Biochemistry of hyperlipidemia

Question 1

Definitions

Answer 1

• Hyperlipidemia: elevated lipids in the blood
• Lipoproteins: particles in blood transporting lipids btwn tissues (contains cholesterol, esters, TAGs, phospholipids)
• Apolipoproteins: protein component of lipoproteins
• Hyperlipoproteinemia: high levels of lipoproteins in the blood
• Hypercholesterolemia: elevated blood cholesterol
• Hypertriglyceridemia: elevated blood triglycerides

Question 2

Structures of lipids

Answer 2

• Phospholipids are made in all tissues but mostly liver
• Polar group (R3): choline, ethanol amine, serine
• TAGs made in liver and stored in adipose and muscle, major energy source for body except brain
• Cholesterol is hydrophobic w/ OH group (amphiphatic), esters are 100% hydrophobic
• Both found in membranes of all tissues
• Cholesterol is precursor for bile acids and steroid hormones (golgi, SER)

Question 3

Cholesterol synthesis

Answer 3

• Most cholesterol is synthesized by the body, only 10-25% is absorbed from diet
• Rate limiting step in cholesterol synthesis: HMG-CoA -> mevalonic acid via HMG-CoA reductase (requires 2 NADPH)

Question 4

Diseases associated w/ hyperlipidemia

Answer 4

• Main ones: CVD, atherosclerosis, CAD, MI, stroke, obesity, diabetes
• Also: ischemic colitis, metabolic syndromes, pancreatitis/pancreatic CA, non-alcoholic fatty liver, xanthoma, xanthelasma (eyelids)

Question 5

Lipoproteins and apolipoproteins

Answer 5

• Lipoproteins consist of lipids and apolipoproteins
• ApoA, B, C and E are found on the surface along w/ PLs
• TAGs and cholesterol are found on the inside
• Chylomicrons produced in intestine (well fed state), taken to the liver to be converted into VLDL, and then converted to other forms (LDL, IDL, and HDL) in liver
• LDL used to deliver liver cholesterol to other tissues via uptake of LDL thru surface receptors
• From least->most dense: chylomicrons, VLDL, IDL, LDL, HDL
• The only good one is HDL