Hepatic System Part 2 (cholesterol)

Cholesterol

A sterol molecule found in all body cells as part of the cell membrane.

dietary cholesterol

25%

synthesised cholesterol

75%

primary cholesterol synthesis

occurs in the cytoplasm and endoplasmic reticulum of the liver

secondary cholesterol synthesis

small amounts synthesised by the lining of the small intestine and individual cells of the body

HMG-CoA reductase reaction

Rate limiting step of cholesterol synthesis. Highly regulated and often targeted by pharmacological intervention

Triparanol

A drug that inhibits a late step in the cholesterol synthesis pathway, but was withdrawn due to adverse effects and cataract development.

Desmosterol

substrate of the enzyme inhibited by Triparanol which accumulated → side effects

Membrane permeability

Cholesterol reduces membrane permeability as its hydroxyl group interacts with the polar heads of membrane phospholipids and sphingolipids, increasing membrane packing.

Sex hormone production

Cholesterol is involved in producing progesterone, oestrogen and testosterone

Adrenal hormones

Cholesterol is essential for production of hormones released by the adrenal gland eg cortisol and aldosterone

Cortisol

increases blood sugar levels through gluconeogenesis and aids in fat, protein and carbohydrate metabolism.

Aldosterone

A hormone that regulates sodium and potassium levels, controlling blood pressure.

Bile acid production

Cholesterol aids in the production of bile acids, which work to digest food in the intestines.

Nerve insulation

Cholesterol insulates nerve fibres

Vitamin D synthesis

Cholesterol is involved in the process of synthesizing vitamin D from sunlight.

Atherosclerosis

Narrowing of arteries. Increases risk of coronary heart disease

Coronary heart disease

An abnormality in the coronary arteries

Heart attack

Occurs when heart’s blood supply is blocked, usually by a clot in the coronary artery → heart muscle death

Angina

Chest pain/discomfort which occurs when the heart muscle doesn't receive enough oxygen

Stroke/mini-stroke

Occurs when a blood clot blocks an artery/vein supplying the brain, or as a result of a blood vessel breaking (aneurysm).

Plaque rupture

Plaques that build up in the arteries may rupture and enter the bloodstream, potentially leading to blockage of coronary or carotid arteries

What are the different classifications of lipoproteins?

chylomicrons, VLDL, IDL, LDL and HDL. Varying fat to protein ratios

LDL

Carry cholesterol from the liver to cells

what % of blood lipoprotein is LDL?

70%

Cholesterol transport

cholesterol insoluble in the blood so is transported via lipoproteins

HDL

High-density lipoproteins carry cholesterol away from cells back to the liver, where cholesterol is broken down or expelled from the body.

Chylomicrons

Lipoproteins that carry triglycerides from the intestine to the liver, skeletal muscle and adipose tissue

VLDL

carry newly synthesised triglycerides from the liver to adipose tissue.

Risk factors for high blood cholesterol

Diet, medical conditions, genetics, sex, age, smoking, inactivity and obesity

Statins

inhibit early, rate limiting step in cholesterol biosynthesis

how does inactivity/obesity increase risk of high blood cholesterol?

Inactivity can increase LDL cholesterol levels. Obesity may increase triglycerides and LDLs and decrease HDLs.

hyperlipidaemia

may be familial (primary) or acquired (secondary). Secondary hyperlipidaemia results from another underlying disorder leading to alterations in plasma lipid and lipoprotein metabolism. May also be idiopathic.