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Protein Catabolism ?Can you give me some examples of what chemicals you think youve used, or how you think chemistry may have impacted your life?
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Overview of Protein Catabolism
C/B 75-80% reused 30-40 g/day lost (5-7 g N assuming 16% N) Proteases are zymogens Excess amino acids are not stored Normal protein turnover 1-2% of body protein per day ~75-80% amino acids reused; lose g/day Not excreted as amino acids or ammonia
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Methods of Nitrogen Excretion
Uricotelic (birds, reptiles) Ammonotelic (fish) Ureotelic (mammals)
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Two Amino Acids are Used to Transport Nitrogen
Transaminase Nonspecific for one pair, specific for the other pair Pyr-Ala aKG-Glu are the two most common Gln synthetase particularly important to the brain
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Transamination Mechanism
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Urea Cycle Importance means of excreting nitrogen in nontoxic form
Location Mitochondrial matrix and cytoplasm of liver and kidney Reactions Energetics Regulation
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Intracellular Ammonium Generation
Glutaminase mitochondria only Liver quantitatively more important Oxidative deamination of Glu Only Glu DH can use NAD or NADP
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Carbamoyl Phosphate Synthetase I
Liver Mitochondrial enzyme RDS of urea cycle Activated by (requires) NAcGlu
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Ornithine Transcarbamoylase
Mitochondrial enzyme Transported to Cp after synthesis
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Arginosuccinate Synthetase
Cytoplasmic enzyme
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Arginosuccinase Enzyme restricted to liver and kidney
Fumarate converted back to Asp
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Arginase Primarily liver enzyme
Ornithine transported back into mitochondrion by ornithine-citrulline antiporter
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Regulation GluNAc as described earlier occurs by changing ATP affinity
10-20–fold change in enzyme levels based on “nitrogen balance” i.e. how much protein is consumed relative to needs
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Energetics False Claim #27 of Vegetarians
“consuming protein uses energy” 4 ATP equivalents consumed in the urea cycle However, the carbon backbone is now available for energy use Carnivores obtain large amount of energy from amino acid carbon, herbivores ~10-15%
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Carbon Backbone Catabolism
Glucogenic amino acids vs. ketogenic amino acids Glucogenic are converted to metabolite of glycolysis (e.g., pyruvate) and can be converted into glucose Ketogenic form molecules such as acetoacetate, which can be converted to fat Most amino acids are glucogenic and ketogenic Leu is the sole amino acid which is ketogenic
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Ala
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Gln, Glu
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Asn, Asp
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Thr, Ser, Gly
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Pro
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Met
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Arg
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Phe
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Phenylketonuria (PKU) is a Congenital Absence of Phe Hydroxylase
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Leu
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Maple Syrup Urine Disease
The result of branched chain amino acid dehydrogenase deficiency Oxidation products of keto compounds accumulate
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Histidine
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Cysteine Has Two Catabolic Pathways
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