Metabolic Pathways - 2/25 Seidler

Question 1

What are the major phenylketones?

Answer 1

Phenylpyruvate and phenylacetate

Question 2

What is secondary PKU a result of?

Answer 2

Insufficient BH4 (tetrahydrobiopterin)

Question 3

What are the consequences of excess Phe?

Answer 3

Inhibition of tyrosinase
DEC in serotonin synthesis
DEC in GABA synthesis
Loss of 5-10 IQ units every 10 weeks

Question 4

What labs test for Phe?

Answer 4

Guthrie test - bacterial inhibition assay

Mass spec

Question 5

What are normal plasma [ ]’s of Phe?

PKU?

Answer 5

1 mg/gl (0.06mM)

10-60 mg/dL (0.61-3.62mM)

Question 6

What is maternal PKU?

Causes what?

Answer 6

Phe crosses the placenta

Mental retardation and microcephaly

Question 7

What is alkaptonuria a defect in?

What substrate builds up?

What product is not made?

Answer 7

Homogentisate oxidase

Homogentisate

Malelacetoacetate

Question 8

Clinical Presentation of Alkaptonuria?

Answer 8

Presents in 20-30s 
Discoloration of sclera (ochronosis)
Dark urine
Kidney disease
Osteoarthritis

Question 9

Albinism is defect in what?

Between what?

Answer 9

Tyrosinase

Tyrosine -> dopa

Question 10

clinical presentation of albinism?

Answer 10

Unable to synthesize melanin
Ocular defects
INC risk of basal cell and squamous cell carcinoma

Question 11

Tyrosinemia type I is a defect in what enzyme?

What substrate builds up?

What product is not made?

Answer 11

Fumarylacetoacetate hydrolase

Fumarylacetoacetate

Acetoacetate/Fumarate

Question 12

What is the alternative degradation pathway of tyrosinemia?

Answer 12

Fumarylacetoacetate to succinylacetone

Question 13

Common smell of tyrosinemia?

What kind of problems?

Answer 13

Cabbage-like

Liver failure

Question 14

What enzyme is defective in homocystinuria?

What substrate builds up?

What product is not made?

Answer 14

Cystathionine B-synthase

Homocysteine

Cystathionine

Question 15

What is the alternative degradation pathway in homocystinuria?

Answer 15

Homocysteine thiolactone

Question 16

What Vitamin is needed for conversion of homocysteine to Cystathionine?

Answer 16

Vit B6 (pyridoxine)

Question 17

What vitamins are needed for sufficient synthesis of Methionine?

Answer 17

B6, B12, folic acid

Question 18

Clinical features of homocystinuria?

Answer 18

DVT
Stroke
Atherosclerosis 
Marian-like habits
Retarded
Joint contractures

Question 19

Maple Syrup Urine disease is a result of what defective enzyme?

Answer 19

Alpha-ketoacid decarboxylase

Question 20

Which a.a. Are affected by maple syrup urine disease?

Answer 20

Val
Ile
Leu

Question 21

Symptoms of maple syrup urine disease?

Answer 21

Feeding difficulties 3-4 days after birth, vomiting, lethargic
Progressive neurodegeneration
Abnormal muscle tone
Coma, death

Question 22

What smell does maple syrup urine disease have?

Why?

Answer 22

Burnt sugar

elevated BCAAs and a-ketoacids

Question 23

What enzyme is deficient in galactosemia?

2ndary enzyme?

Third?

Answer 23

Galactose-1-phosphate uridyl transferase

Galactose are

UDP-galactose-4’epiermase

Question 24

What is the alternative pathway if galactose builds up?

Answer 24

Galactitiol

Question 25

What other substrate builds up with galactosemia which has toxic effects?

Answer 25

Galactose-1-phosphate

Question 26

Clinical presentation of galactosemia?

Answer 26

Infants cannot use galactose
They suffer from malnutrition, failure to thrive
Retarded, cataracts
Vomiting, diarrhea, jaundice, hepatomegaly

Question 27

What enzyme is deficient in PKU?

What substrate builds up?
What product does not form?

Answer 27

Phenylalanine hydroxylase

Phenylalanine

Tyrosine