Nitrogen Metabolism Flashcards
(32 cards)
What is the major source of nitrogen?
protein
What are the major nitrogen excretory compounds?
- Urea
- Ammonia
- Creatinine
- Uric acid
- Urobilinogen
What is nitrogen shuffling?
- AA’s convert to glutamate via transamination (needs PLP)
- Glutamine is main metabolic byproduct in extrahepatic tissues and this is the most prevalent nitrogen carrier in the blood
- Final ammonia sequestration is done by glutamate
- CPSase uses free ammonium to form carbamoyl phosphate feeding into urea cycle
A patient comes in and tells you their PMH. It is significant for a deficient membrane transporter in the gut. How would you expect their kidney function to be?
- The transporter proteins in the gut are the same found in the PCT, so active reabsorption will be decreased
Where will reabsorption of AA and glucose occur?
PCT
What disease has defective transport of neutral amino acids particularly trp?
Hartnup disease
What disease has defective transport of dibasic amino acids? What are these amino acids?
- Cystinuria
- Cystine
- Ornithine
- Arginine
- Lysine
After spending all weekend in the sun fishing, in an attempt to relieve the stress of medical school, a 26 yo male presents to urgent care with cutaneous hyperpigmentation. They also appear to have a tremor and minor cerebellar ataxia. What type of diet and supplementation would you recommend?
- Tx is directed towards replacing niacin
- High protein diet
- Nicotinamide supplementation
-
This is Hartnup disease, an AR disorder which results in defective aa transport of neutral AA’s particularly Trp.
- Trp is a precursor for NAD
What is the only way to diagnose Hartnup disease?
Chromatographic analysis of urine samples
A mother brings her 4th month old into the pediatrician for the first time. She had a smooth at home birth and neither her or her daughter have seen a doctor. She tells the doctor that her baby doesn’t show interest in much, isn’t reaching for anything, and has slow reflexes in general. She also states that her diapers have an odd musty smell to them. What enzyme is deficient, what causes the musty smell in the urine, and how would you suggest treating this?
- Phe Hydroxylase (PAH)
- Phe gets converted to phenylpyruvate and then to phenyllacetate which causes the musty smell
- Tx would be to limit dietary Phe, supply protein with synthetic formula supplemented with Tyr
- This is PKU
Defects in dihydrobiopterin reductase can lead to ___.
Defects in dihydrobiopterin reductase can lead to secondary PKU
What is tyrosinemia?
- Elevated blood levels of tyrosine
- Tx is restricted Phe and Tyr diet
How do you distinguish PKU from tyrosinemia?
Hypertyrosinemia
Tyrosinemia type I?
- Defect in fumarylacetoacetate hydrolase
- Infants have cabage like smell and develop severe liver failure w/o tx
- Most common type used to require liver transplant, now Nitisinone is the tx
Tyrosinemia type II?
- Defective tyrosine aminotransferase
- Palmar and plantar hyperkeratosis, corneal lesions and intellectual disablity
- AR and rare
Tyrosinemia type III?
- defective 4-HPPD
- results in various neuro deficiets
- Very very rare
- Confirmed by elevated 4-HPPD and hypertyrosinemia
What is Alkaptonuria?
- AR defective homogentistate oxidase which is part of the Tyr degradation pathway
- Black urine Black bone disease
- causes homogentisic acid to accumulate
- Homogentisic aciduria, ochronosis, arthritis
Distinguish Primary vs secondary hyperuricemia.
- Primary is the overproduction of uric acid
- Secondary is underexcretion of uric acid
For gout, Allopurinol is used as a tx. What does this inhibit?
Xanthine oxidase
How does ammonia toxicity result in a disruption of ATP production?
- There is a depletion of alpha ketoglutarate which is a major player in the TCA cycle
- A-KG gets converted back into glutamate
What does ammonia toxicity do to the body?
- excessive ammonia due to urea cycle disorders or liver failure, highly toxic for brain and CNS
- causes a pH imbalance, swelling of astrocytes leading to cerebral edema and intracranial htn
- TCA is disrupted
- Postsynaptic excitatory proteins are inhibited depressing the CNS
- Depletion of glutamate disrupts formation of GABA
- Mitochondria dysfxn also
What amino acid acts nitrogen flow regulator throughout the body, both accepting and donating nitrogen for eventual incorporation into the urea cycle? (Dr. Kinde)
- Glutamate
- Glutamate is the body’s nitrogen flow regulator. All transaminase reactions donate nitrogen from an amino acid substrate to a-ketoglutarate to form glutamate. Glutamate dehydrogenase is the key enzyme that will eventually oxidatively deaminate glutamate to form ammonia for incorporation into the urea cycle. (Dr. Kinde)
Defect in ornithine and citrate transporters, seen in the urea cycle, will result in ____.
Defect in ornithine and citrate transporters, seen in the urea cycle, will result in severe hyperammonemia
Deficiency in OTC?
- Build up of carbamyl phosphate in the mitochondria
- It spills into the cytosol
- Gets taken into the pyrimidine synthesis pathway
- Orotic aciduria occurs along with hyperammonemia
