Amino acid metabolism Flashcards
(31 cards)
Why do we have amino acid metabolism
Incorporate ammonium ion into our body as we cannot absorb nitrogen from the air
Alpha ketoglutarate function
It accepts ammonium ion to form Glutamate via glutamate dehydrogenase. It is a reversible reaction. Glutamate + H2O is converted into alpha ketoglutarate + NH4, where NAD+ is converted into NADH and H+.
Glutamate dehydrogenase incorporates free ammonium ions into α-ketoglutarate to produce glutamate by reversing oxidative deamination (see Fig. 12-4). Glutamate then serves as a source of nitrogen by transamination with pyruvate to make alanine, and OAA to make aspartate.
This is reversible.
Formation of glutamine from glutamate
Glutamate is converted into glutamine via glutamine synthetase with the incorporation of a NH4 ion, where ATP is converted into ADP + Phosphate group.
This is non-reversible
Formation of glutamate from glutamine
L-glutamine is converted to L-glutamate via glutaminase. H2O is added and NH4 ion is released.
This is non-reversible.
Alpha ketoglutarate structure
It is a 5 carbon molecule with 2 Carbon being COO- groups. The other 2 carbon is CH2. The final carbon is a carbonyl group C=O at the 4th carbon.
Glutamate structure
Same as alpha ketoglutarate, but the carbonyl group C=O is changed to a CH, H3N+, where there are 2 chemicals groups now.
Glutamine structure
Same as glutamate, but COO- group further away from the CH-H3N+ becomes C=O, NH2, where there is 2 chemical groups
Formation of pyruvate from glutamine
Glutamate acts a amino group donor for other amino acid synthesis.
Pyruvate + Glutamate is converted into Alanine and Alpha ketoglutarate via alanine transaminase ALT.
Transamination
Transamination interconverts pairs of amino acids and alpha keto-acids
Amino acids can be converted into alpha keto acids and vice versa
Transferases are used to transfer amino group from most amino acids and produce the corresponding alpha-keto acid, the cofactor is pyridoxal phosphate, an active form of vitamin B6.
Synthesis of aspartate from oxaloacetate
Oxaloacetate is converted to aspartate via aspartate transaminase
Oxaloacetate is the alpha keto acid of aspartate
Glutamate donates a amino group to oxaloacetate in the process to form alpha ketoglutarate, it gains a =O carbonyl group in the process
The O in the carbonyl group is replaced by NH3+, basically they swap the C=O with NH3+ on both of the amino acids
Synthesis of asparagine from aspartate
Aspartate is converted to asparagine via asparagine synthetase. Glutamine donates a H2N which is near its COO-, and replace it with O- to form glutamate. ATP is converted into AMP + 2 Phosphate ions in the process.
Asparagine is basically a aspartate with one of its COO- replaced with C=O and H2N, 2 chemical groups
Oxaloacetate chemical structure
4 carbon molecule with 2 carbon at both ends with COO-
One carbon is in a carbonyl group C=O
The last carbon is CH2
Synthesis of alanine from pyruvate
Pyruvate is the alpha keto acid of alanine
Glutamate and pyruvate is converted into alanine and alpha-ketoglutarate via alanine transaminase
This reaction is reversible
Glutamate donates a NH2 to pyruvate where its C=O bond is converted to C-NH2 bond.
The glutamate HC-NH2 is converted to C=O to become alpha ketoglutarate.
Alanine is basically pyruvate where the O in C=O is converted to C-NH2
Structure of pyruvate
3 carbon molecule where 1 carbon is COO-, 1 carbon is carbonyl group and last carbon is CH3
Where do amino acid synthesis link to TCA cycle?
Amino acid synthesis via TCA cycle, other chemicals like fumarate and succinate can also be converted to amino acids
Alpha ketoglutarate to glutamate synthesis is reversible
Oxaloacetate to aspartate synthesis is also reversible
Amino Acid degradation
Only excess amino acids are degraded and the major site of amino acid degradation is the liver
Step 1: Transamination
Catalyzed by transaminases in the liver and other tissues
Step 2: Oxidative deamination
Catalyzed by glutamate dehydrogenase
Transamination and glutamate
Most amino acids do not form ammonia directly (except glutamate)
They have to transfer alpha-amino group to alpha-ketoglutarate to form glutamate.
Reversible reaction. Catalyzed by transaminase.
All transaminases contains pyridoxal phosphate, coenzyme form of vitamin B6
How glutamate is formed from reverse transanimation
Aspartate and alpha-ketoglutarate becomes oxaloacetate and glutamate via aspartate transaminase
Alanine and alpha ketoglutarate become pyruvate and glutamate via alanine transaminase
What happens to the degradation products of amino acid?
- Synthesis
Amino group and other nitrogen compounds can be used to synthesize other amino acids and other nitrogen containing compounds such as purines and pyrimidines - Excretion
Excess nitrogen is converted to urea
What is oxidative deamination?
Glutamate release its amino group to the liver
In hepatocytes(chief liver cells), glutamate is transported from cytosol into mitochondria, where it undergoes oxidative deamination by glutamate dehydrogenase to form alpha ketoglutarate.
It occurs primarily on glutamic acid as it is the end product of many transamination reactions.
The α-amino group of many amino acids is transferred to α-ketoglutarate to formglutamate,which is then oxidatively deaminated to yield ammonium ion (NH4+).
This reaction is catalyzed byglutamate dehydrogenase.This enzyme is unusual in being able to utilize eitherNAD+ orNADP+.
Glutamate dehydrogenase
- The glutamate dehydrogenase is allosterically controlled by ATP and ADP.
- ATP acts as an inhibitor whereas ADP is an activator.
- This enzyme is unusual in being able to utilize eitherNAD+ orNADP+, to produce NADH and NADPH
What is transamination
the transfer of an amino group from one molecule to another
Urea cycle
Convert toxic ammonia or ammonium produced from deamination to urea
the entire process converts two amino groups, one from NH+4 and one from Aspartate, and a carbon atom from HCO−3, to the relatively nontoxic excretion product urea. This occurs at the cost of four “high-energy” phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP). The conversion from ammonia to urea happens in five main steps. The first is needed for ammonia to enter the cycle and the following four are all a part of the cycle itself. To enter the cycle, ammonia is converted to carbamoyl phosphate. The urea cycle consists of four enzymatic reactions: one mitochondrial and three cytosolic. This uses 6 enzymes.
5 Steps of urea cycle
- Before the urea cycle begins ammonia is converted to carbamoyl phosphate. The reaction is catalyzed by carbamoyl phosphate synthetase I and requires the use of two ATP molecules. The carbamoyl phosphate then enters the urea cycle.
- Carbamoyl phosphate and ornithine is converted to citrulline via ornithine transcarbamoylase, the carbamoyl phosphate group is donated to ornithine and releases 1 phosphate group.
- A condensation reaction occurs between the amino group of aspartate and the carbonyl group of citrulline to form argininosuccinate. This reaction is ATP dependent and is catalyzed by argininosuccinate synthetase. ATP becomes AMP + 2 phosphate groups.
- Argininosuccinate is cleaved by argininosuccinase to form arginine and fumarate
- Arginine is cleaved by arginase to form urea and ornithine. The ornithine is then transported back to the mitochondria to begin the urea cycle again
