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 Ala, Gly Ser); Carboxypeptidase A (amine side of Ala, Ile, Leu, Val); Carboxypeptidase B (amine side of Arg, lys)

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 a-keto acid + glutamate

Glutamate + Oxaloacetate Aspartate + a-ketoglutarate

Cofactor: pyridoxal phosphate/pyridoxamine phosphate

High serum AST and ALT indicate liver damage.


Oxidative Deamination: Glutamate dehydrogenase (mitochondria)

Glutamate + NAD+ (NADP+) a-ketoglutarate +NADH (NADPH) + NH3

Allosteric Regulators: ATP/GTP inhibit; ADP/GDP activate


Urea Cycle (liver):


Mitochondrial reactions:

Carbamoyl phosphate synthetase I:

CO2 + NH4 + 2 ATP carbamoyl phosphate (rate limiting)

Ornithine transcarbamoylase:

L-ornithine + carbamoyl phosphate L-citrulline + Pi


Cytosol reactions:

L-citrulline + L-Aspartate + ATP Argininosuccinate + AMP + PPi (argininosuccinate synthase)

Argininosuccinate Fumarate + L-Arginine (argininosuccinate lyase)

L-Arginine Urea + L-ornithine (arginase)



Aspartate + NH3 + CO2 + 3 ATP 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 a-keto acid + nonessential amino acid


Phenylalanine hydroxylase:

Phenylalanine + O2 + coenzyme tetrahydrobiopterin 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.


Glycine + succinyl CoA d-aminolevulinic acid (ALA) [d-aminolevulinic synthase]

Regulation by negative feedback (hemin)

Increased ALA synthase production via activation of P450s


d-aminolevulinic 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.