Nitrogen Metabolism Flashcards
The first step in nitrogen metabolism is:
Via which enzyme:
Oxidative deamination via glutamate dehydrogenase
Urea cycle
Asp + citrulline –> arginosuccinate –> fumarate (goes to TCA) + Arg –> urea and ornithine (+carbamoyl phosphate) –> citrulline
What is the carbon skeleton source for urea cycle reactions?
Aspartate
What cannot be resorbed in Hartnup’s?
In cystinuria?
Nonpolar AAs
Dibasic AAs
Why is Hartnup’s and Cystinuria a “double whammy” in a sense?
There is poor absorption in both the intestines and malabsorption.
Where does reabsorption of AA and Glc occur?
In the PCT
What gene/protein function in reuptake of Glc and AA?
SLC
Hartnup’s Disease has poor absorption which AAs?
Nonpolar
Ala, Ser, Thr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn and His
How does HD manifest? (5)
Infancy to thrive as an infant Nystagmus Ataxia Photosensitivity Pellegra
What is the treatment for HD generally? (3)
Niacin w/ a high protein diet and nicotinamide supplementation.
Trp pathway
Trp –> niacin –> NAD+/NADP+
Trp –> 5-hydroxytrptophan –> serotonin –> melatonin
How does niacin help in HD?
The de novo pathway does not work due to malabsorption of Trp.
Therefore, Niacin can convert to NAD+/NADP+
What are “dibasic” AAs? (4)
COAL Cys Orn Arg Lys
What doe patients present with in cystinuria? (2)
Renal crystals
Renal colic
Draw the Phe to Fumarate pathway
Phe –> Tyr –> p-Hydroxyphenylpyruvate –> homogentisate –> Maleylacetoacetate –> Fumarylacetoacetate –> Fumarate
Type II tyrosinemia occurs from:
Enzyme
From Tyr –> p-Hydroxyphenylpyruvate
tyrosine aminotransferase
Type III tyrosinemia occurs from:
Enzyme
p-Hydroxyphenylpyruvate –> Homogentisate
p-hydroxypyruvate oxidase
Alkaptonuria occurs from:
Enzyme
Homogentisate –> Maleylacetoacetate
homogentisate oxidase
Type I tyrosinemia occurs from:
Enzyme
Fumarylacetoacetate –> fumarate
fumarylacetoacetate hydrolase
PKU is a defect in which enzyme?
PAH
Phenylalanine hydroxylase
Instead of being metabolized normally to Tyr, what happens to Phe in PKU?
Phe –> phenylpyruvate –> phenylacetate
PKU disrupts what physiologically?
Neurotransmission and blocks AA transport in the brain.
Secondary PKU results from:
BH4 deficiency (a cofactor of PAH).
What test tests for PKU?
Guthrie test
PKU must be found when?
What levels of blood Phe are concerning?
Treatment of PKU
Before 2 wks
>360 umol/L
BH4
Tyrosinemia
Increased Tyr in the blood.
Which tyrosinemia is most common and what is teh treatment?
Type I
Liver transplant
Alkaptonuria
AKA black urine disease
Caused by accumulation of homogentisate
Noted also by black pigmentation in the IV disks
Auto recessive
Which AA must be supplemented in a patient with PKU?
Tyr
Ammonia toxicity
Excessive NH3
Causes pH imbalance, swelling in the brain
Ammonia can cause a depletion of what?
Glutamate, an NT in the brain
Gout
Build up of uric acid in the joints due to diets rich in purnies.
Treatment of gout
Colchicine, which decreases movement of granulocytes to the affected area.
Allopurinol, which inhibits xanthine oxidase
Altered uric acid excretion can come from (3):
Poor glomerular filtration, decreased tubular secretion or enhanced tubular resorption.
Purine rich foods (6):
Beans, spinach, lentils, alcohol, meat and seafood.
Hyperammonemia
Occurs in defects in any of the 6 enzymes in the urea cycle or with 3 transporters.
Carbamoyl phosphate synthetase II function
First step in de novo synthesis of pyrimidines
CPSaseI isoform chart (3)
Urea cycle
Mitochondrial
NAG-activated
CPSaseII isoform chart (3)
Pyrimidine synthesis
Cytosolic
PRPP-activated
Conjugated (direct) vs. unconjugated (indirect) bilirubin
Conjugated is soluble
Unconjugated is not soluble
Jaundice in newborns is due to:
Build up of unconjugated bilirubin as the baby’s liver is not matured enough to process.
Should return to normal 7-10 days after delivery
Physiological jaundice
Jaundice due to adult pathology - sickle cell, liver diseae, anemias, etc.
