Sesh 3- Protein and amino acid metabolism

Question 1

Which 2 hormones stimulate protein synthesis?

Answer 1

Insulin and growth hormone.

Question 2

What is the difference between a glucogenic and a ketogenic amino acid?

Answer 2

• Catabolism of glycogenic amino acids gives rise to products that can be used for gluconeogenesis
• Ketogenic amino acids get converted to acetyl CoA, so can be used to form ketone bodies

Question 3

How is most nitrogen in the body excreted?

Answer 3

As urea in urine and faeces

Question 4

Give 2 situations in which there would be a positive N balance in the body.

Answer 4

1. Active growth

2. Pregnancy

Question 5

Give 2 situations in which there would be a negative N balance in the body.

Answer 5

1. Malnutrition

2. Trauma

Question 6

Where do the C atoms required to form new amino acids come from?

Answer 6

Intermediates from:

• Glycolysis
• Kreb’s cycle
• Pentose phosphate pathway

Question 7

Where do the amino groups needed to synthesise amino acids come from?

Answer 7

Other amino acids via transamination

Question 8

Which 2 important signalling molecules are synthesised from amino acids?

Answer 8

1. NO

2. Hydrogen sulphide

Question 9

What is the major site of amino acid breakdown?

Answer 9

The liver

Question 10

Name 3 common features of amino acid breakdown.

Answer 10

1. C atoms converted to intermediates of carbohydrate and lipid metabolism
2. Amine group usually removed first
3. N- atoms usually converted to urea

Question 11

What group of enzyme catalyse transamination?

Answer 11

Aminotransferases (transaminases)

Question 12

Which hormone stimulates the production of transaminases in the liver?

Answer 12

Cortisol

Question 13

Which 2 aminotransferases are measure in serum to assess liver function?

Answer 13

1. Alanine aminotransferase (ALT)

2. Aspartate aminotransferase (AST)

Question 14

Give 2 enzymes that catalyse deamination reactions.

Answer 14

1. Glutaminase

2. Glutamate dehydrogenase

Question 15

Why do genetic defects in protein metabolism only usually have clinical consequences when they lead to a defect in protein breakdown?

Answer 15

• Defects in protein synthesis usually overcome by amino acids supplied in the diet
• Whereas the amino acids or its breakdown products may accumulate and become toxic

Question 16

Why do patients with Cushing’s syndrome get striae?

Answer 16

Increased cortisol causes increased protein breakdown, leading to weak skin structure.

Question 17

Which amino acid helps synthesise catecholamines, thyroid hormones and melanin?

Answer 17

Tyrosine

Question 18

Which amino acid is used to make 5-HT?

Answer 18

Tryptophan

Question 19

Which ketoacid is most commonly used to accept the amine group of amino acids during transamination, and what does it produce?

Answer 19

Alpha-ketoglutarate is converted to glutamate.

Question 20

What is the input and output of the urea cycle?

Answer 20

Input= aspartate, glutamate, ammonia

Output= urea

Question 21

Why can referring syndrome occur?

Answer 21

• If raise calorie intake of malnourished patients too quickly
• Their urea cycle enzymes are down-regulated, so get ammonia toxicity if refeed too quickly

Question 22

How would you manage a patient with a genetic defect in the urea cycle?

Answer 22

1. Low protein diet

2. Replace dietary amino acids with ketoacids

Question 23

What is the most common inborn error of amino acid metabolism?

Answer 23

Phenylketonuria (PKU)

Question 24

Which enzyme is deficient in phenylketonuria patients and what is its normal role?

Answer 24

• Phenylalanine hydroxylase

- Converts phenylalanine to tyrosine.

Question 25

What is the treatment for PKU?

Answer 25

• Low phenylalanine diet

- Give dietary tyrosine

Question 26

Why is it important to treat PKU early in babies?

Answer 26

-Untreated, leads to severe intellectual disability

Question 27

How can untreated PKU lead to intellectual disability?

Answer 27

• Excess phenylalanine competes for amino acid transporters in blood brain barrier, so reduced uptake of other amino acids in brain
• Phenylalanine not converted to tyrosine- needed for synthesis of multiple NTs

Question 28

Why would untreated PKU lead to hypopigmentation?

Answer 28

• Patients lack phenylalanine hydroxylase so cannot convert phenylalanine to tyrosine.
• Less tyrosine, so less melanin (gives skin its pigment).

Question 29

Which enzyme is defective in homocystinuria?

Answer 29

Cystathione-beta synthase

Question 30

Which 2 substances accumulate in the blood in homocystinuria?

Answer 30

1. Methionine

2. Homocysteine

Question 31

Which other disease can homocystinuria initially present similarly to?

Answer 31

Marfan’s syndrome

Question 32

Which substance is found in excess in the urine in patients with homocystinuria?

Answer 32

Homocystine (oxidised form of homocysteine)

Question 33

How would you manage a patient with homocystinuria?

Answer 33

1. Low methionine diet (avoid milk, eggs, cheese etc)

2. Give vit B6/12, Betaine and folate supplements to promote conversion of homocysteine to methionine to lower CV risk

Question 34

Why do patients with homocystinuria get neurological symptoms?

Answer 34

• Excess methionine

- Methionine metabolites are toxic to neurones