Amino Acid Metabolism (original) (raw)

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); CarboxypeptidaseA (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 aspartateto feed urea cycle.

Aminotransferase:�������������� a-amino acid + a-ketoglutarate � a-keto acid + glutamate

����������������������������������������� Glutamate + Oxaloacetate � Aspartate+ a-ketoglutarate

����������������������������������������� Cofactor:pyridoxal phosphate/pyridoxaminephosphate

����������������������������������������� 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:

Carbamoylphosphate 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)

Overall:

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 ketonebodies (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

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Metabolic defects in amino acid metabolism:

PKU = hyperphenylalaninemiacaused 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-aminolevulinicacid (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 hemesynthesis.� Erythropoietic or hepatic.

Degradation of Heme:� Occurs in liver and spleen.� Heme is converted to biliruben (requires NADPH).� Transported in blood via bilirubinalbumin 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 hepatocellularjaundice.

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.