Protein & amino acid metabolism

Question 1

Describe the pathway of protein turnover

Answer 1

Proteins are broken down into free amino acids. They can then either be used to synthesise cellular proteins or be sent to the liver.
When at the liver they are split into either the amino group or carbon skeleton.
The amino group is then excreted via the urea/urine pathway.

The carbon skeleton is either glucose in or ketogenic. Glucogenic will undergo gluconeogensis and ketogenic amino acids will form ketone bodies. These can both provide energy.

Question 2

Give an example of a glucogenic and ketogenic amino and an example of one that is both.

Answer 2

Glucogenic- e.g. aspartate and asparagine.

Ketogenic - lysine or leucine only 2

Both - tryptophan and threonine

Question 3

Explain how and why protein mobilisation occurs

Answer 3

This occurs during extreme starvation.
It is controlled completely by hormones.

Insulin and growth hormone increase the effect on protein synthesis and decrease the effect on protein degradation.
Glucocorticoids are the other way round.

Question 4

What disease causes an excessive breakdown of proteins?

Answer 4

Cushing disease - excess cortisol

It weakens structure of skin and leads to striae formation and centralised obesity.

Question 5

What is a peptide bond?

Answer 5

The bond between two amino acids - the OH part of the carboxyl group is removed and the H on the other amino group is removed so the 2 carboxyl/amino groups join. Water is a by product of this reaction.

Question 6

Where do the carbons for non essential amino acid synthesis come from?

Answer 6

Intermediates of glycolysis
Pentose phosphate pathway
Krebs cycle

Question 7

Where does the amino group come from in the in vivo synthesis of amino acids?

Answer 7

Provided by other amino acids via transamination or from ammonia

Question 8

Give 2 examples of amino acids specially needed for the synthesis of important compounds

Answer 8

Histidine - histamine
Typtophan - serotonin and melatonin

Question 9

What is transamination?

Answer 9

Where the amine group is transferred over to make a new amino acid. They are combined with a keto acid which also produces another keto acid during the process. This is catalysed by an amino transferase.

Question 9

What is transamination?

Answer 9

Where the amine group is transferred over to make a new amino acid. They are combined with a keto acid which also produces another keto acid during the process. This is catalysed by an amino transferase.

Question 10

What is the co-enzyme that all aminotransferases require and where does it come from?

Answer 10

Coenzyme pyridoxal phosphate and it is a derivative of vitamin B6

Question 11

What are 2 key aminotransferases and what do they do?

Answer 11

Alanine aminotransferase- catalyses the inter conversion of alanine and a-ketoglutarate to pyruvate and glutamate

Asparatate aminotransferase - catalyses the intercom version of aspartate and a-ketoglutarate to oxaloacetate and glutamate

Levels particularly high in. Risk hepatitis, autoimmune liver disease and toxic injuries e.g. death cap mushroom ingestion.

Question 12

What is deamination?

Answer 12

This frees the amino group as free amino. Occurs mainly in liver and kidneys. The keto acids can be used for energy but the ammonia must be excreted, converted to urea then urine.

Enzymes that can de-aminate amino acids include amino acid oxidases, glutamine’s and glutamate dehydrogenase.

Question 13

What are symptoms associated with defects in the urea cycle?

Answer 13

Dependent on nature of defect and amount of protein eaten. Including lethargy, vomiting, irritability, intellectual disability, seizures and coma.

Question 14

How do you manage a urea cycle defect?

Answer 14

A low protein diet and also replace amino acids in diet with keto acids.

Question 15

Explain ammonia toxicity effects

Answer 15

Disrupts cerebral blood flow, makes the blood alkali. Alteration of BBB, interferes with TCA cycle. Interference with metabolism of neurotransmitters e.g. GABA.

Question 16

How is amino acid nitrogen safely transported from the tissues to the liver for disposal?

Answer 16

1. Glutamine - ammonia combines with glutamate to form glutamine. Then transported in blood to liver or kidneys where it’s cleaved by glutamine to reform glutamate and ammonia. In liver, ammonia directly enters into urea cycle. In kidneys directly excreted as urine.
2. Alanine - amine group transferred to glutamate by transamination. Pyruvate then transamination by glutamate to form alanine. Alanine taken to liver and converted back to pyruvate by transamination. Then amino group fed into urea cycle via glutamate for disposal as urea. Pyruvate is used to synthesised glucose so gets fed back into the tissues.

Question 17

What are some things that they heel prick test screen for?

Answer 17

Sickle cell disease
Cystic fibrosis
Congenital hypothyroidism
Phenylketonuria
Homocystinuria
Maple syrup urine disease

Question 18

Describe the disease phenylketonuria e.g. causes, symptoms, treatment

Answer 18

Deficiency in phenylalanine hydroxylase. Autosomal recessive gene on chromosome 12.

Phenylalanine can’t be broken down into tyrosine by phenylalanine hydroxylase.
Phenylalanine gets transaminated to phenylpyruvate then Broken down into phenylketones which then Accumulate and are excreted via urine.

Symptoms- severe intellectual disability, developmental delay, microcephaly, seizures, hypopigmentation.

Treatment - low phenylalanine diet enriched with tyrosine. Avoid artificial sweeteners and high protein foods.

Question 19

What pathways can be affected due to a lack of tyrosine from the phenylketonuria disease?

Answer 19

Noradrenaline and adrenaline
Dopamine
Melanin
Thyroid hormones
General protein synthesis

Question 20

What is homocystinuria?

Answer 20

Protein methionine converted to homocysteine.
Normally would be converted to cyststhionine and then cysteine but a defect in cystathionine B-synthase means homocysteine builds up.
This enzyme also requires vit B6 as a cofactor.

Treatment: low methionine diet, avoid high protein foods and nuts which content methionine. Need cysteine and vitamin B 6&12 supplementation.