X-Lipids and Lipoproteins Disorders Part I and II

What are lipids?

They are organic compounds that are primarily esters of fatty acids. They are soluble in organic solvents but nearly insoluble in water, making them hydrophobic

What are lipoproteins?

They are transport molecules for lipids, helping to carry these hydrophobic compounds through the bloodstream and other aqueous environments in the body.

What are the major types of lipids?

• Cholesterol.

• Triglycerides

• Phospholipids

• Glycolipids.

What does triglycerides consist of

3 fatty acids and glycerol.

What do phospholipids consist of

2 fatty acids, glycerol, and a polar head.

What is the role of lipids in cellular structure?

They are part of the structural components of cells, such as phospholipids in the lipid bilayer, which form the cell membrane.

How do lipids serve as an energy source?

They are a major energy source, providing 9 calories per gram. They are broken down through β-oxidation in the mitochondria to produce energy.

What role do lipids play in digestion and absorption?

Through the production of bile acids (made from cholesterol), which aid in the emulsification of fats for absorption in the intestines.

How do lipids serve as hormones?

steroid hormones, serve as important hormones in the body, playing roles in regulating various physiological processes.

What are cholesterol and its structure?

It is a sterol and a steroid alcohol, meaning it has a steroid backbone. It is the most common sterol in humans and is primarily found in animals and humans.

What is the basic structure of cholesterol?

It contains 27 carbon atoms and has four fused rings labeled A, B, C, and D, which make up its core/nucleus. These rings form the perhydro cyclopentano phenanthrene nucleus.

What does "phenanthrene" refer to in the context of cholesterol?

It refers to three fused benzene rings that form part of the steroid backbone of cholesterol, with a hydroxyl (OH) group at position 3.

What is the branched aliphatic chain in cholesterol?

It has 8 or more carbon atoms at position 17 in its structure.

What is the role of cholesterol in cell membranes?

It is an essential structural component of the cell membranes, where it is embedded within the lipid bilayer. It helps maintain membrane fluidity, stability, and permeability.

How is cholesterol related to bile acids?

It serves as a precursor for the synthesis of bile acids, which are important for the digestion and absorption of fats.

What is cholesterol's role in vitamin D synthesis?

It acts as a precursor of vitamin D through its derivative 7-Dehydrocholesterol. This compound is involved in the production of vitamin D when exposed to sunlight.

How is cholesterol involved in the production of steroid hormones?

It is the precursor of all steroid hormones, including sex hormones and adrenal hormones. This is especially important for adrenal gland function.

Where is exogenous cholesterol found?

In animal products, especially in meat and egg yolk.

How is exogenous cholesterol absorbed and processed?

Exogenous cholesterol from the diet is absorbed in the intestine, then it enters the circulation and is transported to the liver for processing.

What is endogenous cholesterol and how is it produced?

It is produced by the liver from simpler molecules, particularly acetate, a short-chain fatty acid (SCFA), which is converted into acetyl CoA.

How much endogenous cholesterol is synthesized daily?

500 to 1000 mg.

How is the synthesis of endogenous cholesterol regulated?

It is regulated by a feedback mechanism based on the levels of exogenous cholesterol. The higher the level of exogenous cholesterol, the less the body manufactures endogenous cholesterol.

How does serum cholesterol concentration change with age?

It starts around 65 mg/dL at birth and steadily increases with age at a rate of approximately 1.5 mg/dL per year.

What is 3-hydroxy-β-methylglutaryl CoA (HMG-CoA) reductase?

It is the rate-limiting enzyme for cholesterol synthesis, playing a critical role in the production of cholesterol in the liver.

How do statin drugs affect HMG-CoA reductase?

Statin drugs (such as Advicor, Lipitor, and Crestor) inhibit HMG-CoA reductase, thereby reducing the synthesis of cholesterol in the liver.

What is the role of Lecithin–cholesterol acyltransferase (LCAT)?

It is a plasma enzyme that catalyzes cholesterol esterification in the intravascular space. This process helps in raising HDL cholesterol levels, which is beneficial for cardiovascular health.

