Moving Nitrogen Around Flashcards
Describe Nitrogen Balance
Positive Nitrogen Balance: Excess nitrogen in the body Nitrogen intake > Nitrogen Excretion Negative Nitrogen Balance: Low Nitrogen in body Nitrogen intake < Nitrogen Excretion
Aminotransferases
(Transaminases)
transfer of an amino group of an amino acid to an a-keto acid
Important in the synthesis of amino acids, which form proteins. In medicine, they are an important indicator of liver damage (highest concentration of these in the liver).
Co-factor: Pyridoxal Phosphate
Glutamate dehydrogenase
Converts Glutamate to Alpha-KG and NH4+. NH4+ then enters the urea cycle. Can also be used in the reverse direction to synthesize glutamate.
Important Enzymes in Nitrogen Movement
Aminotransferases: transfer amine group from amino acid to Alpha-KG
Glutamine Synthetase: Puts amine/amide onto Glutamate to form Glutamine. (Puts the N passenger on the Glutamine bus, where it rides to the liver.)
glutaminase breaks down Glutamine in the liver to form glutamate and NH4+, which enters urea cycle
glutamate dehydrogenase Converts Glutamate to Alpha-KG and NH4+. NH4+ then enters the urea cycle. Can also be used in the reverse direction to synthesize glutamate.
Glutamine Synthetase
Glutamine Synthetase: Puts amine/amide onto Glutamate to form Glutamine. (Puts the N passenger on the Glutamine bus, where it rides to the liver.)
Glutaminase
glutaminase breaks down Glutamine in the liver to form glutamate and NH4+, which enters urea cycle
Discuss the diagnostic significance of aspartate aminotransferase and alanine aminotransferase
AST/ALT serve as markers of how damaged a liver is. When hepatocytes die, they release out these enzymes into the serum, so the higher the level of these enzymes, the more liver damage has occurred (they would be highest as a result of some sort of acute and significant damage to the liver: e.g. viral hepatitis or some sort of liver toxin)
Describe the significance of the urea cycle in removing nitrogen and the presentation of hyperammonemia with defects in urea cycle enzymes.
Ammonia is a toxic byproduct of protein catabolism and degradation. The human body handles this by converting ammonia to the the much less toxic compound urea. Ammonia is then secreted, as urea, through the urine.
The urea cycle is handled in the liver and is not a very reversible process. Thus, any deficiency in an enzyme involved in the urea cycle, as well as liver damage, will impair the body’s ability to excrete ammonia.
Patients will present with high levels of ammonia on blood test and CNS issues that gradually get worse until they go into a coma (e.g. lethargy, fatigue, loss of appetite, vomiting, seizures)
What structures result from de-amination reactions
Glutamate and an a-keto acid
Nitrogen Movement Systems: Big Picture
–Alanine or Cahill cycle: When muscles degrade amino acids for energy needs, alanine transports the resulting NH3 from muscle to the liver. Alanine is then broken down into pyruvate (which is used for gluconeogenesis in the liver and sent back into the blood as glucose) and NH4+, which goes into the Urea cycle for disposal.
– Glutamine synthase/glutaminase system: Most Nitrogen in the body is moved via Glutamine. When tissues other than muscles degrade amino acids, the resulting NH3 rides on glutamine to the liver. The ammonia is then cut out to regenerate glutamate and fed into the Urea cycle for disposal.
Ornithine transcarbamoylase (OTC) deficiency.
Most common urea cycle disorder. X-linked recessive.
A deficiency in OTC causes urea cycle deficiency. As an early enzyme in the urea cycle, OTC deficiency may cause a more severe hyperammonemia than other urea cycle enzyme deficiencies
Symptoms: tremor, slurred speech, vomiting, blurred vision) no megalablastic anemia
Ornithine transcabamylase
Urea cycle enzyme that catalyzes the reaction between ornithine and carbamoyl phosphate and thus allows a nitrogen to enter the Urea cycle.
Carbamoyl Phosphate Synthetase I
Catalyzes the key regulatory step in the Urea cycle
CO2 + NH3 –> Carbamoyl Phosphate (which then combines with Ornithine to enter the Urea cycle)
Deficiency would cause hyperammonemia in infants.
Urea Cycle
Amino Acids are broken down in the body to form Acetyl-CoA and pyruvate to be used as fuel. This liberates NH3, which is toxic to the body. Excess NH3 is converted to Urea via the Urea cycle in the liver and then excreted by the kidneys.
Disease associated with negative nitrogen balance
Marasmus: general starvation
Kwashiorker: protein starvation
- ascites, edema, fatigue, loss of muscle/teeth/hair
