Metabolism - Amino Acid Metabolism

Question 0

What amino acids may become essential under certain conditions?

Answer 0

Histidine
Cysteine
Arginine
Tyrosine

Question 1

What are the essential amino acids?

Answer 1

Leucine
Lysine
Isoleucine
Tryptophan
Methionine 
Threonine
Valine
Phenylalanine

Question 2

What is the nitrogen balance in health, starvation and pregnancy?

Answer 2

Health - 0 N balance
Pregnancy - + N balance
Starvation - - N balance

Question 3

How much protein does the average person carry?

Answer 3

6kg which holds ~ 100000kj energy

Question 4

How is nitrogen taken in, used and lost in the body?

Answer 4

Taken in via diet
Used to form N compounds (a/a, bases) and proteins
Lost via hair, nails a s as waste products in the urine.

Question 5

How is protein broken down?

Answer 5

Protein to amino acids.
Amino acids to amino group and C skeleton
C skeleton to products for gluconeogenesis or ketone body formation.

Question 6

How can amino groups be removed in protein metabolism?

Answer 6

1). Transamination - the amino group is transferred to a keto acid

–> ALT (alanine aminotransferase) converts alanine to glutamate (uses alphaketoglutarate)

–> AST (aspartate aminotransferase) converts glutamate to aspartate (uses oxaloacetate)

2) . Deamination is the removal of the amino group to form NH3, which is then converted to NH4+
- -> NH4+ is toxic so needs removing via conversion to glutamine or urea.

Question 7

Where does the urea cycle occur and how many enzymes does it require?

Answer 7

Liver

5 enzymes

Question 8

What a the basics of the urea cycle?

Answer 8

Glutamate is converted to aspartate and fed into the cycle. 2ATP, CO2 and NH3 are also fed in from the mitochondrial matrix. Urea is produced.

Question 9

What are the effects of complete/partial loss of an enzyme in the urea cycle?

Answer 9

Complete = fatal.

Partial = hyperammonoemia and accumulation/excretion of the product. Leads to the symptoms of NH3 toxicity (vomiting, blurred vision, tremor, coma) and is managed by a low protein diet with amino acids replaced by keto acids.

Question 10

Where is ammonia produced?

Answer 10

In deamination

Question 11

Why is ammonia toxic?

Answer 11

It has pH effects (alkali)
Affects neurotransmitter synthesis
Reduces TCA activity by reacting with alpha-ketoglutarate = produces glutamate and disrupts energy supply to cell.

Question 12

How does the body detoxify ammonia?

Answer 12

NH3 + ATP + glutamate —-> glutamine

Glutamine is used to synthesise N containing compounds
OR
Released from cells and transported via blood to:
Kidneys for excretion
Liver to be put into urea
Where it is broken back into ammonia by glutaminase.

Question 13

What is happening in phenylketonuria?

Answer 13

1). Phenylalanine hydroxylase is missing = can’t convert phenylalanine to tyrosine = no dopamine, adrenaline or noradrenaline can be made.

2). Takes alternative pathway to give phenylpyruvate.
= phenylalanine and phenylpyruvate build up

Question 14

Why is the build up of phenylpyruvate and phenylalanine a problem in phenylketonuria?

Answer 14

Phenylpyruvate - inhibits uptake of pyruvate into mitochondria so glucose isn’t metabolised well = brain damage as brain can only use glucose.

Phenylalanine - competes with other a/a to use the transporter to cross the blood brain barrier = starves brain of others = mental retardation.

Question 15

How is phenylketonuria treated?

Answer 15

Tyrosine supplements

Diet low in phenylalanine

Question 16

What parts of the body does homocystinuria affect and why?

Answer 16

The CVS, CNS, CT and muscles as it affects fibrillin1

Question 17

What cofactors does the enzyme CBS require?

Answer 17

VitB6

Question 18

What happens in homocystinuria?

Answer 18

1). CBS enzyme is missing so which normally produces cystathionine and therefore cysteine.

2). Homocysteine therefore enters another pathway which requires VitB12 and produces methionine.
= methionine and homocysteine build up

Question 19

What damage does homocysteine and methionine build up in homocystinuria cause?

Answer 19

Methionine - competes with other a/a to cross blood brain barrier of brain = mental retardation

Homocysteine - binds to Lys residues in fibrillin1 protein, altering the proteins shape. This gives certain characteristics:

• tall
• gangly
• lens dislocation in eye

Question 20

What gas signalling molecules are produced during amino acid metabolism and what are their roles?

Answer 20

1) . Arginine—>NO
- vasodilator
- neurotransmitter
- inflammatory mediator

2) . Cysteine—>H2S
- vasodilator
- neuromodulator
- anti inflammatory?

Question 21

How is creatine produced and how is this useful?

Answer 21

Produced by a spontaneous reaction at a constant rate in amino acid metabolism (unless muscle is wasting).

It is excreted via kidneys, and as creating excretion per 24h is proportional to muscle mass, the conc in urine can be measured to give an indication of urine dilution and muscle mass.