What is the role of hepatic HMG-CoA reductase in cholesterol synthesis?

It is the rate-limiting enzyme in cholesterol synthesis in the liver. It is subject to induction and repression depending on the level of cholesterol in the body.

How does feedback control regulate cholesterol synthesis?

Feedback control of hepatic cholesterogenesis is mediated by cholesterol itself and bile acids. When cholesterol levels are high, cholesterol is converted into bile acids and excreted through feces. This helps reduce cholesterol levels in the body.

How are bile acids related to cholesterol?

Bile acids are synthesized from cholesterol. When cholesterol levels are high, the liver converts excess cholesterol into bile acids, which are then excreted via the feces.

How do hormones regulate cholesterol synthesis?

Growth hormone and thyroid hormone regulate HMG-CoA reductase and help reduce cholesterol levels in the body. For example, patients with hypothyroidism (underactive thyroid) tend to have high cholesterol levels.

What form is cholesterol typically found in the intestine?

Practically all cholesterol in the intestine is present in its unesterified form (free cholesterol).

Why is cholesterol in the intestine in unesterified form?

Esterified cholesterol is rapidly hydrolyzed by cholesterol esterases, which are secreted by the pancreas and small intestine.

What role do cholesterol esterases play in the intestine?

They hydrolyze esterified cholesterol into its free cholesterol form, facilitating its absorption.

How does the hydrolysis of cholesterol facilitate absorption?

It sets the conditions for mixed micelle formation, which helps facilitate the uptake of cholesterol by enterocytes (intestinal cells).

What happens when cholesterol becomes esterified?

It loses its free hydroxyl group and becomes much more hydrophobic. This change causes it to move from the surface of lipoprotein particles to the hydrophobic core.

Where is esterified cholesterol bound in the body?

It is primarily bound to lipoproteins, particularly high-density lipoproteins (HDL).

How much of the total cholesterol in plasma is in the form of cholesteryl esters?

70%

What is involved in the activation of fatty acids?

They are activated by a reaction with CoA to form fatty acyl CoA, which is an ATP-requiring reaction. This process yields AMP and pyrophosphate (PPi).

What does "acyl" refer to in the context of fatty acids?

It refers to an acid derivative, such as a fatty acid, which is involved in the formation of fatty acyl CoA.

What are fatty acids and what forms do they take?

They are the simplest form of lipids. They can be either saturated or unsaturated.

What characterizes saturated fatty acids?

They contain an alkyl chain without any double bonds between the carbon atoms.

What type of fatty acid chains are most common in saturated fatty acids?

Even-numbered fatty acids

What are examples of common saturated fatty acids?

• Palmitic acid (16:0)

• Stearic acid (18:0), also known as octadecanoic acid

What is the difference between monounsaturated and polyunsaturated fatty acids?

• Monounsaturated fatty acids (MUFA) contain one double bond in their structure.

• Polyunsaturated fatty acids (PUFA) contain more than one double bond, with the double bonds typically spaced three carbons apart.

What is the configuration of the double bonds in fatty acids?

They are nearly always in the cis configuration

What are non-essential fatty acids?

They are fatty acids that can be synthesized by the body and do not need to be obtained from the diet.

What fatty acids are produced by mammals and what are they used for?

They can produce saturated fatty acids and monounsaturated fatty acids (MUFA), which are used primarily for fuel (energy).

What are essential fatty acids?

They are fatty acids that cannot be synthesized by the body and must therefore be obtained from the diet.

What are examples of essential fatty acids

linoleic acid and linolenic acid (both are polyunsaturated fatty acids (PUFA)).

What is the role of essential fatty acids in the body?

They are important for signaling rather than being used as energy. They are required for the biosynthesis of prostaglandins, which play a role in regulating blood pressure by affecting arterial smooth muscle cells.

What is glycerol?

It is a 3-carbon molecule that contains three hydroxyl groups (-OH).

What are glycerol esters?

