Amino acid metabolism

Question 1

Why do we have amino acid metabolism

Answer 1

Incorporate ammonium ion into our body as we cannot absorb nitrogen from the air

Question 2

Alpha ketoglutarate function

Answer 2

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.

Question 3

Formation of glutamine from glutamate

Answer 3

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

Question 4

Formation of glutamate from glutamine

Answer 4

L-glutamine is converted to L-glutamate via glutaminase. H2O is added and NH4 ion is released.
This is non-reversible.

Question 5

Alpha ketoglutarate structure

Answer 5

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.

Question 6

Glutamate structure

Answer 6

Same as alpha ketoglutarate, but the carbonyl group C=O is changed to a CH, H3N+, where there are 2 chemicals groups now.

Question 7

Glutamine structure

Answer 7

Same as glutamate, but COO- group further away from the CH-H3N+ becomes C=O, NH2, where there is 2 chemical groups

Question 8

Formation of pyruvate from glutamine

Answer 8

Glutamate acts a amino group donor for other amino acid synthesis.

Pyruvate + Glutamate is converted into Alanine and Alpha ketoglutarate via alanine transaminase ALT.

Question 9

Transamination

Answer 9

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.

Question 10

Synthesis of aspartate from oxaloacetate

Answer 10

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

Question 11

Synthesis of asparagine from aspartate

Answer 11

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

Question 12

Oxaloacetate chemical structure

Answer 12

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

Question 13

Synthesis of alanine from pyruvate

Answer 13

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

Question 14

Structure of pyruvate

Answer 14

3 carbon molecule where 1 carbon is COO-, 1 carbon is carbonyl group and last carbon is CH3

Question 15

Where do amino acid synthesis link to TCA cycle?

Answer 15

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

Question 16

Amino Acid degradation

Answer 16

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

Question 17

Transamination and glutamate

Answer 17

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

Question 18

How glutamate is formed from reverse transanimation

Answer 18

Aspartate and alpha-ketoglutarate becomes oxaloacetate and glutamate via aspartate transaminase

Alanine and alpha ketoglutarate become pyruvate and glutamate via alanine transaminase

Question 19

What happens to the degradation products of amino acid?

Answer 19

1. 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
2. Excretion
   Excess nitrogen is converted to urea

Question 20

What is oxidative deamination?

Answer 20

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+.

Question 21

Glutamate dehydrogenase

Answer 21

• 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

Question 22

What is transamination

Answer 22

the transfer of an amino group from one molecule to another

Question 23

Urea cycle

Answer 23

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.

Question 24

5 Steps of urea cycle

Answer 24

1. 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.
2. Carbamoyl phosphate and ornithine is converted to citrulline via ornithine transcarbamoylase, the carbamoyl phosphate group is donated to ornithine and releases 1 phosphate group.
3. 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.
4. Argininosuccinate is cleaved by argininosuccinase to form arginine and fumarate
5. 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

Question 25

Overall reaction of urea cycle

Answer 25

NH3 + CO2 + aspartate + 3 ATP + 3 H2O → Urea + fumarate + 2 ADP + 2 Pi + AMP + PPi + H2O

Question 26

Why turn ammonia to urea

Answer 26

Our body turns it into non-toxic, water-soluble UREA.

Urea is:
synthesized in the liver
disposed of in the urine
Low toxicity (as it has to be transported in blood from liver to kidneys)

Question 27

Structure of urea

Answer 27

1 carbon molecule, =O, -NH2, H2N with 3 chemical groups

C=O comes from CO2.
1 NH2 comes from Aspartate
Aspartate is derived from transamination with oxaloacetate and glutamate
1 H2N come from ammonia.
Fumarate and arginine is produced. Fumarate links urea cycle to Kreb cycle.

Step 1 and 2 occurs in mitochondrion and Step 3-5 occurs in cytosol.

Question 28

Phenylketonuria Description

Answer 28

Autosomal recessive metabolic disorder caused by deficiency of liver enzyme phenylalanine hydroxylase.

It prevents normal metabolism of phenylalanine, one of the essential amino acids that cannot be manufactured by the body and must therefore be consumed in protein rich foods.

Untreated individuals may give off a musty odor and they excrete large amounts of phenylalanine in their urine.

Phenylalanine is transaminated to phenylpyruvate, which is the abnormal pathway.

Accumulation of phenylalanine and phenylpyruvate can lead to brain damage.

Question 29

Symptoms of phenylketouria

Answer 29

If left undiagnosed or untreated initially :
Intellectual disability
Delayed development
Neurological problems (ex. Seizures)
Eczema
Musty odour in urine and breath
Lighter skin and hair (melanin production is less due to no phenylalanine which is related to tyrosine and tyrosine produces melanin)

Question 30

Management of PKU

Answer 30

Mostly managed through diet which involves:
elimination of high protein foods, such as milk, dairy products, meat, fish, chicken, eggs, beans, and nuts
special phenylalanine-free formula which contains protein, vitamins, minerals and energy with no phenylalanine

Pregnant women who have PKU should be extra careful with their phenylalanine intake

Question 31

Pathway of phenylalanine in the body

Answer 31

In the normal pathway, phenylalanine is converted to tyrosine via phenylalanine hydroxylate. Tyrosine can go on to form fumarate which can form oxaloacetate and acetoacetate which can form acetyl CoA. Tyrosine is a non-essential amino acid as the body can convert phenylalanine to tyrosine.

In the abnormal pathway, phenylalanine is transaminated to phenylpyruvate via phenylalanien transaminase. Alpha ketoglutarate accepts a amino group from phenylalanine C=O bond to form glutamate.