BSC Hepatic Function Flashcards
how is ammonia transported in blood?
as glutamine. It is then transported to liver where it is reversed by enzyme glutaminase. The ammonia that is generated is detoxified into urea for excretion in the liver.
Production of Ammonia NH3
AA’s combine with alpha ketoglutarate to form glutamate. Glutamate is transported to liver as glutamine and goes to form NH4+ which enters the urea cycle and is excreted via urea.
carbamoyl phasphate synthetase I deficiency
deficiency leads to high ammonia in blood due to inability to excrete nitrogen:
- this enzyme binds ornithine to cirtrulline, and citrulline leaves the mitochondria
- urea is formed in cytosol of the liver
The urea cycle consists of five steps!!!
- Carbamoyl phosphate combined with ornithine to form citrulline (ornithine transcarbamoylase) in matrix, passes into the cytosol.
2 Citrulline is converted to arginino- succinate (argininsuccinate synthetase)
3 Argininosuccinate is cleaved (argininosuccinase) to yield fumarate & arginine which enters the citric acid cycle.
4 Formation of urea: arginine is converted to urea & ornithine (arginase)
Ornithine – product of the last reaction & substrate of first reaction (same as oxaloacetate in TCA)
- Formation of Urea
Five important enzymes or urea!!!
- carbamylphosphate synthetase I (CPSI),
- ornithine transcarbamylase (OTC),
- argininosuccinate sythetase (ASS),
- arginosuccinate lyase (ASL), and
- arginase.
A defect at any of the steps in the urea cycle can lead to accumulation of intermediate substrates,which in turn can have a range of effects on the body.
ornithine transcarbamoylase deficiency (OTC)
- X linked dominant - worse in males
- baby born with impaired urea formation due to defect in OT for urea cycle
- urine glutamine excretion is increased because it is excreted in compensation for inoperative urea cycle.
- free ammonia is toxic to brain, thus must be bound to glutamine.
- treatment: give less protein in the diet, so as to form less ammonia in the blood
Hartnup disease
In Hartnup disease (a defect in the transport mechanism of neutral amino acids), patients do not become deficient in these amino acids due to the activity of: PepT1
know insulin, glucagon, DM I, DM II
don’t need to know somatostatin, or anything that is happening inside the cell
DMII - receptors can be resistant to insulin, sometimes see high level of insulin, but does not alleviate the needs. Glucagon level is low.
don’t need glycolysis, glycogenolysis
Hunger DSA
know the 3-4 hormones: neuropeptide Y, Leptin, ghrelin, cortisol (know what happens when you are full, and what should be expressed). know what happens when you are obese.
Carbamoyl Phsophate Synthase I
- pacemaker enzyme of urea cycle
- it is needed to combine with ornithine to form citrulline
- during starvation, the activity of urea cycle is increased to meet protein catabolism - the major regulatory step is catalyzed by CPS-I
- Liver cirrhosis caused by alcoholism can interfere with this enzyme and cause hyperammonemia
CPS-1 deficiency
Carbamoyl Phosphate synthetase (CPS-1) deficiency. Along with OTC deficiency, deficiency of CPS1 is the most severe of urea cycle disorders. Individuals with complete CPS1 deficiency rapidly develop hyerammonemia in the newborn period. Children who are successfully rescued from crisis are chronically at risk for repeated bouts of hyperammonemia.
Citrullinemia type I deficiency
. Affected individuals are able to incorporate some waste nitrogen into urea cycle intermediates, which makes treatment easier
Argininosuccinic aciduria deficiency
This disorder also presents with rapid onset hyperammonemia in the newborn period.
This enzyme defect is past the point in the metabolic pathway at which all the waste nitrogen
has been incorporated into the cycle. Treatments requires only supplement of arginine.
Normal BUN levels
6-20 mg