They are one of the common alcohols (fatty alcohols) found in human metabolism.

What is an acylglycerol or acylglyceride?

It is the product of the esterification of glycerol with fatty acids. They are classified as mono-, di-, or tri-acylglycerides based on the number of fatty acids attached to the glycerol molecule.

What are triglycerides?

They are the most common glycerol esters (acylglycerols) found in plasma.

What are triglycerides composed of

glycerol and three fatty acids (FAs) linked via ester bonds.

What other forms of acylglycerols are found in the body?

monoacylglycerol (MG), diacylglycerol (DG), and triacylglycerol (TG). Among these, triacylglycerol (TG) is the most abundant.

What role do triglycerides play in the body?

They are the most abundant family of lipids in animal cells and are major components of the human diet. They are primarily used for energy storage and are metabolized through a process called lipolysis.

What is lipolysis?

It is the breakdown of triglycerides (TG) to release fatty acids for energy use.

What is lipolysis facilitated by?

lipases, including lipoprotein lipase

What is lipolysis stimulated by?

Hormones like epinephrine and cortisol, particularly during the fight or flight response when there is high energy demand.

Where is triglyceride (TG) synthesized after absorption?

They are assembled in the intestinal epithelium, where they are packaged by combining with cholesterol (Chl-E), phospholipids (PL), and apolipoprotein B-48. This forms chylomicrons, which contain B-48.

What role does HDL play in triglyceride synthesis in the intestine?

It plays an important role in the packaging process by providing Apolipoprotein CII (Apo CII) and Apolipoprotein E (Apo E) for the chylomicrons.

How is triglyceride synthesis accelerated in the liver?

It is accelerated by a diet rich in simple sugars, where excess calories drive the production of triglycerides. This leads to an overproduction of VLDL (very low-density lipoproteins), which can result in hypertriglyceridemia.

What role does HDL play in the synthesis of VLDL in the liver?

by providing Apolipoprotein CII (Apo CII) and Apolipoprotein E (Apo E) for the synthesis of VLDL.

What happens to VLDL triglycerides during fasting?

They are catabolized and consumed. The metabolic pathways in the liver are reversed, leading to a decrease in hepatic VLDL triglyceride synthesis. This occurs as blood glucose concentrations fall, and insulin levels diminish, preventing the storage of triglycerides in adipocytes.

Where are phospholipids synthesized?

in the liver.

How are phospholipids related to triglycerides?

They are similar, but phospholipids contain an additional group. They consist of one phosphate molecule and two fatty acid molecules attached via ester bonds.

What are the different types of polar heads in phospholipids?

• Choline – forming phosphatidylcholine.

• Serine – forming phosphatidylserine.

• Hydrogen – forming diacylphosphoglyceride.

Where are phospholipids found in the body?

on the surface of lipid layers (outer core) and are major constituents of cell membranes.

Why are phospholipids important for lipoproteins?

They are major constituents of the outer shells of lipoprotein molecules. This is important because they help maintain the stability and structure of lipoproteins, allowing them to transport lipids in the bloodstream effectively.

What are glycolipids composed of?

a sugar residue and a lipid residue, which are linked by an ester bond.

What is the role of glycolipids in the body?

1. essential components of cell membranes

2. help determine blood groups

3. act as receptors on the surface of red blood cells

4. play a role in immune response by interacting with viruses and bacteria.

How do glycolipids interact with viruses and bacteria?

Some viruses and bacteria (such as cholera) use glycolipids on the surface of their cells. This interaction helps the immune system recognize and destroy pathogens from the body.

What are apolipoproteins?

They are proteins found as an integral part of lipoprotein molecules.

What are apolipoproteins classified as

five major categories: Apo A, B, C, D, and E, each with several subcategories.

What is the function of apolipoproteins?

• Activating enzymes involved in lipid metabolism (acting as cofactors).

• Maintaining structural integrity of the lipid/protein complex.

• Facilitating delivery of lipids to cells by recognizing cell surface receptors (acting as ligands).

