Lipids and Lipoproteins: Biochemistry, Metabolism, and Clinical Significance

What are lipids?

Lipids are organic compounds that are soluble in organic solvents and nearly insoluble in water, primarily consisting of esters of fatty acids.

List the major types of lipids.

Cholesterol, triglycerides, phospholipids, and glycolipids.

What is the primary role of lipids in the body?

They serve as a rich source of energy, store calories, act as hormones, and are structural components of cell membranes.

What are fatty acids?

Linear chains of carbon-hydrogen bonds terminating in a carboxyl group.

What are triglycerides composed of?

Three fatty acid molecules attached to one molecule of glycerol by ester bonds.

Describe phospholipids.

Similar to triglycerides but contain only two esterified fatty acids and a hydrophilic head group.

What is cholesterol?

An unsaturated steroid alcohol with four fused rings and a single side chain tail, synthesized primarily by animals.

How many carbon atoms does cholesterol contain?

Cholesterol contains 27 carbon atoms.

What is the difference between exogenous and endogenous cholesterol?

Exogenous cholesterol is absorbed from the diet, while endogenous cholesterol is produced by the liver.

What are the types of fatty acids?

Saturated, monounsaturated, and polyunsaturated fatty acids.

What are glycerol esters?

Common alcohols in human metabolism, consisting of glycerol, a 3-carbon molecule with three hydroxyl groups.

What are lipoproteins?

Complex micellar structures that transport lipids, consisting of proteins, polar lipids, and neutral lipids.

List the five categories of lipoproteins.

Chylomicrons, Very-low-density lipoproteins (VLDL), Intermediate-density lipoproteins (IDL), Low-density lipoproteins (LDL), and High-density lipoproteins (HDL).

What are apolipoproteins?

Proteins integral to lipoprotein molecules, classified into five major categories: Apo A, B, C, D, and E.

What is the structure of chylomicrons?

Chylomicrons are the largest and least dense lipoproteins, produced by the intestine to deliver dietary lipids.

What is the role of VLDL?

VLDL is produced by the liver and serves as a major carrier of endogenous triglycerides.

How are LDL particles formed?

LDL particles form from the lipolysis of VLDL and are taken up by cells via LDL receptors.

What characterizes HDL?

HDL is the smallest and most dense lipoprotein, synthesized by the liver and intestine, capable of removing excess cholesterol from peripheral cells.

What is Lipoprotein X?

An abnormal form of LDL associated with bile lipids and cholestasis, which can escape into systemic circulation.

What are the four pathways of lipoprotein metabolism?

Lipid absorption, exogenous pathway, endogenous pathway, and reverse cholesterol transport.

Describe the process of lipid absorption.

Dietary lipids are converted to amphipathic lipids that form micelles in the intestinal lumen, which are then absorbed by intestinal mucosal cells.

What is the function of chylomicrons?

Chylomicrons transport dietary or exogenous fat, primarily triglycerides, from the intestines to the liver and peripheral cells.

What are the primary apolipoproteins found in chylomicrons?

A-I, A-II, and B-48

What percentage of chylomicrons is made up of triglycerides?

84%

What is the role of Apo A-1 in the exogenous pathway?

It activates LCAT (Lecithin-Cholesterol acyltransferase) which shifts esterified free cholesterol to the core.

What is the function of Lipoprotein Lipase (LPL) in the exogenous pathway?

C-II activates LPL on the surface of endothelial cells, facilitating the hydrolysis of triglycerides.

What happens to chylomicron remnants in the body?

They are engulfed and catabolized by hepatic cells to synthesize VLDLs, form bile acids, or be stored as cholesteryl esters.

What is the primary function of chylomicrons?

To transport dietary triglycerides from the intestine to hepatic or peripheral cells.

What is the origin of very-low-density lipoproteins (VLDL)?

VLDL originates in the liver from chylomicron remnants and endogenous triglycerides.

What activates LPL in the endogenous pathway?

C-II activates LPL on capillary cell walls and hepatic cells.

What is the principal lipoprotein carrier of cholesterol in plasma?

Low-density lipoproteins (LDL)

How is excess free cholesterol managed in the body?

LDL receptors are decreased on cells with excess cholesterol, and synthesis of endogenous cholesterol is inhibited.

What is the major risk factor for coronary heart disease (CHD)?

Low-density lipoproteins (LDL) are the most atherogenic lipoprotein.

What is the role of high-density lipoprotein (HDL) in cholesterol transport?

