Amino Acid Metabolism
Digestion of Dietary Protein:
Stomach: HCl (denature) and Pepsin
Pancreas: Trypsin (carbonyl
of arg and lys);
Chymotrypsin (carbonyl of Trp,
Tyr, Phe, Met, Leu); Elastase (carbonyl of
Small Intestine: aminopeptidase (cleaves N-terminal residue of oligopeptides)
Nitrogen Removal from Amino Acids: make ammonia or aspartate to feed urea cycle.
Aminotransferase: a-amino acid + a-ketoglutarate à a-keto acid + glutamate
Glutamate + Oxaloacetate à Aspartate + a-ketoglutarate
Cofactor: pyridoxal phosphate/pyridoxamine phosphate
High serum AST and ALT indicate liver damage.
Oxidative Deamination: Glutamate dehydrogenase (mitochondria)
Glutamate + NAD+ (NADP+) à a-ketoglutarate +NADH (NADPH) + NH3
Allosteric Regulators: ATP/GTP inhibit; ADP/GDP activate
Urea Cycle (liver):
Carbamoyl phosphate synthetase I:
CO2 + NH4 + 2 ATP à carbamoyl phosphate (rate limiting)
L-ornithine + carbamoyl phosphate à L-citrulline + Pi
L-citrulline + L-Aspartate + ATP à Argininosuccinate + AMP + PPi (argininosuccinate synthase)
Argininosuccinate à Fumarate + L-Arginine (argininosuccinate lyase)
L-Arginine à Urea + L-ornithine (arginase)
Aspartate + NH3 + CO2 + 3 ATP à Urea + fumarate + 2 ADP + AMP + 2 Pi + PPi + 3 H2O
Urea is transported to kidneys for excretion
Metabolism of ammonia:
Sources: amino acids, glutamine (glutaminase), bacteria in intestine, from amines (catecholamine degradation), purine and pyrimidine catabolism
Transport of ammonia: urea and glutamine
Hyperammononemia: ammonia intoxication - tremors, slurring of speech, and blurring of vision, coma/death. Cause by cirrhosis of the liver or genetic deficiencies
Catabolism of Amino Acids
Ketogenic: formation of ketone bodies (leucine and lysine, exclusively)
Glucogenic: intermediates of citric acid cycle (see figure 22.3)
Essential vs. non-essential: PVT TIM HALL
Cofactors to remember: SAM, Biotin, Folic Acid (carriers of one-carbon units)
Biosynthesis of nonessential amino acids:
TCA cycle member + amino acid à a-keto acid + nonessential amino acid
Phenylalanine + O2 + coenzyme tetrahydrobiopterin à tyrosine + H2O + dihydrobiopterin
Metabolic defects in amino acid metabolism:
PKU = hyperphenylalaninemia caused by deficiency in phenylalanine hydroxylase or deficiency in coenzyme tetrahydrobiopterin. No tyrosine, no catecholamines
Conversion of Amino Acids to Specialized Products
Amino acids are precursors for porphyrins, neurotransmitters, hormones, purines, and pyrimidines
Porphyrins: biosynthesis of heme, important in coordinating iron.
succinyl CoA à
Regulation by negative feedback (hemin)
d-aminolevulinic à porphobilinogen (d-aminolevulinic acid dehydrase, inhibited by lead)
Porphyrias: defects in heme synthesis. Erythropoietic or hepatic.
Degradation of Heme: Occurs in liver and spleen. Heme is converted to biliruben (requires NADPH). Transported in blood via bilirubin albumin complex to liver where it is conjugated and then excreted with bile.
Jaundice: yellow skin and sclerae cause by deposition of bilirubin. Hemolytic, obstructive, or hepatocellular jaundice.
Creatine: derivative Creatine phosphophate can donate phosphate group to ADP to form ATP in muscles. Synthesized from arginine and glycine precursors. Used as indicator of Kidney function.
Histamine: Synthesized from Histadine, used as neurotransmitter. Powerful vasodilator.
Serotonin: Neurotransmitter synthesized from tryptophan.
Catecholamines: Synthesized from tyrosine.
Melanin: Also synthesized from tyrosine.