8 . Urea acid cycle (Lect 9) Flashcards
Urea cycle
What is the primary function of the urea cycle?
To convert ammonia (highly toxic) produced from oxidative deamination, into urea (less toxic)
Urea cycle
What would happen if ammonia is not converted into urea?
NH3 → NH4+ in the bloodstream. NH4+ can be diffused into the brain through the blood-brain barrier. NH4+ + glutamate → glutamine ; and glutamine absorbs water, causing the brain to cell and eventually cause death.
Urea cycle
Which organ does the urea cycle primarily occur?
In the liver and sometimes in the kidneys
Urea cycle
In which organelles does the urea cycle take place?
In the mitochondria and cytosol
Urea cycle
What is the overall equation for the formation of urea?
NH3 + HCO3- + Aspartate → Urea + fumarate
Urea cycle
NH3 + HCO3- + Aspartate → Urea + fumarate
How can fumarate be metabolised and utilised in other metabolic pathways?
Fumarate → malate
Malate → oxaloacetate (catalysed by malate deydrogenase)
* Oxaloacetate can then go through gluconegogenesis to generate glucose ;; or undergo the TCA cycle to generate energy (ATP)
Urea cycle
What is the first step in the urea cycle? (ammonia react w..)
NH3 + 2 ATP + HCO3- → carbamoyl phosphate + 2ADP + Pi
Urea cycle
In step 2 of the urea cycle, state the reaction that occurs (involving ornithine). What enzyme catalyzes the conversion of ornithine to its product?
Ornithine + carbamoyl phosphate → citrulline ;
catalysed by orthinine transcarbamylase
this reaction releases Pi
Urea cycle
Step 3 of urea cycle : citrulline reacts with ____ to be converted into ____, with the consumption of _____.
Aspartate
Arginosuccinate
ATP (which is converted to AMP + PPi)
Urea cycle
Urea cycle step 4 : What happens to arginino-succinate in the urea cycle?
It is converted to arginine with the release of fumarate
Urea cycle
What is the final step (step 5) of the urea cycle?
Hint : arginine → ?, releases ____?
Conversion of arginine back into ornithine, releasing urea
Urea cycle
State the equation of the first committed step of the urea cycle, and the enzyme that catalyses this reaction.
Ornithine + carbamoyl phosphate → citrulline + Pi
Enzyme : CPS synthase Type I
Urea cycle
How is carbamoyl phosphate synthase type I regulated? [2]
Through substrate channelling and allosteric regulation
Regulation
What is substrate channeling?
A process by which intermediate from one enzyme is transferred directly to the active site of another enzyme, without mixing with the bulk phase.
Regulation
What does substrate channeling enhance in metabolic pathways?
- Enzymatic efficiency
- Metabolic pathway rates
Regulation
What moelcule allosterically activates CPS type I? How is it formed, and what enzyme catalyses its synthesis?
N-acetylglutamate, formed from acetyl-CoA + glutamate ;;
catalysed by N-acetyl glutamate synthase
Regulation
Why does N-acetylglutamate increase the activity of carbamoyl phosphate synthase type I ?
High amino acid degradation leads to high glutamate levels (transamination), increasing the production of more N-acetylglutamate.
Since more amino acid degradation = need to remove more ammonia, NAG stimulates CPS I activity to enhance the rate of urea cycle in order to remove ammonia.
Regulation
How are the other steps in the urea acid cycle regulated?
By the concentration of substrates available
Synthesis of other compounds from AA
How are polyamines synthesized from amino acids?
Amino acids are converted into amines through decarboxylation ;;
these amines then undergo further decarboxylation and polymerisation to form polyamines
Synthesis of other compounds from AA
What is the role of polyamines in the cell?
Required for cell growth and proliferation
Synthesis of other compounds from AA
What do polyamines interact with?
Nucleic acids (polyanions);; since polyamines are cationic (NH3+
Fill in the blank: The urea cycle converts _______ into urea.
[ammonia]
True or False: Arginine is synthesized by the body for biosynthesis.
False. Arginine is synthesized to be used as a substrate in the urea acid cycle.
