13 - NITROGEN METABOLISM

300 to 400 g/day

Rate of protein turnover in grams per day

Ammonotelic

Method of excretion of excess nitrogen in teleostean fish, which excrete toxic ammonia

Uricotelic

Method of excretion of excess nitrogen in birds, which excrete uric acid as guano

Ureotelic

Method of excretion of excess nitrogen land animals, which excrete water-soluble urea

Pyridoxal phosphate (B6)

Co-enzyme required in transamination reactions

Glutamate dehydrogenase

Enzyme that catalyzes oxidative deamination of glutamate in the liver & kidney to release ammonia

Glutamine

Major amino acid that transports ammonia from extrahepatic tissues to liver

Alanine

Cahill Cycle or

Glucose-Alanine Cycle

Primary amino acid utilized by muscles to transport ammonia to the liver

Liver

Organ where the urea cycle occurs exclusively

Carbamoyl phosphate synthetase I

NH3 + CO2→

Carbamoyl phosphate

Rate-limiting enzyme of urea cycle

N-acetylglutamate

Amino acid derivative that functions solely as an enzyme activator of urea synthesis

Ornithine transcarbamylase deficiency

Most common hereditary hyperammonemia; Only X-linked hyperammonemia

Carbamoyl phosphate synthetase-I deficiency

Most severe hereditary hyperammonemia

Hyperornithinemia, Hyperammonemia, Homocitrullinemia

(HHH) Syndrome

Disease caused by impaired transport of ornithine across the inner mitochondrial membrane

Lysine (K)

Leucine (L)

Purely ketogenic amino acids (2)

Phenylalanine (F)

Tyrosine (Y)

Isoleucine (I)

Tryptophan (W)

Threonine (T)*

*Some books consider threonine

Both glucogenic and ketogenic amino acids (5)

Tyrosine (Y)

Precursor amino acid to catecholamines, melanin, and thyroid hormones

S-adenosylmethionine

Substance synthesized from methionine and ATP that supplies methyl groups

Phenylalanine hydroxylase

May also be due to deficiency of tetrahydrobiopterin (co-factor)

Deficient enzyme in phenylketonuria

Alkaptonuria

Disease caused by deficiency of homogentisate oxidase presenting with black urine upon standing & ochronosis

Tyrosinase

May also be due to defective tyrosine transporters

Deficient enzyme in albinism leading to defective melanin synthesis

Cystathione β-synthase

Most common deficiency in homocystinuria, leading to ectopia lentis and propensity for stroke

Downward and inward

Outward & upward in

Marfan syndrome

Direction of ectopia lentis in homocystinuria

Cystine

Ornithine

Lysine

Arginine

Amino acids whose transport in the PCT is affected in cystinuria (4)

Methylmalonyl CoA mutase

Enzyme deficient in methylmalonic acidemia, important in the metabolism of some amino acids and odd-chain FA

⍺-ketoacid dehydrogenase complex

Enzyme deficient in maple syrup urine disease involved in the catabolism of branched chain amino acids

Histidase

Enzyme deficient in histidinemia, preventing conversion of histidine to urocanate

ALA synthase

Rate-limiting enzyme of heme synthesis

Lead (Pb)

Heme synthesis enzymes ALA dehydratase & ferrochelatase are inactivated by which heavy metal

Porphyria cutanea tarda

caused by uroporphyrinogen decarboxylase deficiency

Most common porphyria in adults

Porphobilinogen

δ-ALA

Intermediates that accumulates in acute intermittent porphyria

Erythropoietic protoporphyria

Ferrochelatase deficiency

Most common porphyria in children

ALAD porphyria

Acute intermittent porphyria

Porphyrias with NO cutaneous involvement

Crigler-Najjar Type I

Bilirubin glucuronyltransferase deficiency

Most lethal form of hereditary hyperbilirubinemia

Dubin-Johnson Syndrome

Hereditary conjugated hyperbilirubinemia characterized by grossly black liver with lysosomal pigment on histology