Metabolism IX

Question 1

What cofactors are involved in metabolizing glycine to other substrates?

Answer 1

B6 (p.107)

Question 2

What cofactors are involved in metabolizing gluatmate to other substrates?

Answer 2

B6 (p.107)

Question 3

Describe the pathway of catecholamine synthesis.

Answer 3

1. Phenylalanine –> Tyrosine (via phenylalanine hydroxylase); 2. Tyrosine –> dihydroxyphenylalanine (aka Dopa) (via tyrosine hydroxylase); 3. dopa –> dopamine (via dopa decarboxylase and requiring B6); 4. dopamine –> norepinephrine (via dopamine-b-hydroxylase and requiring vitamin C); 5. Norepinephrine –> epinephrine (via phenylethanolamine N-methyltransferase and requiring SAM) (p.108)

Question 4

What enzyme does carbidopa inhibit?

Answer 4

Dopa decarboxylase, preventing synthesis of dopamine from dopa (p.108)

Question 5

What is the effect of cortisol on norepinephrine?

Answer 5

Induces conversion to epinephrine (p.108)

Question 6

What is the function of SAM?

Answer 6

To add a methyl group to a substrate (p.108)

Question 7

What is the breakdown product of dopamine via MAO and COMT?

Answer 7

HVA (p.108)

Question 8

What is the breakdown product of norepinephrine via MAO and COMT?

Answer 8

VMA (p.108)

Question 9

What is the breakdown product of epinephrine via MAO and COMT?

Answer 9

Metanephrine (p.108)

Question 10

What is the pathology associated with phenylketonuria?

Answer 10

Caused by decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU). Increased phenylalanine causes excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate) in urine and makes tyrosine an essential amino acid (p.108)

Question 11

What is the pattern of inheritance associated with phenylketonuria?

Answer 11

An autosomal recessive condition with incidence about 1:10,000. It is screened for 2-3 days after birth (because it is nrmal at birth due to maternal enzyme during fetal life) (p.108)

Question 12

What are the symptoms of phenylketonuria?

Answer 12

Mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor (p.108)

Question 13

What is the treatment for phenylketonuria?

Answer 13

Decrease phenylalanine in diet (contained in aspartame) and increase tyrosine in diet (p.108)

Question 14

What is maternal PKU?

Answer 14

Lack of proper dietary therapy during pregnancy causes an infact to have microcephaly, mental retardation, growth retardation, and congenital heart defects (p.108)

Question 15

What is alkaptonuria (ochronosis)?

Answer 15

A congenital deficiency of homogentistic acid oxidase in the degredative pathyway of tyrosine to fumarate. It is a benign disease (p.108)

Question 16

What is the inheritance pattern associated with alkaptonuria?

Answer 16

Autosomal recessive (p.108)

Question 17

What are the clinical findings in a patient with alkaptonuria?

Answer 17

Dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. May have debilitating arthralgias as homogentisic acid is toxic to cartilage (p.108)

Question 18

What is the pathology associated with albinism?

Answer 18

A congenital deficiency of either tyrosinase (inability to synthesize melanin from tyrosine) or due to defective tyrosine transporters which decrease the amount of tyrosine and thus melanin. It can also result from a lack of migration of neural crest cells. (p.108)

Question 19

What is the inheritance pattern associated with albinism?

Answer 19

Can be autosomal recessive but inheritance is variable due to locus heterogeneity (p.108)

Question 20

What is the pattern of inheritance of occular albinism?

Answer 20

X-linked recessive (p.108)

Question 21

Describe the three pathologies that may lead to homocystinuria.

Answer 21

1.) Cystathionine synthase deficiency; 2.) Decreased affinity of cystathionine synthase for pyridoxal phosphate; 3.) Homocysteine methyltransferase (requires B12) deficiency (p.109)

Question 22

What is the pattern of inheritance in homocystinuria?

Answer 22

All three types are autosomal recessive (p.109)

Question 23

How do you treat homocystinuria associated with a cystathionine synthase deficiency?

Answer 23

Decrease methionine and increase cysteine, Vitamin B12, and folate in the diet (p.109)

Question 24

How do you treat homocystinuria associated with a decreased affinity of cystathionine synthase for pyridoxal phosphate?

Answer 24

Increase vitamin B6 in diet (p.109)

Question 25

Describe the clinical and lab findings in a patient with homocystinuria.

Answer 25

All forms of homocystinuria result in excess homocysteine amd makes cysteine essential. Findings include increased homocysteine in the urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downwards and inwards), and atherosclerosis (stroke and MI) (p.109)