Lipids and lipoproteins CHEM

What physical property defines lipids, unlike other major biomolecules?

They are soluble in organic solvents but nearly insoluble in water.

What is the primary structural feature of lipids and what do they yield upon hydrolysis?

They primarily contain nonpolar carbon-hydrogen (C-H) bonds and yield fatty acids and/or complex alcohols after hydrolysis.

What are three structural roles lipids play in the body?

Structural components, hormones, and nerve insulators.

What is the clinical significance of lipids?

Their link to coronary heart disease (atherosclerosis), cardiovascular disease, and lipoprotein disorders.

What are the six broad subdivisions of lipids?

Cholesterol, fatty acids, acylglycerols, sphingolipids, prostaglandins, and terpenes.

In which organisms is cholesterol found almost exclusively?

Animals.

What are three key functions of cholesterol in the body?

Key membrane component of cells, precursor for bile acids, and precursor for steroid hormones.

What is the four-ring structure of cholesterol called?

Cyclopentanoperydrophrenanthrene.

What percentage of dietary cholesterol is typically absorbed?

~30% to 60%.

Which enzymes act on dietary cholesterol in the pancreas and small intestine?

Cholesterol esterases.

How are dietary cholesterol and fats delivered to the liver and peripheral tissues?

By chylomicrons.

Which organs are particularly active in cholesterol synthesis?

The liver and intestine.

What are the basic steps of cholesterol synthesis starting from Acetyl CoA?

Acetyl CoA → mevalonic acid → squalene → lanosterol → cholesterol.

Which enzyme catalyzes the rate-limiting step in cholesterol synthesis?

HMG-CoA reductase.

What class of drugs inhibits HMG-CoA reductase?

"Statin" drugs.

What are the two enzymes that esterify cholesterol and where do they act?

ACAT (in cells) and LCAT (in plasma).

What form of cholesterol accounts for ~70% of total cholesterol in plasma?

Cholesterol esters.

Why does cholesterol become more hydrophobic when it forms a cholesteryl ester?

It loses its free hydroxyl group.

Where does the majority of cholesterol catabolism occur?

In the liver.

What fraction of daily cholesterol production is converted into bile acids?

~1/3.

What can precipitate to form gall stones when cholesterol exceeds capacity?

Cholesterol.

What is the general chemical formula for a fatty acid?

RCOOH.

How are fatty acids classified?

By chain length and degree of saturation.

What is a saturated fatty acid?

A fatty acid with no double bonds between carbon atoms.

What is a monounsaturated fatty acid?

A fatty acid containing one double bond.

What is a polyunsaturated fatty acid?

A fatty acid containing multiple double bonds.

Where are fatty acids catabolized in the cell?

In the mitochondria.

What process produces energy from fatty acids by shortening the chain by 2 carbons at a time?

β-oxidation.

A 16-carbon fatty acid yields how many acetyl CoA molecules?

8 molecules.

What does acetyl CoA condense with to enter the Krebs cycle?

Oxaloacetate (to yield citrate).

What is the definition of an acylglycerol?

An ester of glycerol with one or more fatty acids.

What is a monoacylglycerol?

A glycerol with one fatty acid.

What is a diacylglycerol?

A glycerol with two fatty acids.

What is a triacylglycerol also known as?

Triglyceride.

What percentage of tissue storage fat is triglycerides?

95%.

What is the predominant form of glycerol esters found in plasma?

Triglycerides.

Generally, what is the state and fatty acid composition of plant triglycerides at room temperature?

Liquids, enriched in unsaturated FAs.

Generally, what is the state and fatty acid composition of animal triglycerides at room temperature?

Solids, containing saturated FAs.

What amino alcohol are sphingolipids derived from?

Sphingosine.

What are three intermediate structures formed from sphingosine?

Sphingomyelin, galactosylceramide, glucosylceramide.

What is the biological function of sphingolipids in cell recognition?

Recognition of cells as self and recognition of blood group antigens.

What complex structures are formed from sphingolipids?

Globosides and gangliosides.

Where are gangliosides abundant?

In the membranes of grey matter of the brain.

What are prostaglandins?

About 20 different tissue hormones.

Where are prostaglandins synthesized?

At the site of reaction.

Why do prostaglandins have a short life?

They are rapidly catabolized.

What are three functions of prostaglandins?

Smooth muscle contractions, glandular secretion, and modulation of other processes.

From which 20-carbon unsaturated fatty acid are prostaglandins made?

Arachidonic acid.

What 5-carbon unit are terpenes made from?

Isoprene.

What fat-soluble vitamins are made from terpenes?

Vitamins A, E, and K.

What plant pigments are terpenes used to make?

Carotenoids (red, yellow, orange pigments).

