Nitrogen Metabolism - Seidler Flashcards
Amino acid pool
Population of free AA in the body
N released during AA degradation is converted to urea and excreted in urine
Hartnup disease
Tryptophan - defect in transporter
Sxs - nystagmus, FTT, intermittent ataxia
Cystinuria
Dimeric AA cysteine, Arg, Lys
Cystine crystals = stones in kidneys = renal colic
Glucogenic AA
18 of 20 AA
Can be degraded to pyruvate or intermediates of the TCA cycle
Keto acid dehydrogenase enzyme complexes
Branched chain a-keto acid dehydrogenates
Requires 5 cofactors - TPP, lipoic acid, CoA, FAD, NAD
Unidirectional reaction - E1, E2, E3
Maple syrup urine disease
Presence of branched chain AA and there a-keto derivatives in urine
Also accumulates in blood - brain problems
What is something that can sometimes fix maple syrup urine disease?
Thiamine supplementation
What can lead to secondary PKU?
Defects in biosynthesis or regeneration of tetrahydrobiopterin (THB)
PKU
Defects in activity of phenylalanine hydroxyls activity
Disrupts NT and blocks AA transport in brain and myelin
Tyrosinemias
3 types
Type I most common
Characterized by elevated blood tyrosine
Alkaptonuria
Defect in homogentisate oxidase - an enzyme in Tyr degradative pathway
Causes it to accumulate
Blue diaper
MAO and COMT
2 enzymes involved in degradation of dopamine into homovallic acid (HVA)
Also VMA
Both HVA and VMA in urine of pts
What is the toxic agent in ammonia toxicity?
Uncharged ammonia - NH3
Due to its ability to cross the membrane = edema
Gout
High levels of uric acid in blood due to overproduction
Lesch-Nyhan syndrome
Tx - colchicine
Hyperammonemia
Results from defects in any of 6 enzymes associated with urea cycle or 3 transporters
Tx - limit protein intake
Type I citrullinemia
Autosomal recessive
Def in arginosuccinate synthetase
Type II citrullinemia
Less common in adults
Defect in transporter Citrin
Unconjugated bilirubin
Insoluble in water - Corbert’s?
Conjugated bilirubin
Soluble in water - found in urine
Cholestasis
5 Normal nitrogen excretory compounds
Urea Uric acid Ammonia Urobilinogen Creatinine
Trp derivatives
Niacin
Serotonin –> Melatonin
Tyr derivatives
Dopa
Dopamine
NE
Epinephrine
SAM
functions as a methyl donor for various reactions
ex. NE to Epi
Homocystinuria
Risk factor for atherosclerosis
Excess ammonia removed as either
GLU or GLN
Urobilin
Breakdown of urobilinogen
Gives urine yellow color
