DISORDERS OF AMINO ACID METABOLISM

Question 1

Describe Hartnups disease

Answer 1

• Hartnups disease is due to the defect in the transport for neutral amino acid such as tryptophan
• Due to the defect of tryptophan in the gastrointestinal tract (GIT) and kidney, the amount of niacin is reduced
• The deficiency of niacin lead to pellagra
• The symptoms of pellagra are 3Ds which are diarrhea, dementia and dermatitis.
• To cure this disease, the patient are given high protein food with the addition of niacin.

Question 2

State the types of PKU

Answer 2

1. Hyperphenylalanimemia type I
2. Hyperphenylalaninemia type II and III
3. Hyperphenylalaninemia type IV and V

Question 3

State what caused each type of PKU defect.

Answer 3

1. Hyperphenylalaninemia type I = phenylalanine hydroxylase (PAH) enzyme
2. Hydrophenylalaninemia type II and III = dihydrobiopterin reductase
3. Hyperphenylalaninemia type IV and V= dihydrobiopterin biosynthesis

Question 4

State the enzyme deficient in phenylketonuria.

Answer 4

1. Defect in phenylalanine hydroxylase (PAH) enzyme for type I
2. Defect in dihydrobiopterin reductase enzyme for type II and type III
3. Defect in dihydrobiopterin biosynthesis for type IV and V

Question 5

Explain the underlying biochemical changes for the clinical manifestation in phenylketonuria (PKU).

Answer 5

• Deficiency in phenylalanine hydroxylase enzyme is due to the mutation gene in the enzyme.
• The function of phenylalanine hydroxylase is to convert phenylalanine to tyrosine in the urine, plasma, and tissues,
• Due to deficiency phenylalanine hydroxylase enzyme in the body, this causes an elevation amount of phenylalanine and deficient amount of tyrosine in the body.
• Hence, phenylalanine undergoes transamination process to produce phenyl lactate and phenyl acetate.
• The high amount of phenyl acetate and phenyl lactate will be excreted out as urine
• The urine produce will be musty, or mousey odour

Question 6

Explain the chemical manifestations in phenylketonuria.

Answer 6

• If phenylketonuria is not treated, it will cause mental retardation when excess phenylalanine enters the CNS.
• In fact, phenylketonuria also cause growth failure.
• This is because, in phenylketonuria, if the phenylalanine cannot be converted, then it cannot synthesis other amino acids such as dopamine and tyrosine.
• the deficiency of dopamine and tyrosine in the body causes the growth to stop.
• Other than that, it also causes the low amount of thyroid hormone produce.
• the low amount of thyroid hormone produce causes the individual to faced low IQ level.
• lastly, phenylketonuria causes hyperpigmentation due to impairment of melanin synthesis

Question 7

State how screening for PKU is done.

Answer 7

1. Southern blotting
2. restriction enzyme digestion
3. DNA sequencing
4. Multiplex ligation probe amplification (MLPA)

Question 8

State other inborn error of amino acid metabolism that causes mental retardation other than PKU

Answer 8

Maple syrup urine disease

Question 9

Describe the biochemical defects in maple syrup urine disease

Answer 9

• Maple syrup urine disease is caused by deficiency of a- keto acid dehydrogenase enzyme
• The function of a-keto acid dehydrogenase is to catalysed the decarboxylation of branched amino acid such as leucine, valine and isoleucine.
• Due to deficiency of a-keto acid dehydrogenase enzyme, the branched amino acid such as leucine is rapidly transported across the blood-brain barrier.
• the accumulation of leucine in the blood causes glutamate to produce and this production causes the formation of inhibitory neurotransmitter GABA to increase, neurological symptoms and brain damage.
• In fact, the accumulation of leucine also can be excreted out through urine
• the urine produced will have burnt sugar or maple syrup odour.

Question 10

State the enzyme defect in sulphur amino acid metabolism below:

1. cystinosis
2. homocystinuria type I
3. homocystinuria type II
4. homocystinuria type III
5. cystathionuria

Answer 10

1. cystinosis = cystine utilisation
2. homocystinuria type I = cystathionine synthase
3. homocystinuria type II = THF reductase
4. homocystinuria type III = n5- methyl THF- homocysteine methyltransferase
5. cystathionuria = cystathionase

Question 11

Briefly describe the biochemical changes in alkaptonuria.

Answer 11

• In alkaptonuria, it is due to the deficiency in homogentisic acid oxidase.
• the deficiency of homogentisic acid oxidase causes the amount of homogentisic acid to accumulate in the blood and tissues
• The accumulation of homogentisic acid causes the urine to be darken in colour.
• in fact, this also can lead to large joint arthritis.
• furthermore, the collagenous tissues and cartilage will shows dark pigmentation due to oxidation of homogentisate which then polymerises and binds to tissues.

Question 12

How to reduce the level of homogentisic acids and the amount of pigments in the body tissues

Answer 12

Practise diet low in PA and tyrosine

Question 13

What is the caused of albinism?

Answer 13

The caused of albinism is due to defect in tyrosine metabolism which lead to deficiency in melanin

Question 14

What is the side effect of deficiency of melanin?

Answer 14

• absence pigment from
  hair, eyes and skin
• vision defects
• high risk of skin cancer