Lipids and Lipoproteins

Lipids can be classified into four main groups.

1. simple lipids

2. compound lipids

3. derived lipids

4. miscellaneous lipids

What are simple lipids?

Esters of fatty acids with an alcohol.

• natural fats (triglycerides)

• waxes (including cholesterol esters, vit A/D esters)

What are compound lipids?

Lipids containing fatty acids, an alcohol and an additional non-lipid component (e.g. phosphate group, sugar, amino acid, etc.).

• phospholipids

• glycolipids

• lipoproteins

• aminolipids (proteolipids)

• sulpholipids

What are derived lipids?

Lipids formed from hydrolysis of simple or compound lipids.

• fatty acids

• mono or di-glycerides

• alcohol (e.g. glycerol)

• cholesterol and steroids

What type of lipids are Vitamin K and Vitamin E?

miscellaneous lipids

What are the four forms of lipids in plasma?

1. fatty acids

2. triglycerides

3. phospholipids

4. cholesterol

What is the difference between saturated and unsaturated fatty acids?

• saturated (C-C)

• unsaturated (C=C)

Which type of fatty acid is solid at room temperature?

saturated (higher melting point)

Which type of fatty acid increases LDL (bad cholesterol)?

saturated

What is the structure and function of triglycerides?

3 fatty acids attached to a glycerol via ester bonds

• energy storage

• thermal and water insulation

What is the structure and function of phospholipids?

glycerol + phosphate head attached to two acid chains (one saturated and one unsaturated)

• energy storage

• surfactant

• thermal and water insulation

• phospholipid bilayer

What is the structure and function of cholesterol?

amphipathic (hydrophobic and hydrophilic parts)

• membrane stability

• steroid hormone precursor (e.g. testosterone)

• vitamin D precursor

• protective agent for skin

Cholesterol is synthesised from _________

acetyl CoA

What are the main biological roles of lipids?

• energy storage (e.g. triglycerides)

• structural role (e.g. phospholipid bilayer)

• enzyme cofactors (e.g. coenzyme Q in ETC)

• steroid hormones (e.g. cholesterol → androgens)

• membrane anchors (e.g. glycolipids)

• signalling messengers (e.g. prostaglandins)

Lipids are insoluble in water. How are lipids transported in the blood?

lipoproteins

What is the structure of lipoproteins like?

non-polar core of triglycerides and cholesterol esters surrounded by phospholipids, free cholesterol and apolipoproteins

What are the four main lipoproteins?

1. chylomicrons

2. VLDL (very-low density)

3. LDL (low density)

4. HDL (high density)

How does composition of the lipoproteins change?

from biggest to smallest

• protein content increases

• lipid content decreases

Which two lipoproteins are produced by the liver?

• VLDLs

• HDLs

What is the function of chylomicrons?

Transport exogenous triglycerides from small intestine to all cells.

Chylomicron remnants return to liver

What is the function of VLDLs?

Transport endogenous triglycerides produced in the liver to cells.

What is the function of LDLs? How are they produced?

LDLs are produced from VLDL → IDL

Transport cholesterol to cells.

What is the function of HDLs?

Transport excess cholesterol from cells back to the liver.

What are the four types of apolipoproteins and what are their functions?

1. A

2. B

3. C

4. E

Apolipoprotein A is found in which lipoprotein?

• Chylomicrons

• HDL

Cofactor for LCAT (enzyme for lipid metabolism)

Apolipoprotein B is found in which lipoprotein?

• Chylomicrons

• VLDL

• LDL (and IDL)

(All except HDL)

Secretion of chylomicrons and VLDLs, binding of LDL to receptor.

Apolipoprotein C is found in which lipoprotein?

• Chylomicrons

• VLDL

• HDL

• IDL

(All except LDL)

Cofactor for lipoprotein lipase enzyme

Apolipoprotein E is found in which lipoprotein?

• Chylomicrons

• VLDL

• HDL

• IDL

(All except LDL)

Which lipids are exogenous and which are endogenous?

• exogenous- TGs, FAs

• endogenous- PLs, CH

Examples of lipid disorders

• dyslipidaemia

• hyperlipidaemia

• hypercholesterolaemia

• hypertriglyceridemia

• mixed hyperlipidaemia

Dyslipidaemia is characterised by?

• high LDL (cholesterol)

• low HDL

Hypertriglyceridemia is characterised by?

• high TG (chylomicrons, VLDLs)

Hypercholesterolaemia is characterised by?

• high total cholesterol

• high LDL

• high VLDL

• low HDL

Hyperlipidaemia is characterised by?

• high LDL (cholesterol)

• high TG

Mixed hyperlipidaemia is characterised by?

• high LDL (cholesterol)

• high VLDL (TG)

Familial hyperlipidaemias are classified according to the _____________ Classification in which there are ___ phenotypes depending on levels of lipoproteins in blood.

Fredrickson Classification

Six phenotypes

Examples of acquired causes of lipid disorders

• diabetes

• hypothyroidism

• nephrotic syndrome

• medication

Which medications cause acquired lipid disorders?

Beta blockers

Estrogen

Thiazides

Clinical manifestations of hyperlipidaemia include

Hyperlipidaemia is characterised by high LDL, high TG

Accumulation of lipids in:

• tissues

• arterial walls (atherosclerosis)

• subcutaneous tissues (xanthomatosis- fats build up under skin)

• tendons

• cornea

What are the three types of xanthoma?

1. eruptive

2. tuberous

3. xanthelasma

What is eruptive xanthomata characterised by?

sudden outbreaks of small, yellow-red bumps on the skin, caused by high VLDL or chylomicron (TGs)

treatable

What is tuberous xanthomata characterised by?

plaques found over elbows and knees caused by high IDL

What is xanthelasma characterised by?

lipid deposits under periorbital skin associated with high LDL (cholesterol)

What is tendinous xanthomata?

What is cornea arcus?

caused by high cholesterol

What is hypolipidemia?

rare disorder associated with low plasma lipid levels AND tissue accumulation despite low plasma levels.

How is lipid measured in the laboratory?

• total cholesterol

• HDL cholesterol

• triglycerides

• LDL triglycerides (measured and calculated)

• total cholesterol : HDL cholesterol ratio

How can LDL cholesterol be measured without the use of a centrifuge?

Friedewald formula- used to estimate LDL ("bad") cholesterol from a standard lipid panel:

The Friedewald formula is reasonably accurate but when can it be unreliable?

• When TGs are high due to effects of VLDLs and LDLs