What is an example of a terpene pigment?

Beta-carotene.

What are the six main classes of lipoproteins?

Chylomicrons, VLDL, IDL, LDL, HDL, and Lipoprotein(a).

What is the structural arrangement of lipoproteins?

Spherical micelle-like particles with a nonpolar core and a polar surface.

What is found in the core of a lipoprotein?

Nonpolar neutral lipids (triglycerides and cholesterol esters).

What is found on the surface of a lipoprotein?

Polar amphipathic lipids and specific proteins called apolipoproteins.

How are lipoproteins traditionally categorized?

Based on differences in their densities.

Why do larger lipoproteins have lighter density?

They contain more core lipids (triglycerides and cholesterol esters).

Rank the four main lipoproteins from largest to smallest.

Chylomicron > VLDL > LDL > HDL.

What is the relative triglyceride content of a chylomicron?

85%.

What is the relative triglyceride content of VLDL?

50%.

What is the relative triglyceride content of LDL?

10%.

What is the relative triglyceride content of HDL?

4%.

What is the primary function of chylomicrons?

Transport lipids from the intestinal mucosa to tissues via the lymph and circulatory systems.

What happens to triglycerides in chylomicrons in the bloodstream?

Hydrolyzed to monoglycerides and fatty acids, which are absorbed by tissues.

What do chylomicron remnants carry to the liver?

Cholesterol.

What is the primary function of VLDL?

Transport triglycerides from the liver to tissues.

What are the remnants of VLDL after triglyceride hydrolysis?

LDL and some IDL.

What is the primary function of LDL?

Transport cholesterol and cholesterol esters to tissues.

How is LDL absorbed by cells?

Receptor-mediated endocytosis.

What happens to LDL after endocytosis?

The cell hydrolyzes the cholesteryl esters, any remaining triglycerides, and the protein.

What is the primary function of HDL?

Remove excess cholesterol from tissues and transport it to the liver.

Why is HDL sometimes called "good cholesterol"?

It helps impede the accumulation of atherosclerotic plaque on blood vessel walls.

What is the structural relationship of Lipoprotein(a) to LDL?

It is structurally related to LDL but contains a carbohydrate protein apo(a).

What determines plasma levels of Lipoprotein(a)?

Mostly genetically.

What is a major clinical association of Lipoprotein(a)?

Aortic stenosis.

Is there adequate drug or dietary therapy for lowering Lipoprotein(a) levels?

No.

What are the protein constituents on the surface of lipoproteins called?

Apolipoproteins.

What are three functions of apolipoproteins?

Activate enzymes involved in lipid metabolism, maintain structural integrity of lipid/protein complex, and deliver lipids to cells via recognition of cell surface receptors.

Which apolipoprotein delivers lipids to cells via receptor recognition?

APO B.

Which apolipoproteins are present on chylomicrons?

AI, B-48, CI, CII, CIII.

Which apolipoproteins are present on VLDL?

B-100, CI, CII, CIII, E.

Which apolipoproteins are present on IDL?

B-100, E.

Which apolipoprotein is present on LDL?

B-100.

Which apolipoproteins are present on HDL?

AI, AII.

What happens to lipids in the mouth during digestion?

Nothing happens.

What begins the digestion of fats in the stomach?

Emulsification by churning action and gastric lipases.

What is the role of bile salts in the small intestine?

Emulsification, acting like soap to break large droplets into small droplets to increase surface area for lipase.

Is emulsification by bile salts a chemical reaction?

No, it is a physical process.

What enzymes hydrolyze lipids in the small intestine?

Pancreatic lipase and intestinal mucosal lipases.

During hydrolysis in the small intestine, what do triglycerides become?

Mono- and di-glycerides.

During hydrolysis in the small intestine, what do cholesteryl esters become?

Free cholesterol.

During hydrolysis in the small intestine, what do phospholipids become?

Lysophospholipids.

What are micelles?

Large aggregates of fat breakdown products and bile acids.

Where does absorption of micelles occur?

When they encounter the microvilli of intestinal cells.

What happens to micelles inside intestinal cells?

They are re-esterified in the Golgi apparatus to form triglycerides and cholesteryl esters.

What is the structure of a chylomicron?

A core of fats surrounded by a shell of phospholipids, apolipoproteins, and free cholesterol.

Why is the outer shell of a chylomicron polar?

It helps for suspension in a watery environment.

What is the route of chylomicrons from the intestine to the bloodstream?

Leave mucosal cells → lacteals (lymph) → thoracic duct → bloodstream at the left subclavian/jugular vein junction.

At which anatomical junction do chylomicrons enter the bloodstream?

Left subclavian/jugular vein junction (at the collar bone).