A middle-aged man is brought to the hospital for a neurological examination after displaying uncontrollable movements of his upper limbs. He is diagnosed with a rare genetic disorder affecting dopamine synthesis in brainstem neurons. However, there is some controversy concerning the step in the biosynthesis of dopamine at which this failure takes place. If the failure lies in the immediate precursor stage in the biosynthesis of dopamine, which of the following is the precursor?
d. L-Dihydroxyphenylalanine (L-DOPA)
e. Dopamine β-hydroxylase
The answer is D. (Kandel, pp 282-284. Siegel and Sapru, pp 115-118.) The biosynthesis of catecholamines includes the following steps: tyrosine is converted into L-DOPA by tyrosine hydroxylase; L-DOPA is then decarboxylated by a decarboxylase to form dopamine (and CO2). The conversion of dopamine to norepinephrine comes about by the action of the enzyme dopamine β-hydroxylase. The rate-limiting enzyme in the biosynthesis of serotonin is tryptophan hydroxylase. In this process, tryptophan is converted to 5-hydroxytryptophan by tryptophan hydroxylase and by 5-hydroxytryptophan decarboxylase into serotonin.
If a patient is suffering from a genetic disorder affecting the rate-limiting step in the biosynthesis of dopamine, which of the following is the rate-limiting step?
a. Tryptophan hydroxylase
c. Dopamine β-hydroxylase
e. Choline acetyltransferase
The answer is B. (Kandel, pp 282-284. Siegel and Sapru, pp 115-117.) The rate-limiting step in the biosynthesis of dopamine is tyrosine hydroxylase, which converts tyrosine into L-DOPA. The rate-limiting step in the biosynthesis of serotonin is tryptophan hydroxylase. The enzyme dopamine β-hydroxylase converts dopamine to norepinephrine. Phenylethanolamine-N-methyltransferase is involved in the conversion of norepinephrine to epinephrine. Choline acetyltransferase is involved in the biosynthesis of ACh.
A baby is born with an inherited autosomal recessive trait, causing a delay in development and resulting in the occurrence of seizures and mental retardation. The child is diagnosed with phenylketonuria (PKU). Which of the following is the most likely neurochemical locus of this genetic defect?
c. Tryptophan hydroxylase
e. Phenylalanine (Phe) hydroxylase
The answer is E. (Kandel, pp ...