for degradation by a covalent attachment (through lysine residues) of ubiquitin (C terminus)
• Proteasome hydrolyzes ubiquitinated proteins
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Turnover of Protein • Cellular protein • Proteasome degrades
protein with Ub tags • T 1/2 determined by
amino terminus residue • stable: ala, pro, gly, met
greater than 20h • unstable: arg, lys, his,
phe 2-30 min
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Ubibiquitin
• Ubiquitin protein, 8.5 kD• highly conserved in yeast/humans • carboxy terminal attaches to ε-lysine amino group • Chains of 4 or more Ub molecules target protein for
destruction
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Degradation-- Proteasome
• Proteasome degrades protein with Ub tags • 26s: two subunits, 20s (catalytic) and 19s
(regulatory)• Releases peptides 7-9 units long
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Deamination
• Collect NH3 from tissues • alanine from muscle • glutamine from other tissues • glutamate from liver
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Transamination Reactions
• Transfer of an amino group from an α-aminoacid to an α-keto acid
• In amino acid biosynthesis, the amino group of glutamate is transferred to various α-keto acids generating α-amino acids
• In amino acid catabolism, transamination reactions generate glutamate or aspartate
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Transamination
• cytosol of liver • collect in glutamate • glutamate transferred to mitochondria
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Mechanism
• Pyridoxal phosphate co-factor
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Schiff base• Ping pong • Keto acid
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Serine & Threonine deamination
• Dehydratase reaction• Remove H2O first• Serine pyruvate• Threonine α-
ketobutyrate
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Oxidative deamination
• glutamate transferred to mitochondria • Glutamate dehydrogenase
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Urea cycle• In Liver• Glutamate dehydrogenase• CPS I • bicarbonate and ammonia react • In mitochondria: reactions • cytosolic reactions • arginase releases urea • remove waste products • tied to TCA cycle
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Urea cycle
• Mitochondria reactions
• Cytosolic reactions
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Mitochondrial Reactions
• CPS I • Bicarbonate and ammonia react• Orinithine transcarbamolyse• Citrulline transported to cytosol
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Cytosolic reactions
• Arginase releases urea • remove waste products: ammonia/bicarbonate• tied to TCA cycle
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Urea cycle and TCA cycle
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Glucogenic vs ketogenic amino acids
• Glucogenic amino acids can supply gluconeogenesis pathway via pyruvate or citric acid cycle intermediates
• Ketogenic amino acids can contribute to synthesis of fatty acids or ketone bodies
• Some amino acids are both glucogenic and ketogenic
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Carbon skeletons of amino acids
• glucogenic• ketogenic• Phenylalanine
example • Autosomal genetic
defect
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Phenylalanine Metabolic defect
• Genetic defect • Recessive• Hydroxylase defect• Minor pathway
produce Phenylpyruvic acid
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