L6 - Amino Acid Metabolism

Question 1

Explain how amino acids are classified as essential or nonessential and the significance of this classification:

Answer 1

Essential amino acids can’t be synthesised in our body - only found in diet.

Non-essential amino acids can be synthesised in our body (through transamination). Carbon skeleton can be made in body and can use amino group of other a.a.

Question 2

Function of amino acids:

Answer 2

1. Building blocks of proteins
2. Can be used as neurotransmitters or can be used to produce haem, purines and pyrimides (for DNA & RNA synthesis), creatine and carnitine
3. Can be used as a source of glucose (gluconeogenesis) in starvation and fasting state

Question 3

Protein Turnover:

Average turnover, is this variable, what is protein turnover, give examples of half-lives of some types of proteins.

Answer 3

Average protein turnover: 300-400g per day
This is variable - depends on diet and exercise.

Body protein can be degraded and re-synthesised - turnover.

Most cellular proteins have a half-life of a few days.
Structural proteins e.g. collagen has a half life of years.
Hormones and enzymes have a high life of minutes.

Question 4

Amino acid Pool:

Answer 4

This is a small quantity of free a.a. in bloodstream and tissues. Have limited store in muscles.

This is unlike glucose and fats which can be stored in large amounts in our tissues.

a.a can mix and exchange between pools.

Question 5

Protein Requirements:

Answer 5

• No storage form of protein
• Have to be taken from diet to replace aa lost and for tissue repair.
• recommended amount: 50-70g
• Excess a.a are catabolised and ammonia is converted to urea and excreted as urine.

Question 6

Essential Amino Acids:

Answer 6

• Have 20 a.a - we can produce 10 of these. The other 10 are EAA which comes from the diet.

Isoleucine
Leucine
Threonine
Histidine
Lysine
Methionine
Phenylalanine
Tryptophan
Valine
(Arg)

Question 7

Nitrogen Balance:

Answer 7

In normal healthy adult, the total amount of N intake is equal to the amount of N excreted.

i.e. Protein Synthesis = Protein Breakdown

Question 8

Positive Nitrogen Balance:

Answer 8

N (intake) > N (excretion)
Protein Synthesis > Protein Breakdown

This is seen in:

1. In normal growth of children
2. In recovery after illness
3. After immobilisation from accident
4. In pregnancy

Question 9

Negative Nitrogen Balance:

Answer 9

N (intake) < N (excretion)
Protein Synthesis < Protein Breakdown

This is seen in:

1. In illness
2. In injury and trauma
3. In cancer
4. In starvation

If this is prolonged, it can lead to loss of essential body tissues - leads to death.

Question 10

Pathways of Protein Degradation:

• Main cellular Proteins
• Foreign Extrinsic Proteins

Answer 10

Main Cellular Proteins:
- If old/damaged proteins, this can be degraded by ubiquitin proteosomal system.

Foreign Extrinsic Protein:
- If old/damaged organelle, it can undergo endocytosis or autophagocytosis. This then fuses with lysosomes and is degraded into a.a by proteolytic enzymes.

Starvation and hormones e.g. cortisol increases rate of protein breakdown.

Question 11

Amino acid Degradation:

Answer 11

Amino acid has to remove amino group for it to be degraded.

Amino Acid —-> Keto Acid + Ammonia (NH2)

Question 12

Transamination:

Answer 12

Transamination - transfers amino group from amino acid (1) to keto acid (2) to form a new amino acid (2) and new keto acid (1).

Alanine + α-ketoglutarate –> Pyruvate + Glutamate

This uses aminotransferase. All aminotransferases have a prosthetic group (Vit B6 - pyridoxal phosphate; this carries amino group).

Question 13

Deamination:

Answer 13

Deamination - removes amino group from amino acids (leaves behind keto acid) and this is converted to urea and excreted through urine.

Only glutamate can be deamination - as only have glutamate dehydrogenase.

