Lipids

Fats or Lipids are:

Large molecules made up of elements - C, H, O

Fats or Lipids

Hydrogen to Oxygen ratio is higher than 2:1

Fats or Lipids

non polar, insoluble molecules

Fats or Lipids are made up of more than one component:

Glycerol and Fatty Acids

Glycerol

3 carbon molecule each with a hydroxyl group (-OH)

Fatty Acids

are long chains with only carbon and hydrogen in a chain and at the end there will be another group, carboxyl group ( -COOH)

Roles of Lipids

- Source of energy
- Integral part of cellular membranes that assist in cell structure
- Converted to hormones or hormone precursors
- Insulators for nerve conduction and heat retention

Classification of Lipids

Simple and Compound

Simple

Fatty Acids are esterified with glycerol

Compound

Same as simple, but with other compounds also attached

Phospholipids

Fats containing phosphoric acid and nitrogen (lecithin)

Glycolipids

Fatty Acids compounded with CHO, but no N

Derived lipids

Substances from the above derived by hydrolysis

Sterols

Large molecules with alcohols found in nature and combined with fatty acids (cholesterol)

Saturated Fatty Acid

No double bonds between carbons in chains they are tightly packed (like building a wall with bricks), stearic melts at 70oC clog arteries as atherosclerosis

Polyunsaturated Fatty Acid

More than one double bond in the chain because of double bonds PUFA do not pack well

Most common polyunsaturated fats are:

- Oleic
- Linoleic
- Linolenic acid

Oleic melts at (what temp)

26oC

Unsaturated Fats

Have lower melting points, irregular-shaped objects

Fatty Acids

Linear chain of C-H bonds

Fatty Acids

Integral part of triglycerides/phospholipids

Fatty Acids

Store large amounts of energy

Essential Fatty Acids:

Linolenic and Linoleic acid

Fatty Acids

Acquired by diet

Triglycerides

- Composed of 3 fatty acid molecules, which includes glycerol
- Hydrophobic
- Comprises of 95% of fat stored in tissue

Exogenous (triglycerides)

Come from the diet (Plant or animal sources)

Endogenous (triglycerides)

Synthesized by the body

Phospholipids

- Composed of 2 fatty acid molecules
- Amphipathic
- Has both hydrophilic and hydrophobic parts
- Found on surfaces of lipid layers.
- Synthesized in the liver

Cholesterol

Synthesized in animals, plants, our bodies

Functions of Cholesterol

- Promotes fat absorption in intestine via bile acids
- Produces some hormones
- Transforms Vitamin D in the skin
- Component of cell membranes

Exogenous (cholesterol)

Originates in animal products also absorbed via via biliary secretions, intestinal secretions, and turnover of intestinal mucosal cells

Endogenous (cholesterol)

Produced in the liver and intestine from acetyl-CoA

General Structure of Lipoproteins

- Size of the molecule correlates with lipid content
- Composed of both lipids and proteins
- Outer layer of proteins

Outer layer of proteins is called

Apolipoprotein

Five categories of Lipoprotein

1. Chylomicrons
2. VLDL
3. IDL
4. LDL
5. HDL

Chylomicron

Largest and least dense of the lipoproteins

Chylomicron

Lipid-rich transport vessel that carries triglyceride in circulatory system to cells

Appearance of Chylomicron

Creamy layer in samples

VLDL: very low density lipoproteins

Carry triglycerides to cells for energy use and storage Liver-made

Appearance of VLDL (in fasting samples)

turbid

HDL: High density lipoproteins

- Gather excess cholesterol and return them to liver
- Made in liver and intestine

LDL: Low-density lipoproteins

Deliver cholesterol to peripheral cells and liver following triglyceride removal

Function of Apolipoproteins

- Maintain structural integrity
- Maintain structural integrity
- Activator/Inhibitor of various enzymes

