BIOC L10 - lipid transport

What is cholesterol?

is a sterol, very insoluble and important for membranes to control fluidity

Where is cholesterol distributed?

widely but greatest demands are the liver and reproductive tissues

What is the structure of cholesterol?

has a steorid ring which helps with the solubility of fats but steroid ring cannot be degraded so excreted as bile

Where does cholesterol come from in the diet?

animal products

Apart from membranes what else is cholesterol important for?

precursor for steroid hormones (andorgens) and bile acids and vitamin D, major constituent of lipoproteins, transporting fat soluble vitamins, neuronal function

Why can cholesterol can be bad?

over time, can form plaques on the inside walls of blood vessels which can build up and cause blockages which can cause heart attacks or shortages

What is the structure of lipoproteins?

has a phospholipid bilayer which contains apoproteins and unesterified cholesterol, contains a hydrophobic centre with TAGs and esterified cholesterol

What are the classes of lipoproteins?

chylomicrons (exogenous, triglyceride rich), very low density lipoprotein (VLDL, endogenous, triglyceride rich), low density lipoprotein (LDL, cholesterol rich), high density lipoprotein (HDL, cholesterol and protein rich)

What should cholesterol status be when fasting?

<4mmol/L

How are chylomicrons synthesised?

in the intestines use apoB48, microsomal triglyceride transport protein (MTP) ensures lipids and TAGs are transferred from cytoplasm to endoplasmic reticulum to form apoB particle then add more TAGs to make a mature apoB particle

What is the exogenous pathway of lipoprotein metabolism?

chylomicrons exit the intestinal cells and travel to the bloodstream via the lymphatic system, they deliver fatty acids to adipose for storage and muscle for consumptionn then are broken down by LPL on capillary surfaces in chylomicron remnants which travel to the liver

What is the endogenous pathway of lipoproteins?

TAGs, cholesterol and VLDL are made in the liver

What is the role of lipoproteins?

solubilise lipids for transport in blood tissues, LDLR involved in lipid uptake in cells

What is the role of apoproteins?

assembly/synthesis (apoB), ligands for cell surface proteins

What factors affect lipid levels?

diet: saturated fat vs unsaturated fat, drugs e.g. statins and fibrates, genetics e.g. variance in apoB, disease such as diabetes

What dietary changes can reduce LDL cholesterol?

eating soyprotein, nuts and plant sterols, also the meditarranean diet as it contains a lot of omega-3 fatty acids but also is rich in fibre and antioxidants

What are fibrate effects on triglycerides?

fibrates lower lipids and interact with PPAR molecules (receptors associated with lipolysis) increasing lipase activity which increases lipolysis and reduces TGs

What do PPARs do?

indirectly alter the synthesis of lipoproteins

Why do keto diets increase blood cholesterol?

keto diets are low in carbs but high in protein (contains saturated fats) and fat

What do statins do to TGs?

statins inhibit HMGCoA reductase activity reducing intracellular cholesterol and upregulating LDL receptors which enhances LDL uptake lowering levels in the blood

What would happen if there was a defect in LDLR?

LDLR is low density lipoprotein receptor which is repsonsible for uptake of LDL from the bloodstream, without it levels of LDL would increase

What would happen if there was a defect in ApoCII?

ApoCII is the activator of lipoprotein lipase which is requird to break down chylomicrons and VLDL, without it there will be high levels of chylomicrons and TGs

What would happen if there was a defect in ApoB?

ApoB is responsible for the sythesis of chylomicrons (ApoB48) and VLDL (ApoB100), without it there would be fewer lipoproteins so less TGs and LDL