Metabolism Of Membrane Lipids.

1. One in 30 Ashkenazi Jews carries a mutation for Tay-Sachs disease in the heterozygous state. The heterozygotes can be identified by measuring one of the following enzymes in cultured leucocytes:

Glucocerebrosidase

Hexosaminidase A

Iduronate sulfatase

Ceramidase

B-galactosidase

Hexosaminidase A removes N-acetyl-galactosamine from ganglioside GM2.

Explanation

Hexosaminidase A removes N-acetyl-galactosamine from ganglioside GM2.

2. Statins are the most important type of cholesterol-lowering drug, and they lower specifically LDL rather than HDL cholesterol. How do the statins lower LDL cholesterol?

By reducing the synthesis of apo B-100, the major structural protein of VLDL and LDL

By stimulating the conversion of excess cholesterol to bile acids in the liver, thereby depleting cholesterol for LDL synthesis

By stimulating the transfer of cholesterol esters from VLDL and LDL to HDL

By inhibiting HMG-CoA reductase, thereby preventing cholesterol synthesis and forcing the cells to obtain their cholesterol from LDL

When the cells cannot make their own cholesterol, they have to snatch it from circulating LDL. To that end, they increase their synthesis of LDL receptors.

Explanation

When the cells cannot make their own cholesterol, they have to snatch it from circulating LDL. To that end, they increase their synthesis of LDL receptors.

3. You culture fibroblasts from a patient in the laboratory. In order to up-regulate the low-density lipoprotein (LDL) receptors in these cells you should:

Add cholesterol esters to the medium

Add excess LDL to the medium

Inhibit HMG-CoA reductase

Inhibit the activity of acyl-CoA-cholesterol-acyl transferase (ACAT)

Add cholestyramine

By inhibiting cholesterol synthesis, cellular free cholesterol is reduced and LDL receptors are upregulated.

Explanation

By inhibiting cholesterol synthesis, cellular free cholesterol is reduced and LDL receptors are upregulated.

4. A 5-year-old girl is presented with hepatosplenomegaly, abnormal bleeding, defects in long bone development, and neurological dysfunction. A liver biopsy reveals an accumulation of glucocerebroside. These symptoms indicate the child is suffering from:

Fabry's disease

Niemann-Pick disease

Krabbe's disease

Gaucher's disease

Hurler syndrome

Gaucher’s disease, which comes in different degrees of severity, is caused by glucocerebrosidase deficiency.

Explanation

Gaucher’s disease, which comes in different degrees of severity, is caused by glucocerebrosidase deficiency.

5. The alleles in the ABO blood group system code for:

Integral membrane proteins

Glycosyl transferases

Peripheral membrane proteins

Cytoskeletal proteins

Phosphoglyceride-synthesizing enzymes

The ABO antigens are oligosaccharide chains of membrane lipids. These oligosaccharides are synthesized by glycosyl transferases in the ER and Golgi.

Explanation

The ABO antigens are oligosaccharide chains of membrane lipids. These oligosaccharides are synthesized by glycosyl transferases in the ER and Golgi.

6. 3-hydroxy, 3-methylglutaryl-CoA (HMG-CoA) is not only the substrate for the rate-limiting enzyme of cholesterol synthesis, but also an intermediate in the synthesis of:

Heme

Purines

Pyrimidines

Ketone bodies

Glutathione

HMG-CoA in the cytoplasm is a precursor for cholesterol. In the mitochondria it forms ketones.

Explanation

HMG-CoA in the cytoplasm is a precursor for cholesterol. In the mitochondria it forms ketones.

7. A pregnant woman mentions that 2 years ago, her first child died 2 weeks after birth because the newborn's "lungs were immature" at birth. Since you are planning a C-section, you want to determine first whether there is a risk of respiratory problems for her current baby. Which of the following results from an analysis of her amniotic fluid would indicate a high risk?

A low ratio of free cholesterol/cholesterol esters

An elevated glucose level

A low lecithin/shingomyelin ratio

An elevated level of phosphatidylglycerol

A reduced level of platelet-activating factor

“Lecithin” includes dipalmitoyl-phosphatidylcholine, the major component of lung surfactant. Sphingomyelin is assessed to control for the overall lipid level.

Explanation

“Lecithin” includes dipalmitoyl-phosphatidylcholine, the major component of lung surfactant. Sphingomyelin is assessed to control for the overall lipid level.