Glutamate + NAD —-> α-ketoglutarate + NADH + H + NH4+

Question 14

Transdeamination:

Answer 14

For deamination of an a.a. to occur, transamination of a.a has to occur in order to pass NH2 to glutamate. This can then be deaminated in liver to remove amino group.

Transamination - in liver and muscle
Deamination - in liver (+ kidney)

Question 15

Fate of keto acids:

Answer 15

If glucogenic, keto acids can be converted to glucose via gluconeogenesis and can either be metabolised to CO2 and H2O (FASTED) or can be stored as glycogen (FED).

If ketogenic, keto acids are converted to acetyl CoA. This can either be metabolised to CO2 and H2O (FASTED) or can be used to produce FAs (FED).

Question 16

What is glucogenic and ketogenic a.a. and give examples of the latter?

Answer 16

Glucogenic - carbon skeleton of a.a. can be converted to glucose

Ketogenic - carbon skeleton of a.a. can be converted to acetyl CoA

Examples of ketogenic a.a - Leucine and Lysine.
Phe and Tyr (Trp and Leu) are both ketogenic and glucogenic.

Question 17

Role of the Liver in N metabolism:

Answer 17

1) It takes amino acids, glucose and fats from portal circulation
2) Can synthesise cellular proteins with a.a
3) Synthesis of plasma proteins (e.g. albumin, clotting factors, etc.)
4) Synthesis of haem, purines and pyrimidines (for DNA & RNA)
5) Excess a.a. can be degraded by transdeamination
6) Conversion of NH3 to urea for excretion (urea cycle)

Question 18

Transport of amino groups to liver:

Answer 18

Liver is the only organ which can do deamination and remove the amino group via urea cycle. Muscles constantly do protein breakdown so a.a. have to be transferred to liver for further breakdown.

This is done by Glutamine which carries 2 amino groups to liver.

Other important a.a are glutamine, glutamate, aspartate and alanine (involved in amino transport in blood)

Question 19

Glutamine metabolism:

Answer 19

In muscles: (glutamate –> glutamine)
Glutamate + NH3 + ATP –> Glutamine + ADP + Pi
Uses GLUTAMINE SYNTHETASE.

In liver: (glutamine –> glutamate)
Glutamine + H2O –> Glutamate + NH3
Uses GLUTAMINASE

Question 20

Importance of Glutamine:

Answer 20

1) It is a safe carrier of amino groups in blood (ammonia is toxic)
2) It can carry 2 amino groups to liver for urea formation
3) it can take ammonia to kidney for pH regulation (buffers H+)

Question 21

The Process of Urea Cycle:

Answer 21

CO2 + NH3 + 2ATP –> Carbamoyl Phosphate + 2ADP + Pi
Uses CARBAMOYL PHOSPHATE SYNTHASE

Carbamoyl phosphate + Ornithine –> Citrulline
ORNITHINE TRANSCARBAMOYLASE

Citrulline + Aspartate –> Argininosuccinate
ARGININOSUCCINATE SYNTHASE

Argininosuccinate –> Arginine + Fumarate
ARGININOSUCCINASE

Arginine –> Urea + Ornithine
ARGINASE

The two amino groups come from carbamoyl phosphate (i.e. Glu) and Asp.

Question 22

End Products of Nitrogen Metabolism:

Answer 22

1) Urea from protein breakdown
2) Creatine from phosphocreatine breakdown
3) Uric acid from DNA and RNA breakdown
4) Ammonia - control of body pH

Question 23

Why is ammonia neurotoxic?

Answer 23

• ammonia is neurotoxic
• causes cerebral oedema, coma and death
• causes cell death

Question 24

What is hyperammonaemia and what are its causes:

Answer 24

This is impaired conversion of NH3 to urea.

Caused by liver failure:
- due to cirrhosis, hepatitis, ischaemia, etc.

Caused by genetic defects:

• impaired activity of enzymes in urea cycle
• e.g. defective ornithine transcarbamoylase