• Promoting solubility of lipids in plasma.

How does HDL ApoA-I function in lipid metabolism?

It acts as a cofactor and is the principal catalytic activator for Lecithin-cholesterol acyltransferase (LCAT), which is a plasma enzyme involved in cholesterol esterification (intravascular).

What is the role of ApoC-II in lipid metabolism?

It is required for the activation of lipoprotein lipase (LPL), which is involved in the hydrolysis of triglycerides (TG), facilitating their metabolism.

How do apolipoproteins facilitate lipid delivery to cells?

Apolipoproteins, such as ApoE, facilitate the delivery of lipids to cells by recognizing cell surface receptors and acting as ligands.

What are lipoproteins?

They are spherical particles that transport lipids. They are complex micellar (aggregate) structures consisting of an outer layer and an inner core.

What is found in the outer layer of lipoproteins?

• Proteins (apolipoproteins).

• Amphipathic polar lipids (e.g., phospholipids).

• Unesterified (free) cholesterol.

What is found in the inner core of lipoproteins?

• Triglycerides.

• Esterified cholesterol.

What is the hydrophobic nature of lipoproteins?

The inner core of lipoproteins is hydrophobic (repels water), which helps in the transport of lipids through the aqueous environment of the bloodstream.

What is the function of lipoproteins?

Once lipids are synthesized in the intestine or liver, they require lipoproteins to be transported to various organs and tissues for their metabolic functions.

Can you give examples of lipoproteins and their roles?

• Chylomicrons (CM): Transport lipids from the intestine to other parts of the body.

• Very Low-Density Lipoproteins (VLDL): Transport lipids from the liver to various tissues.

What are the five categories of lipoproteins?

• Chylomicrons (ULDL) – Floats and is large.

• Very-Low-Density Lipoproteins (VLDL).

• Intermediate-Density Lipoproteins (IDL or LDL1) – Transitional state.

• Low-Density Lipoproteins (LDL).

• High-Density Lipoproteins (HDL) – Dense and small.

What are chylomicrons?

They are triglyceride-rich lipoproteins produced by the intestine. They transport dietary lipids from the intestine to the liver and peripheral cells

What is the size and density of chylomicrons?

They are the largest lipoproteins by size but have the least density.

What is the composition of chylomicrons?

They are primarily composed of lipids, with 90% triglycerides and 1% protein.

What apolipoproteins are incorporated into chylomicrons?

Apo-B48, Apo-CII, and Apo-AI. Apo-E

What happens to lipid-poor chylomicron remnants?

They are removed by the liver through Apo B/E receptors.

What is the main function of chylomicrons?

They are responsible for transporting dietary (exogenous) fats, mainly triglycerides, from the intestines to the liver and peripheral cells (such as muscle and adipocytes).

What is the structure of chylomicrons?

They have triglycerides and esterified cholesterol packed into their core, while the apolipoproteins are incorporated into the membrane.

What is VLDL and how is it produced?

It is a triglyceride-rich lipoprotein produced by the liver as part of the endogenous pathway. It transports liver-synthesized fat (mostly triglycerides) to peripheral tissues such as fat and muscle cells.

What is the composition of VLDL?

It is mainly composed of lipids, with about 55% triglycerides and 10% protein.

What are the primary apolipoproteins in VLDL?

Apo-B100, Apo-CII, and Apo-E.

How does VLDL function in the body?

It is used for metabolism and clearance by the liver. Apo-B100 facilitates the uptake of VLDL from the blood via Apo-B/E receptors on liver cells.

What happens if there is a defect in VLDL clearance?

an increase in triglycerides (TG) in the blood, contributing to hypertriglyceridemia.

What are VLDL remnants, and how are they cleared?

They are also known as intermediate-density lipoproteins (IDL). These remnants are cleared by the liver through Apo-B/E receptors, similar to the process for VLDL uptake.

What is the clinical significance of VLDL

Familial Hypertriglyceridemia (excess VLDL)

Heterozygous deficiency of lipoprotein lipase (LPL)