Block 3 Lipid Synth & Storage

1. A 42-year-old man presents with a chief complaint of intermittent claudication during exercise. His family history is significant for the presence of cardiovascular disease on his father's side, but not on his mother's side. Physical exam reveals xanthelasmas and bilateral tendon xanthomas. A plasma lipid profile reveals a cholesterol level of 340 mg/dL, with a high LDL/HDL ratio. He is given instructions for dietary modifications and a prescription for Zocor (simvastatin). The anticholesterolemic action of simvastatin is based on its effectiveness as a competitive inhibitor of the rate-limiting enzyme in cholesterol biosynthesis. The reaction product normally produced by this enzyme is

Squalene

Methylmalonate

Lanosterol

Mevalonate

Acetoacetate

Must know that mevalonate precedes squalene and lanosterol in the pathway,
and that methylmalonate and acetoacetate are not associated with cholesterolgenesis.

Explanation

Must know that mevalonate precedes squalene and lanosterol in the pathway,
and that methylmalonate and acetoacetate are not associated with cholesterolgenesis.

2. A patient with a history of recurring attacks of pancreatitis, eruptive xanthomas, and increased plasma triglyceride levels (2000 mg/dL) associated with chylomicrons, most likely has a deficiency in

Lipoprotein lipase

LDLreceptors

HMG-CoA reductase

ApoB-48

ApoB-lOOreceptor

These are the clinical features of lipoprotein lipase deficiency (TypeI lipoproteinemia).
LDLreceptor defects would result in elevated LDLs.HMG-CoA reductase and
ApoB-lOOhave no direct relationship to chylomicrons. ApoB-48 deficiencywould result
in decreased production of chylomicrons.

Explanation

These are the clinical features of lipoprotein lipase deficiency (TypeI lipoproteinemia).
LDLreceptor defects would result in elevated LDLs.HMG-CoA reductase and
ApoB-lOOhave no direct relationship to chylomicrons. ApoB-48 deficiencywould result
in decreased production of chylomicrons.

3. Uncontrolled phagocytosis of oxidized LDL particles is a major stimulus for the development of foam cells and fatty streaks in the vascular sub endothelium. This process may be inhibited by increased dietary intake of

Vitamin E

Vitamin B6

Vitamin D

Vitamin B12

Vitamin K

Only vitamin E is an antioxidant

Explanation

Only vitamin E is an antioxidant

4. Abetalipoproteinemia is a genetic disorder characterized by malabsorption of dietary lipid, steatorrhea (fatty stools), accumulation of intestinal triglyceride, and hypolipoproteinemia. A deficiency in the production of which apoprotein would most likely account for this clinical presentation?

ApoB-lOO

ApoB-48

ApoC-II

ApoA-I

ApoE

Apo B-48is required for intestinal absorption of dietary fat in the form of chylomicrons.
Apo B-lOOformation is also impaired in these patients, but this would not
explain the clinical symptoms described.

Explanation

Apo B-48is required for intestinal absorption of dietary fat in the form of chylomicrons.
Apo B-lOOformation is also impaired in these patients, but this would not
explain the clinical symptoms described.

5. What is the most positive activator of the process shown below? 8 acetylCoA + n ATP + 14NADPH -7 palmitate + 8 CoASH+ nADP + nPi + 14NADP

Acetyl CoA

Citrate

Malonyl CoA

Malate

Oxaloacetate

Citrate is a potent activator of acetylCoA carboxylase for fatty acid synthesis.

Explanation

Citrate is a potent activator of acetylCoA carboxylase for fatty acid synthesis.

6. When adipose tissue stores triglyceride arriving from the liver or intestine, glycolysis must also occur in the adipocyte. Which of the following products or intermediates of glycolysis is required for fat storage?

Glycerol

Glucose 6-phosphate

Pyruvate

Acetyl CoA

Dihydroxyacetone phosphate

To reform triglycerides trom the incoming fatty acids, glycerol 3-P must be
available.The adipose can produce this only from DHAP in glycolysis.

Explanation

To reform triglycerides trom the incoming fatty acids, glycerol 3-P must be
available.The adipose can produce this only from DHAP in glycolysis.

7. Abetalipoproteinemia is a genetic disorder characterized by malabsorption of dietary lipid, steatorrhea (fatty stools), accumulation of intestinal triglyceride, and hypolipoproteinemia Patients with abetalipoproteinemia exhibit membrane abnormalities in their erythrocytes with production of acanthocytes (thorny-appearing cells). This unusual red cell morphology would most likely result from malabsorption of

Palmitic acid

Ascorbic acid

Arachidonic acid

Folic acid

Linoleic acid

The genetic defect would result in malabsorption of the 3 fatty acids listed, but
only linoleate is strictly essential in the diet. Absorption of water-soluble ascorbate and
folate would not be significantly affected.

Explanation

The genetic defect would result in malabsorption of the 3 fatty acids listed, but
only linoleate is strictly essential in the diet. Absorption of water-soluble ascorbate and
folate would not be significantly affected.

8. A 42-year-old man presents with a chief complaint of intermittent claudication during exercise. His family history is significant for the presence of cardiovascular disease on his father's side, but not on his mother's side. Physical exam reveals xanthelasmas and bilateral tendon xanthomas. A plasma lipid profile reveals a cholesterol level of 340 mg/dL, with a high LDL/HDL ratio. He is given instructions for dietary modifications and a prescription for Zocor (simvastatin). From a Lineweaver-Burk plot, the Km and Vmaxof this rate-limiting enzyme were calculated to be 4 X 10^-3 M and 8 X 10² mmol/h, respectively. If the above experiment is repeated in the presence of simvastatin, which of the following values would be obtained? Km (M) V max (mmolJh)

With a competitive inhibitor, there will be an increase in Km with no change in
Vmax'Option A would be for a noncompetitive inhibitor (V max decreased, Km unaltered).

Explanation

With a competitive inhibitor, there will be an increase in Km with no change in
Vmax'Option A would be for a noncompetitive inhibitor (V max decreased, Km unaltered).

9. A 42-year-old man presents with a chief complaint of intermittent claudication during exercise. His family history is significant for the presence of cardiovascular disease on his father's side, but not on his mother's side. Physical exam reveals xanthelasmas and bilateral tendon xanthomas. A plasma lipid profile reveals a cholesterol level of 340 mg/dL, with a high LDL/HDL ratio. He is given instructions for dietary modifications and a prescription for Zocor (simvastatin). The clinical findings noted in this patient are most likely caused by deficient production of

Lethicin cholesterol acyltransferase

ApoB-lOO receptors

Fatty acyl-CoA synthetase

VLDL from LDL

Cholesterol ester transfer protein

The findings are indicative of heterozygous Type lla familial hypercholesterolemia,
an autosomal dominant disease. Deficient CETP,LCATor fatty acid CoA synthetase
would not elevate LDLcholesterol.VLDLare not produced from LDL.

Explanation

The findings are indicative of heterozygous Type lla familial hypercholesterolemia,
an autosomal dominant disease. Deficient CETP,LCATor fatty acid CoA synthetase
would not elevate LDLcholesterol.VLDLare not produced from LDL.