Nitrogen Metabolism Flashcards
How do we get Nitrogen? (3)
Dietary
Body Protein
Synthesis of nonessential AA
Nitrogen source
Glutamate in liver
Glutamine outside liver
First step of nitrogen removal? via what enzyme?
Oxidative deamination
Glutamate Dehydrogenase
Types of kidney stones
1) Calcium Oxalate Crystals
- most common
- suboptimal diet, hyperthyroidism
2) Uric Acid Crystals
- gout
3) Struvite Crystals
- ca/phosphate imbalance
- alkaline environment
4) Cystine Crystals
- purely genetics
Rate Limiting Step of Urea Cycle
Carbamoyl Phosphate synthetase I
Normal Flow of Filtrate
Re-absorption of AA and glucose in PCT
After PCT-> transport protein from SLC (solute carrier) gene mediate reuptake
Hartnup Disease
- defective transport of neutral (nonpolar) AA’s
Ala, Val, Leu, Ile, Phe, Trp
Tryptophan
-precurose to serotonin, melatonin, and niacin (will have deficiency)
autosomal recessive
- dermatosis
- triggered by light , strss
Treatment: increase niacin, high protein diet
daily nicotinamide to increase NAD -> more niacin
Cystinuria
autosomal recessive disorder
- defective amino acid transporter for cystine, ornithine, arginine, lysine (COAL)
- cystine crystal in positive notroprusside test
- renal colic, abdominal pain, hematuria
Two Variants
- homozygotes for both types=> high urinary excretion of COAL
1) Type I heterozygotes=> normal urinary AA excretion
2) Non type 1 heterozygotes => increased urinary excretion
Phenylketoruia
Defect in phenylalanine hydroxylase
- cannot convert Phe to Tyr
- musty odor in urine
- severe brain impairment
- block amino acid transport
- test positive for post-paturition Guthrie test ( at two weeks of age)
Treatment: tetrahydrobiopterin, limit diet Phe,
Tetrahydrobiopterin / dihydrobiopterin
TBH- cofactor in hydroxylation for Arg, Phe, Tyr, Trp
essential for NO production
defect in biosynthesis or regeneration of THB can lead to secondary PKU
-neurological dysfunction
Treatment: synthetic THB
Tyrosinemias
-Elevated Tyr in blood
Type 1- most severe
- excrete succinylacetone (toxic) -> renal tubule dysfunction and inhibit heme biosynthesis
- liver failure ->require liver transplant
Type 2- defective tyrosine aminotransferase
-lesions on skin and photophobia
Type 3- defective hydroxyphenylpyruvate oxidase
- intermittent ataxia
Alkaptonuria
-defective homogentisate oxidase (for Tyr degration)
autosomal recessive
black urine, IVD
Ammonia Toxicity
-excessive ammonia bc of urea cycle disorder/liver failure
- NH3 can easily permeate compared to NH4
- astrocyte swelling-> cerebral edema and intracranial hypertension
- disruption of GABA NT
- mitochondrial dysfunction
Gout
- high level of uric acid in blood (either overproduction or underexcretion)
- painful deposits of sodium urate in extremities
- caused by diet rich in purine (beans, spinach, lentils), alcohol, meat, seafood
- decrease GFR, tubular secretion, enhanced tubular reabsorption
Treatment: colchicine, allopurinol (inhibit xanthine oxidase)
Hyperammonemia
-defects in any six enzymes that are in urea cycle or 3 transporter
Transporters
- mitochondrial ornithine carrier
- mitochondrial Asp/Glu carrier
- dibasic amino acid transporter
- mitochondrial transporters defect more sever
-defect in ornithine transcarbamoylase (X-LInked) -> hyperammonemia, decreased BUN, orotic aciduria
Other enzymes=> hyperammonemia, citrullinemia, arginonosuccinate aciduria,
Treatment: limiting protein consumption or agents that promote secretion