HDL scavenges cholesterol from tissues and carries it to the liver for disposal.

What is the process by which HDL transfers cholesterol to LDL?

Cholesteryl Ester Transfer Protein (CETP) facilitates the transfer of cholesteryl esters from HDL to LDL.

What is the significance of lipoprotein (a) in lipid metabolism?

Lp(a) links lipid metabolism with blood coagulation and has atherogenic and thrombogenic potential.

What is hyperlipidemia?

A condition characterized by elevated levels of lipids in the blood, often screened by total cholesterol and lipid profiles.

What methodologies are commonly used for cholesterol measurement?

Cholesterol oxidase is the most common enzymatic procedure for cholesterol measurement.

What happens to VLDL during fasting?

VLDL levels decrease during fasting.

What occurs when there is an excess intake of carbohydrates?

VLDL production increases.

What is the role of acyl-cholesterol acyltransferase (ACAT) in cholesterol metabolism?

ACAT converts free cholesterol to esterified cholesterol for storage.

What is the fate of LDL after it is engulfed by cells?

LDL is degraded by lysosomal enzymes through endocytosis.

What percentage of total cholesterol in plasma is carried by LDL?

Approximately 70%.

What is the composition of HDL?

HDL is composed of proteins and lipids, primarily responsible for reverse cholesterol transport.

What is the function of chylomicrons in the body?

Chylomicrons transport dietary triglycerides from the intestine to various body tissues.

What is the effect of excess cholesterol on LDL receptors?

Excess cholesterol decreases the number of LDL receptors on cells.

What is the relationship between Lp(a) and coronary heart disease risk?

Elevated Lp(a) levels are correlated with increased risk of coronary heart disease.

What is the primary component of the LDL membrane?

The LDL membrane is almost exclusively composed of Apo B-100.

What enzyme oxidizes free cholesterol to yield hydrogen peroxide?

Cholesterol oxidase

What are the interfering substances in the cholesterol oxidation reaction?

Bilirubin, ascorbic acid, and hemoglobin

What is the desirable cholesterol level in mg/dL?

200 mg/dL

What is the recommended fasting duration for triglyceride testing?

12-hour fast required

What is the first step in triglyceride analysis?

Hydrolysis of the triglyceride molecule to glycerol and three fatty acids

What is the desirable triglyceride level in mg/dL?

What is the significance of HDL-C levels ≥60 mg/dL?

Desirable range for High-Density Lipoprotein cholesterol

What is the Friedewald formula used for?

Calculating LDL cholesterol (LDL-C)

What is the LDL-C calculation formula?

LDL-C = (total cholesterol) - (HDL-C + TG/5)

What is the major risk factor for coronary artery disease (CAD) according to NCEP?

Low HDL (< 40 mg/dL)

What are some secondary causes of elevated LDL?

Diabetes Mellitus, hypothyroidism, obstructive liver disease, chronic renal failure

What defines metabolic syndrome according to the American Heart Association?

Presence of three or more risk factors including elevated waist circumference, triglycerides, fasting glucose, reduced HDL, and elevated blood pressure

What is hypercholesterolemia most closely linked to?

Heart disease

What is familial hypercholesterolemia (FH)?

A genetic abnormality predisposing individuals to elevated cholesterol levels

What is the classification for very high triglyceride levels?

500 mg/dL

What is combined hyperlipoproteinemia (CH)?

Elevated levels of serum total cholesterol and triglycerides

What is hypolipoproteinemia?

Low levels of lipoproteins

What characterizes hypoalphalipoproteinemia?

Isolated decrease in circulating HDL (<40 mg/dL) without hypertriglyceridemia

What is hypobetalipoproteinemia associated with?

Isolated low levels of LDL-C due to a defect in the ApoB gene

What does non-HDL cholesterol reflect?

Total cholesterol minus HDL-C

What is the impact of elevated non-HDL-C?

Increased risk of cardiovascular disease (CVD)

What is the primary cause of arteriosclerosis?

Deposits of lipids, particularly esterified cholesterol, in artery walls

What is the relationship between age and lipid levels?

Total and LDL cholesterol & triglyceride levels increase with age

What happens to HDL cholesterol levels in boys at puberty?

Boys' HDL cholesterol drops 20% to adult male levels

What is the leading cause of death and disability in the U.S.?

Arteriosclerosis

What is the significance of the Adult Treatment Panel III (ATP III)?

Identifies algorithms for assessing patients for risk of CAD