Metabolism X

Question 1

What reaction is catalyzed by Homocysteine methyltransferase and what cofactor is required?

Answer 1

Homocysteine –> methionine (requires B12) (p.109)

Question 2

How is homocysteine converted to cysteine?

Answer 2

Homocysteine is converted to cystathionine via cystathionine syntase. Serine and B6 are required for this reaction. Cystathionine is then converted to cysteine (p.109)

Question 3

Describe the pathology associated with cystinuria?

Answer 3

A hereditary defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in the PCT of the kidneys (p.109)

Question 4

What are the symptoms of cystinuria?

Answer 4

Excess cysteine in the urine which may cause precipitation of hexagonal crystals and renal staghorn caliculi (p.109)

Question 5

How is cystinuria inherited?

Answer 5

Autosomal recessive condition. It is relatively common (1:7000) (p.109)

Question 6

How is cystinuria treated?

Answer 6

Good hydration and urinary alkalization (p.109)

Question 7

Describe the pathology associated with maple syrup urine disease?

Answer 7

Blocked degradation of branched amino acids (Ile, Leu, Val) due to decreased a-ketoacid dehydrogenase (B1) causing increased a-ketoacids in the blood (especially Leucine) (p.109)

Question 8

What are the symptoms of maple syrup urine disease?

Answer 8

Severe CNS defects, mental retardation, death. Urine smells like maple syrup (p.109)

Question 9

How is maple syrup urine disease inherited?

Answer 9

Autosomal recessive (p.109)

Question 10

What is Hartnup disease?

Answer 10

A disorder characterized by defective neutral amino acid transporters on renal and intestinal epithelial cells (p.109)

Question 11

What is the clinical manifestation of Hartnup disease?

Answer 11

Tryptophan excretion in urine and decreased tryptophan absorption in the gut. It leads to pellagra (p.109)

Question 12

How is Hartnup disease inherited?

Answer 12

Autosomal recessive (p.109)

Question 13

What condition can Hartnup disease lead to?

Answer 13

Pellagra (p.109)

Question 14

How is glycogenolysis coordinated with muscle activity?

Answer 14

Calcium/ Calmodulin in muscle activates phosphorylase kinase so that glyconeolysis is coordinated with muscle activity (p.110)

Question 15

How do glucagon (from the liver) and epinephrine (from the liver and muscle) regulate glycogenolysis?

Answer 15

By activating a cascade which increases cAMP, acting on protein kinase A which induces glycogenolysis (p.110)

Question 16

How does insulin affect glycogenolysis?

Answer 16

It inactivates glycogen phosphorylase and glycogen phosphorylase kinase via protein phosphatase which decreases glycogenolysis (p.110)

Question 17

How do glycogen branches differ from glycogen linkages?

Answer 17

Glycogen branches have a(1,6) bonds; linkages have 1(1,4 bonds) (p.110)

Question 18

How does skeletal muscle utilize glycogen?

Answer 18

Glycogen undergoes glycogenolysis to become glucose-1-phosphate. Glucose-1-phosphate becomes glucose-6-phosphate which is rapidly metabolized during exercise (p.110)

Question 19

How do hepatocytes utilize glycogen?

Answer 19

Glycogen is stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels (p.110)

Question 20

Outline the process of glycogen synthesis.

Answer 20

Glucose-6-phosphate Glucose-1-phosphate. Glucose-1-phosphate –> UDP glucose via UDP glucose pyrophosphorylase. UDP glucose –> storage form of glycogen via glycogen synthase. Storage form attains branches and linkages via branching enzyme, glycogen phosphorylase, and debranching enzyme (p.110)

Question 21

How many glycogen storage diseases are there and what conditions are characteristic of all glycogen storage diseases?

Answer 21

12 types, all which result in abnormal glycogen metabolism and an accumulation of glycogen within cells (p.111)

Question 22

Describe the findings associated with Von Gierke’s disease (type I).

Answer 22

Glycogen storage disease; severe fasting hypoglycemia, increased glycogen in the liver, increased blood lactate, hepatomeagly (p.111)

Question 23

Describe the findings associated with Pompe’s disease (type II).

Answer 23

Glycogen storage disease; Cardiomeagly and systemic findings (heart, liver, muscle) leading to early death (p.111)

Question 24

Describe the findings associated with Cori’s disease (type III)

Answer 24

Glycogen storage disease that is a milder form of von Gierke’s disease with normal blood lactate levels. Gluconeogenesis is intact (p.111)

Question 25

Describe the findings associated with McArdle’s disease (type V).

Answer 25

Glycogen storage disease; increased glycogen in muscle that can not be broken down which leads to painful cramps and myoglobinuria with strenuous exercise (p.111)

Question 26

What enzyme is deficient in von Gierke’s disease?

Answer 26

Glucose-6-phosphatase (p.111)