Urea Cycle (Jenney) Flashcards
What are 2 pathways that result in glutamate?
NH4+ + alpha-ketoglutamate (glutamate dehydrogenase)
Glutamine + alpha-ketoglutarate (glutamate synthase)
What molecule is a nitrogen carrier?
Glutamine
What is the pathway for glutamine synthesis?
Glutamate + NH3 (glutamine synthetase)
What is the major gluconeogenic amino acid?
Alanine
Alanine converts some of its atoms into specific compounds. Name the compounds as well as what was used to make them.
N - urea & ketone bodies. C - glucose.
Where is alanine processed in the body?
The liver
Glutamate collects nitrogen from other amino acids via what kind of reaction?
Transamination
At physiological pH are you more likely to find NH4+ or NH3?
NH4+
Which molecule can cross the cell membrane, NH4+ or NH3?
NH3
What are 3 major reactions regarding the fate of ammonium that occur in all cells?
- glutamate dehydrogenase/synthase
- glutamine synthetase
- carbamoyl-phosphate synthetase I
What 3 body parts provide sources of NH4 for the urea cycle?
Brain, muscle, gut
The brain and muscle both produce the same molecule that provides NH4 for the urea cycle. What is this molecule, and how is it produced?
Fumarate from aspartate in the purine nucleotide cycle.
The gut provides NH4 for the urea cycle via what molecule(s)?
Breakdown of various amino acids.
Define transamination.
Transfer of an amino group from an alpha-amino acid to an alpha-keto acid.
In amino acid biosynthesis, the ______ of ______ is transferred to various _____ acids generating _____ acids.
…..amino group…..glutamate…..alpha-keto…..alpha-amino…..
Transamination reactions are reversible. Is this true?
Yes
What cofactor is used for transamination reactions? What is it known as?
Pyridoxal phosphate (PLP) - transaminase or aminotransferase enzyme
Transamination reactions generate what 2 molecules in amino acid catabolism?
Glutamate or aspartate
What amino acids are essential to humans?
PVT TIM HALL
phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, alanine, lysine, leucine
What is similar about the 3 branched chain amino acids regarding degredation?
Same 3 enzymes catalyze the 1st 3 steps in all pathways.
What are the branched amino acids?
leucine, valine, isoleucine
What is the basic mechanism for branched-chain amino acid degredation?
Branched AA —–> (br. chain AA transaminase) alpha-keto acid —–> (br. chain alpha-keto acid dehydrogenase) —–> Acetyl CoA or Succinyl CoA
Do amino acids make products other than proteins?
Yes - glutathione, glycine, methionine, purines, bile salts, heme, creatine phosphate, etc.
What is NO?
Nitric oxid -gas hormone which can diffuse rapidly in cells. It is also a messenger that activates gCMP synthesis.
What does NO do?
Relaxes blood vessels, lowers BP, and is a neurotransmitter to the brain.
How is NO Synthesized?
From arginine
What happens when you have high levels of NO during a stroke?
Kill neurons.
What is the glucose/alanine cycle?
Exchange glucose and alanine between muscle and liver.
What is the purpose of the glucose/alanine cycle?
It provides an indirect means for muscle to eliminate N (and pyruvate, if necessary) and replenish its energy supply.
Amino acid degredation in the muscle leads to what?
The transfer of nitrogens to alpha-ketoglutarate and pyruvate.
How is the urea cycle regulated?
By substrate availability; this is a feed-forward regulation.
What is the basic mechanism of urea cycle regulation?
The presence of arginine stimulates the synthesis of NAG (N-acetylglutamate), which activates CPSI (carbamoyl phosphate synthetase I), which pushes the urea cycle forward at a faster rate.
What 2 reactions are stimulated by the increase of arginine levels in the liver?
Synthesis of NAG, and thus an increased rate at which carbamoyl phosphate is produced. Production of more ornithine, making the cycle operate more rapidly.
To what conditions that require increased protein metabolism does the induction of urea cycle enzymes respond?
High protein diet or prolonged fasting
What are the major enzymes of the urea cycle and where can they be found?
Mitochondrial matrix - CPSI, ornithine transcarbamoylase; cytosol - arginosuccinate synthetase, arginosuccinate lyase, arginase
What links urea to the TCA cycle?
Fumarate
What are the 5 steps of the urea cycle?
- Synthesis of carbamoyl phosphate
- Production of arginine by the urea cycle
3,4. Conversion of citrulline to arginine - Cleavage of arginine to produce urea
What are the main products of the urea cycle that exist in the mitochondrial matrix?
carbamoyl phosphate & citrulline
What are the main products of the urea cycle that exist in the cytosol?
arginine, urea, ornithine
What is a metabolic emergency caused by ammonia?
Hyperammonemia
When a urea cycle enzyme is defective, you get an accumulation of urea cycle intermediates. This causes levels of what molecule to increase in the circulation?
Glutamine
If there’s not a enough glutamine, then what levels are also being decreased? What does this lead to?
Alpha-ketoglutarate levels are too low to fix more free ammonia, leading to elevated levels of ammonia in the blood.
What would you expect to see if there are defects in any urea-cycle enzyme?
Elevated glutamine and ammonia levels in circulation
What drugs can you use to help excrete excess nitrogen?
Benzoic acid and phenylbutyrate
Explain the mechanisms of benzoic acid and phenylbutyrate.
Benzoic acid - after activation it reacts with glycine to form hippuric acid, which is excreted. Phenylbutyrate - oxidation product phenylacetate forms conjugate with glutamine and is excreted.
