Lipid disorders

Published on 02/03/2015 by admin

Filed under Endocrinology, Diabetes and Metabolism

Last modified 02/03/2015

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Lipid disorders

1. What are the major lipids in the bloodstream?

2. What are lipoproteins?

3. What are the major lipoproteins in the bloodstream?

Chylomicrons, very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) are the major circulating lipoproteins. Their functions are as follows:

Chylomicrons Transport exogenous TGs from the gut to adipose tissue and muscle
VLDLs Transport endogenous TGs from the liver to adipose tissue and muscle
LDLs Transport cholesterol from the liver to peripheral tissues
HDLs Transport cholesterol from peripheral tissues to the liver

4. What are the apolipoproteins?

Apolipoproteins are located on the surfaces of the lipoproteins. They function as ligands for binding to lipoprotein receptors and as cofactors for metabolic enzymes. Their functions are as follows:

Apolipoprotein A Ligand for peripheral HDL receptors
Apolipoprotein B Ligand for peripheral LDL receptors
Apolipoprotein E Ligand for hepatic receptors for remnant particles
Apolipoprotein C-II Cofactor for lipoprotein lipase (LPL)

5. Name other enzymes and transport proteins that are important in lipoprotein metabolism.

See Table 6-1 and Figure 6-1.

TABLE 6-1.


Hydroxy-3-methyl-glutaryl-coenzyme A reductase The rate-limiting enzyme in hepatic cholesterol synthesis
Lipoprotein lipase Removes TGs from chylomicrons and VLDLs in adipose tissue, leaving remnant particles
Hepatic lipase Removes additional TGs from remnant particles in the liver, converting them into LDLs
Lecithin cholesterol acyl transferase Esterifies cholesterol molecules on the surface of HDLs, drawing them into the HDL core
Cholesterol ester transfer protein Shuttles esterified cholesterol back and forth between HDLs and LDLs

HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglyceride; VLDL, very-low-density lipoprotein.

6. Explain the function and metabolism of TGs.

7. Describe the function and metabolism of LDL.

8. What is the function of HDL?

HDL removes excess cholesterol from cells by two mechanisms. Nascent pre-βHDL is made in the liver and intestine. Surface Apo A1 on pre-βHDL acquires FC through the adenosine triphosphate (ATP)–binding cassette (ABC) transporter-A1 (ABCA1) on arterial wall macrophages. Plasma lecithin cholesterol acyl transferase (LCAT) then esterifies the FC to cholesterol ester (CE). In addition, HDL accepts additional FC from arterial macrophages through the ABCG1 transporter and the scavenger receptor, class B, type 1 (SR-B1) receptor. Cholesterol ester transfer protein (CETP) transfers some CE back to LDL particles, and the mature HDL transports the remaining CE to the liver, where transfer occurs through hepatic SR-B1 receptors. In addition to performing reverse cholesterol transport, HDL reduces LDL oxidation, inhibits vascular inflammation, and improves endothelial function. All of these functions make HDL a potent antiatherogenic lipoprotein.

9. Describe the pathogenesis of the atherosclerotic plaque and arterial thrombosis.

10. Are elevated serum TG values harmful?

11. What is metabolic syndrome?

12. What is lipoprotein(a) [Lp(a)]?

13. What are the primary dyslipidemias?

Primary dyslipidemias are inherited disorders of lipoprotein metabolism. The major primary dyslipidemias and their lipid phenotypes are as follows:

Familial hypercholesterolemia (FH) ↑↑Cholesterol
Polygenic hypercholesterolemia ↑Cholesterol
Familial combined hyperlipidemia (FCH) ↑Cholesterol and ↑TGs
Familial dysbetalipoproteinemia (FDL) ↑Cholesterol and ↑TGs
Familial hypertriglyceridemia (FHT) ↑TGs
Familial hyperchylomicronemia (FHC) ↑↑TGs

↑, elevated; ↑↑, extremely elevated.

14. What is familial hypercholesterolemia?

FH is an inherited disease characterized by extreme elevations of serum cholesterol but normal serum TG levels. The disorder has a population frequency of 1:500 for heterozygotes, who generally have serum cholesterol levels of 300 to 800 mg/dL, and 1:1,000,000 for homozygotes, who have serum cholesterol levels of 600 to 1000 mg/dL. Most patients have genetic mutations resulting in deficient or dysfunctional LDL receptors (LDLRs). Other less common monogenic hypercholesterolemic disorders include apoprotein B mutations that produce a defective apo B that cannot bind to LDLR, proprotein convertase subtilisin–like kexin type 9 (PCSK9) mutations that cause accelerated LDLR degradation, LDLR adaptor protein-1 (LDLRAP1) mutations that prevent normal clustering of LDLR in cell surface clathrin-coated pits, and ATP-binding cassette G5 or G8 (ABCG5/8) mutations that cause abnormal cellular transport of cholesterol and plant sterols (sitosterolemia). These disorders are characterized by premature coronary artery disease (CAD), often before age 20 in homozygous FH, and tendon xanthomas.

15. What is familial combined hyperlipidemia?

16. What is familial dysbetalipoproteinemia?

17. What is polygenic hypercholesterolemia?

18. What are familial hypertriglyceridemia and familial hyperchylomicronemia?

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