Lipoprotein/Cholesterol Metabolism

FAMILIAL HYPERCHOLESTEROLEMIA (Lipoprotein/Cholesterol Metabolism)

Brown and Goldstein studied LDL metabolism in cells from patients with a common metabolic inherited disorder called familial hypercholesterolemia (FH). People homozygous for this mutation have a6- to l0-fold elevation of LDL levels, are born with detectable atherosclerosis, and usually do not survive childhood without a myocardial infarction. Heterozygotes have two- to fourfold elevations in […]

HOW DO STEROLS REGULATE GENE EXPRESSION? (Lipoprotein/Cholesterol Metabolism)

Cholesterol regulates its own formation by inhibiting the transcription of several genes in the cholesterol pathway, most notably HMG-CoA synthase and HMG-CoA reduc-tase. For many years it was also known that polyunsatu-rated fats decrease the level of cholesterol synthesis. Now we know how these regulatory events occur. The transcription of the cholesterol-regulated genes is regulated […]

OTHER LIPOPROTEIN RECEPTORS (Lipoprotein/Cholesterol Metabolism)

A. LRP/a2-Macroglobulin Receptor The lipoprotein receptor-related protein (LRP)/a2-macroglobulin receptor (LRP) has a mass about five times larger than the LDL receptor. It contains many of the same structural domains as the LDL receptor, including a cysteine-rich repeat domain that binds to lipoproteins. In vitro studies have shown that the LRP does not bind to apo-B100, […]

HDL AND "REVERSE CHOLESTEROL TRANSPORT" (Lipoprotein/Cholesterol Metabolism)

Epidemiological studies show a strong inverse relationship between HDL levels (HDL cholesterol or apo-A1) and risk of CHD. Even a small increase in HDL is significantly correlated with a reduction in the risk of premature heart disease. Unlike VLDL and chylomicrons, HDL is formed from its protein and lipid components in the bloodstream and interstitial […]

TANGIER DISEASE AND FAMILIAL HYPOALPHALIPOPROTEINEMIA (Lipoprotein/Cholesterol Metabolism)

Tangier disease is a rare recessive disorder in which patients have almost no HDL. Cholesterol ester accumulates in macrophages and macrophage-rich tissues like spleen and liver. Familial hypoalphalipoproteinemia (FHA) is a very common dominant disorder in which people have low HDL (typically <30 mg/dl) and suffer from premature heart disease even without an elevation in […]

Lp(a) AND apo(a) (Lipoprotein/Cholesterol Metabolism)

Apo(a) is a protein found covalently linked to apo-B100 in some LDL particles. Those LDL particles to which apo(a) is attached are called lipoprotein(a) or Lp(a). Plasma levels of Lp(a) correlate with increased cardiovascular disease risk in most populations, but not in African-Americans. The level of Lp(a) appears to be entirely genetically determined. The Lp(a) […]

COMMON ISOFORMS OF APOLIPOPROTEIN E (apoE) (Lipoprotein/Cholesterol Metabolism)

Apo-E occurs in three common isoforms, apo-E2, apo-E3, and apo-E4. They differ at amino acids 112 and 158 (Table VII). In apo-E4, both of these amino acids are argi-nine. In apo-E2, both amino acids are cysteine, and apo-E3 has Cys-112 and Arg-158. The presence of cysteine at amino acid 158 virtually abolishes the LDL receptor-binding […]

Apo-E AND ALZHEIMER’S DISEASE (Lipoprotein/Cholesterol Metabolism)

Epidemiological studies have revealed a correlation between the apo-E4 allele and risk of developing Alzheimer’s disease. About 80% of familial and 64% of sporadic Alzheimer’s disease late-onset cases have at least one apo-E4 allele, compared to 31% of control subjects. The apparent risk is dose dependent. In one study, 91% of E4/E4 homozygous individuals from […]

FAMILIAL COMBINED HYPERLIPIDEMIA AND HYPERTRIGLYCERIDEMIA (Lipoprotein/Cholesterol Metabolism)

A very common disorder frequently associated with elevated VLDL and LDL or elevated VLDL only is termed familial combined hyperlipidemia (FCHL) (Table VIII). In order to make a diagnosis, the family of the patient must be screened. Some family members will display increases in VLDL, others in LDL, and some in both VLDL and TABLE […]

TREATMENT OF LIPOPROTEIN DISORDERS

Treatment of lipoprotein disorders is primarily aimed at achieving relatively low VLDL and LDL levels and relatively high HDL levels. Since obesity and insulin resistance are often associated with elevated VLDL, weight loss and exercise are often effective in reducing VLDL. Exercise has an insulin-sensitizing effect on muscle; thus regular exercise can have long-term effects […]

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