Urea cycle Flashcards
(31 cards)
What protects an amino acid?
Its amine group
Can we use amino acids for things other than the production of proteins (energy, etc)?
No, unless we get rid of the amino group
What is an alpha-keto acid?
The amino acid, when we remove the amine group from it, a-keto acid can be used in other metabolic pathways
Alanine is converted to what a-keto acid when we remove the amino group from it?
Pyruvate (end-product of glycolysis)
Aspartate is converted to what a-keto acid when we remove the amino group from it?
Oxaloacetate (Intermediate of TCA cycle)
Glutamate is converted to what, a-keto acid when we remove the amino group from it?
a-ketoglutarate (Intermediate of TCA cycle)
Do we have the enzyme that deaminates all of the amino acids?
No, we only have deaminases of glutamate (glutamate dehydrogenase)
How do we convert amino acids into energy?
- Since we do not have the enzyme that directly deaminates amino acids, we have transamination, where it transfers an amino group from one amino acid to an a-keto acid (converting an amino acid to a a-keto acid and the a-keto acid to an amino acid)
- Since we have glutamate dehydrogenase, we will convert the Amino acid to its a-keto acid and convert a-ketoglutarate to glutamate (since it is readily converted to its a-keto acid “the enzyme is available”)
What is the enzyme that catalyzes the transfer of an amino group from an amino acid to an a-keto acid?
Transaminases (aspartate transaminase, alanine transaminase)
- Glutamate has a special one (glutamate dehydrogenase)
What is the fate of the carbon skeleton of the deaminated amino acids?
1) Catabolized for energy
2) Used to synthesize glucose
3) Fatty acids for energy storage
How does our body get rid of the amino group?
- Two mechanisms are available to transport ammonia from the peripheral tissues to the liver and then for its ultimate conversion to urea
1) The first mechanism is to form glutamine from the addition of ammonia to glutamate via glutamine synthase (the amino group will be added to the R-chain)
- Glutamine is transported in the blood to the liver, where it is cleaved by glutaminase to produce glutamate and a free ammonia; ammonia is converted to urea
2) Formation of alanine by the transamination of pyruvate (produced by aerobic glycolysis), alanine is then transferred to the liver by the blood to get converted back to pyruvate via transamination
What is the fate of the pyruvate when we convert alanine to pyruvate in the liver via transamination?
1) Glucose synthesis, which goes to the muscle via the blood in a pathway called the glucose-alanine cycle
What is the function of glutamate dehydrogenase?
It catalyzes the reversible reaction of glutamate deamination and a-ketoglutarate amination
What is the fate of ammonia?
Ammonia is extremely toxic, and if left free, it can damage our bodies; and thus, it is converted to urea
- Although urea is also toxic, it is not compared to ammonia + each urea contains 2 ammonia group
In which cell compartments does the urea cycle take place?
1) Mitochondria
2) Cytoplasm
In which organ does the urea cycle occur?
The liver
What is the rate-limiting step in the synthesis of urea?
- The first step, catalyzes 2 ATP (the only single reaction that catalyzes 2 ATP, according to Dr. Waseem’s knowledge)
- It is the addition of ammonia to carbon dioxide using 2 ATPs via Carbamoyl phosphate synthetase 1, INTO carbamoyl phosphate + 3H+, 2ADP, and a single phosphate
- N-acetyl-glutamate is an allosteric activator of this enzyme (carbamoyl phosphate synthetase 1)
How many reactions are there in the urea cycle?
7
What are the steps of the urea cycle?
- Mitochondria
1) Conversion of CO2 + NH3 (+ 2ATP) into carbamoyl phosphate via carbamoyl phosphate synthetase 1 (the rate limiting step)
2) Interaction of carbamoyl phosphate with l-ornithine in the mitochondria to produce l-citrulline via the enzyme ornithine transcarbamoylase
- Citruline will then be antiported into the cytoplasm, and l-ornithine will go into the mitochondria
- Cytoplasm
3) Citrulline will join with aspartate to get the second ammonia to form argininosuccinate, which is catalyzed via argininosuccinate synthase (consumes an ATP)
4) Argininosuccinate will get lysed (removing fumarate from it) to form arginine via argininosuccinate lyase
5) Arginase will then remove urea from arginine, forming ornithine (which will get antiported into the mitochondria
What will happen if we have ornithine trans-carbamoylase deficiency?
1) Carbamoyl phosphate will accumulate, which will move into the cytoplasm
2) Carbamoyl phosphate is a product of another reaction produced by CPS-2
3) Once the carbamoyl phosphate accumulates in the cytoplasm it will get integrated into another pathway (the pyrimidine pathway, and it will not go through the whole 6 reaction), it will stop at reaction 4 by the formation of (rotate)
4) Orotate will start accumulating in the kidneys, and the kidneys will excrete it in urine leading to (oritic aciduria)
5) Type-2 hyperammonemia (most common disorder of the urea cycle)
What enzyme is deficient in type-1 hyperammonemia?
Carbamoyl phosphate synthetase-1
What enzyme is deficient in Type-2 hyperammonemia?
Ornithine transcarbamoylase
Regarding the urea cycle, which enzyme is found in the mitochondria?
Ornithine trans-carbamylase (a lot of references don’t consider the formation of carbamoyl phosphate part of the urea cycle)
What are the enzymes of the urea cycle are found in the cytosol?
1) Arginino succinate synthase
2) Argininosuccinase
3) Arginase
- For each cycle, citrulline must leave the mitochondria, and
ornithine must enter the mitochondrial matrix - An ornithine/citrulline transporter in the inner mitochondrial membrane facilitates transmembrane fluxes of citrulline & ornithine
