L6 - Amino Acid Metabolism Flashcards
Explain how amino acids are classified as essential or nonessential and the significance of this classification:
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.
Function of amino acids:
- Building blocks of proteins
- Can be used as neurotransmitters or can be used to produce haem, purines and pyrimides (for DNA & RNA synthesis), creatine and carnitine
- Can be used as a source of glucose (gluconeogenesis) in starvation and fasting state
Protein Turnover:
Average turnover, is this variable, what is protein turnover, give examples of half-lives of some types of proteins.
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.
Amino acid Pool:
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.
Protein Requirements:
- 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.
Essential Amino Acids:
- 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)
Nitrogen Balance:
In normal healthy adult, the total amount of N intake is equal to the amount of N excreted.
i.e. Protein Synthesis = Protein Breakdown
Positive Nitrogen Balance:
N (intake) > N (excretion)
Protein Synthesis > Protein Breakdown
This is seen in:
- In normal growth of children
- In recovery after illness
- After immobilisation from accident
- In pregnancy
Negative Nitrogen Balance:
N (intake) < N (excretion)
Protein Synthesis < Protein Breakdown
This is seen in:
- In illness
- In injury and trauma
- In cancer
- In starvation
If this is prolonged, it can lead to loss of essential body tissues - leads to death.
Pathways of Protein Degradation:
- Main cellular Proteins
- Foreign Extrinsic Proteins
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.
Amino acid Degradation:
Amino acid has to remove amino group for it to be degraded.
Amino Acid —-> Keto Acid + Ammonia (NH2)
Transamination:
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).
Deamination:
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+
Transdeamination:
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)
Fate of keto acids:
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).
What is glucogenic and ketogenic a.a. and give examples of the latter?
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.
Role of the Liver in N metabolism:
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)
Transport of amino groups to liver:
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)
Glutamine metabolism:
In muscles: (glutamate –> glutamine)
Glutamate + NH3 + ATP –> Glutamine + ADP + Pi
Uses GLUTAMINE SYNTHETASE.
In liver: (glutamine –> glutamate)
Glutamine + H2O –> Glutamate + NH3
Uses GLUTAMINASE
Importance of Glutamine:
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+)
The Process of Urea Cycle:
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.
End Products of Nitrogen Metabolism:
1) Urea from protein breakdown
2) Creatine from phosphocreatine breakdown
3) Uric acid from DNA and RNA breakdown
4) Ammonia - control of body pH
Why is ammonia neurotoxic?
- ammonia is neurotoxic
- causes cerebral oedema, coma and death
- causes cell death
What is hyperammonaemia and what are its causes:
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