Types of Alipoprotein

Apo A-I
Apo B
Apo C
Apo E

Apo A-I

Major protein on HDL

Apo B

Principal protein on LDL, VLDL and chylomicrons ,

Two forms of Apo B

B-100 and B-48

Apo C

Activates lipoprotein lipase (LPL) to break down triglycerides

Apo E

Promotes binding of LDL, VLDL

Three pathways of Lipid Metabolism

1. Lipid absorption
2. Exogenous
3. Endogenous

4th pathway

Reverse cholesterol transport

Reverse cholesterol transport

Maintains cholesterol equilibrium

Lingual lipase

provides a stable interface with aqueous environment of stomach

Pancreatic lipase

major enzyme affecting triglyceride hydrolysis

Colipase

Protein anchoring lipase to the lipid

Lipid esterase

secreted by pancreas, acts on cholestrol esters, activated by bile

Phospholipases

Cleave phospholipids, activated by trypsin

Bile

- They form the spherical structures (micelles) assisting in absorption
- Hydrophobic portion (tails of FA) are located to the inside of the micelle, with heads (hydrophilic portion) to the outside
- They move lipids from the intestinal lumen to the cell surface
- Absorption is by diffusion

Absorption

occurs when micelles contact membranes of the intestinal mucosal

Endogenous Pathway

Transport of hepatic-derived lipids

Reverse Cholesterol Transport Pathway

Mediated by HDL

Specimen Collection for Lipid Analysis

Serum

For fasting specimen (number) of hours is preferred

12

Lipemia

affects assays by affecting absorbance due to refraction of light

True

True or False: Serum lipoprotein concentrations differ between adult men and women

True

True or False: Men and women both show a tendency toward increased total cholesterol, LDL-C, and triglyceride concentrations with age

False

True of False: Women (on average) - lower HDL-C level

Liebermann-Burchard

Classical method

Liebermann-Burchard

- Involved extraction & hydrolysis
- Uses sulfuric & acetic acids

Result of Liebermann-Burchard

formation of green color (proportional to the cholesterol)

Precipitation Reaction

Dextran sulfate or phosphotungstate acid with magnesium chloride precipitates LDL and VLDL lipoproteins

Homogeneous Reaction

Detergents or enzymes binds sites of VLDL and LDL particles. HDL is then left to react with colored products and can be measured

Homogeneous Reaction (disadvantage)

Lacks specificity for HDL

Elevated triglyceride levels exceeds (number)

400 mg/dL

Desirable range for HDL

\> 60 mg/dL

Gray area (HDL range)

40-59 mg/dL

High risk (HDL range)

< 40 mg/dL

Triglyceride Measurement Methods

Enzymatic and Colorimetric

Triglyceride Reference Range
(Recommended)

< 150 mg/dL

Triglyceride Reference Range
(Borderline high)

150-199 mg/dL

Triglyceride Reference Range
(High)

200-499 mg/dL

Triglyceride Reference Range
(Very high)

\> 500 mg/dL

LDL measurement

Friedewald estimation (calculation)

Arteriosclerosis

Stems from the deposition of lipids in artery walls

Hyperlipoproteinemia

Result of malfunctions in the synthesis, transport or catabolism of lipoproteins

Hyperlipoproteinemia

Elevated lipoprotein levels

Hyperlipoproteinemias can be subdivided into:

1. Hypercholesterolemia
2. Hypertriglyceridemia
3. Combined hyperlipidemia with elevations of both cholesterol and triglycerides

Hypercholesterolemia

Linked to heart disease

Familial hypercholesterolemia (FH)

Genetic abnormality that predisposes people to high cholesterol levels, specifically LDL cholesterol

Hypertriglyceridemia

Imbalance between synthesis and clearance of VLDL in circulation

Hypertriglyceridemia

Deficiency of LDL or apo-C ( co-factor for LPL activity)

Causes of Hypertriglyceridemia

- Genetic Abnormalities
- Familial hypertriglyceridemia

Secondary causes of Hypertriglyceridemia

- Hormonal abnormalities in pancreas, adrenals, pituitary
- Diabetes mellitus

Triglycerides are influenced by a number of hormones

- Insulin
- Glucagon
- Pituitary growth hormone
-Adrenocorticotropic hormone (ACTH)
- Thyrotropin Epinephrine
- Norepinephrine

Combined Hyperlipoproteinemia

Presence of elevated levels of serum cholesterol and triglycerides

Combined Hyperlipoproteinemia

- Risk factor for CHD
- Primarily congenital

Hypolipoproteinemia

Low levels of lipoproteins

Two forms of Hypolipoproteinemia

Hypoalphalipoproteinemia and Hypobetalipoproteinemia

Hypoalphalipoproteinemia

-Decrease in circulating HDL (< 40 mg/dL)- Lack of hypertriglyceridemia
- Due to a genetic defect

Hypobetalipoproteinemia

low levels of LDL cholesterol