8. Hypercholesterolemic patients taking HMG-CoA reductase inhibitors (statins) produce less cholesterol from endogenous synthesis. Lower intracellular cholesterol levels induce which of the following regulatory changes?

Enhanced VLDL formation in the liver

Down-regulation of HMG-CoA reductase

Higher lipoprotein lipase (LPL) activity

Higher plasma chylomicron concentration

An increased number of LDL receptors

Cells acquire cholesterol according to their needs. If they cannot make it themselves, they have to get it from LDL. They do this by making more LDL receptors.

Explanation

Cells acquire cholesterol according to their needs. If they cannot make it themselves, they have to get it from LDL. They do this by making more LDL receptors.

9. Excess cholesterol needs to be transported to the liver because it cannot be metabolized in most extrahepatic tissues. This 'reverse' transport of cholesterol requires a lipoprotein that is not required for other routes of cholesterol transport. This lipoprotein is:

IDL

LDL

HDL

VLDL

Lipoprotein(a)

HDL picks up free cholesterol from cells.

Explanation

HDL picks up free cholesterol from cells.

10. Cholestyramine can be used for the treatment of hypercholesterolemia, either alone or in combination with a statin. Which enzyme is most immediately affected by cholestyramine tratment?

Cholesterol ester transfer protein

Acyl-CoA-cholesterol acyltransferase (ACAT)

7a-hydroxylase

HMG-CoA reductase

Lecithin-cholesterol acyltransferase (LCAT)

Cholestyramine is a non-absorbed ion exchanger that binds bile acids in the small intestine, thus interrupting their enterohepatic circulation. 7a-hydroxylase is disinhibited by the lack of bile acids, and converts excess cholesterol to bile acids.

Explanation

Cholestyramine is a non-absorbed ion exchanger that binds bile acids in the small intestine, thus interrupting their enterohepatic circulation. 7a-hydroxylase is disinhibited by the lack of bile acids, and converts excess cholesterol to bile acids.

11. A 33-year-old man is found to have tendon xanthomas. When questioned about his lifestyle he says that he exercises regularly, eats balanced meals and is not in any physical distress. A blood analysis reveals plasma total cholesterol of 350 mg/dL and triglycerides of 70 mg/dL. He is treated with cholestyramine and a statin and sent for further analysis. His hyperlipidemia is best classified as:

Type I

Type V

Type III

Type IV

Type IIa

This looks like familial hypercholesterolemia.

Explanation

This looks like familial hypercholesterolemia.

12. On physical examination you notice that a patient has tendon xanthomas. A blood analysis reveals a total cholesterol level of 350 mg/dL, which is due mainly to raised levels of LDL, and normal levels of triglyceride. What other investigation would be helpful in this patient?

Look for eruptive xanthomas

Do a VLDL analysis

Isolate the patient's lymphocytes and look for the number of LDL receptors

Check for hyperthyroidism

Do a fasting blood glucose

This looks like familial hypercholesterolemia. In that case you expect a reduction of functional LDL receptors to 50% of normal.

Explanation

This looks like familial hypercholesterolemia. In that case you expect a reduction of functional LDL receptors to 50% of normal.

13. Routine blood studies on an infant show turbid plasma with markedly elevated levels of triacylglycerol. A sample of plasma that has been left in the refrigerator overnight has cream-colored material floating on top. The underlying plasma is clear. Which type of hyperlipoproteinemia is most likely present in this infant?

Type I

Type III

Type IIb

Type IIa

Type IV

Chylomicrons but not VLDL rise to the surface on prolonged standing.

Explanation

Chylomicrons but not VLDL rise to the surface on prolonged standing.

14. A 5-year-old boy develops severe stomach pain after eating a big piece of fatty cheesecake. Serum amylase is found to be mildly elevated. The plasma triglyceride level is 1200 mg/dL, and the total cholesterol is 220 mg/dL. The parents mention that the child does not like fatty foods at all, but this was the first time he tasted cheesecake. Which apolipoprotein might be deficient in this patient to account for his fat intolerance?

A-I

C-II

B-100

C-III

E

The boy has type I hyperlipoproteinemia. Some cases are caused by a deficiency of apoC-II, which is a required activator of lipoprotein lipase. Conditioned taste aversions are common in all metabolic diseases that lead to sickness after eating certain foods.

Explanation

The boy has type I hyperlipoproteinemia. Some cases are caused by a deficiency of apoC-II, which is a required activator of lipoprotein lipase. Conditioned taste aversions are common in all metabolic diseases that lead to sickness after eating certain foods.