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Amino Acid Oxidation and the Production of Urea
Amino acids
(1) derived largely from protein in the diet
(2) degradation of intracellular proteins
- significant contribution to the metabolic
energy
• Carnivores
• Herbivores
Amino Acid Oxidation and the Production of Urea
Metabolic Fates of Amino Groups
2. Nitrogen Excretion and the Urea Cycle
3. Pathways of Amino Acid Degradation
Dietary Protein Is Enzymatically Degraded to Amino Acids
1. Entry of protein into stomach
-> gastric mucosa to secret gastrin hormone
-> gastric hydrochloride – 1. antiseptic 2. denature globular protein
->pepsinogen – active pepsin in gastric juice
• Pepsin – hydrolyze the amino-terminal Tyr, Phe, Trp
• Secretin - stimulate pancrease to secret bicarbonate, neutralize the gastric HCl
• Cholectstokinin – stimulate secretion of pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase)
• Trypsin – carbonyl group of Lys, Arg
• Chymotrypsin - carbonyl group Tyr, Phe, Trp
• Carboxypeptidase – remove successive carboxyl- terminal residue
• Aminopeptidase - remove successive amino-terminal residue
Glutamate Dehydrogenase
• Complex allosteric enzymes
- six identical subunits
- positive modulator ADP,
negative modulator GTP (product of succinylCo-A
synthase reaction)
• Hepatocyte need fuels for citric acid cycle
- glutamate dehydrogenase activity is increased -> α-ketoglutarate available for the citric acid cycle -> releasing NH4+ for excretion
- glucose synthesis
• GTP accumulates in the mitochondria
-> oxidative deamination of glutamate is inhibited
Regulatory Pattern of Glutamate Dehydrogenase
Mutation – alters the allosteric binding site for GTP
Permanent activation of glutamate dehydrogenase
-> hyper-insulinism-hyperammonemia syndrome
->Characterized by elevated levels of ammonia in the bloodstream and hypoglycemia
Glutamine Transports Amonia in the Bloodstream
Ammonia Is toxic to Animals
NH4+ -> NH3 (base) + H+
Glutamate dehydrogenase reaction toward glutamate production ->limit the availability of α-ketoglutarate for the citric acid cycle
Toxic concentrations of NH4+ interfere with the very high level of ATP production
Depletion of neurotransmitter (glutamate and GABA) - brain
Nitrogen Excretion and the Urea Cycle
Urea Is produced from Amonia in Five Enzymatic Steps
Carbamoyl phosphate synthetase I
Ornithine transcarbamoylase
Argininosuccinate synthetase
Argininosuccinate lyase
Arginase
Amino Acid Oxidation and the Production of Urea
Metabolic Fates of Amino Groups
2. Nitrogen Excretion and the Urea Cycle
3. Pathways of Amino Acid Degradation
The Activity of the Urea Cycle Is Regulated at Two Levels
Genetic Defects in the Urea Cycle Can Be Life-Threatening
Essential
Amino acids
Amino Acid Oxidation and the Production of Urea
Metabolic Fates of Amino Groups
2. Nitrogen Excretion and the Urea Cycle
3. Pathways of Amino Acid Degradation
Pathways of Amino Acid Degradation
• 10 to 15% of the human energy production
Converge to form only 5 products
Enter citric acid cycle
The carbon skeleton – gluconeogenesis or ketogenesis or completely oxidized to CO2 and H2O
Several Enzymes Cofactor Play Important Roles in Amino Acid Catabolism
One carbon Transfer
Biotin
Tetrahydrofolate,
S-adenosylmethionine
Ten Amino Acids Are Degraded to Acetyl-CoA
alanine, glycine, serine, cysteine, tryptophan, and threonine.
2. tryptophan, lysine, phentlalanine, tyrosine, leucine and isoleucine
Five Amino Acids Are Converted to α-Ketoglutarate
Branched-Chain Amino Acids Are Not Degraded in the Liver
Branched side chains (leucine, isoleucine, valine) – oxidized in muscle, adipose, kidney and brain tissue
Branched-chain α-keto acids dehydrogenase complex
Maple syrup urine disease