Objectives

By the end of lecture the student should:

Mention types, causes, and manifestation of lipoprotein disorders.

Illustrate enzymes involved in lipid transport.

Discuss oxidation of fatty acids.

Type V Hyperchylomicronemia & Hyperprebetalipoproteinemia

Characterized by increased chylomicrons and VLDL increase triacylglycerols & some what cholesterol The plasma is turbid The cause of disease is unknown, but may be due to increase formation of apo- B. it is usually associated with obesity and glucose hypotolerance

Type VI, hyperalphalipoproteinemia

characterized by increased HDL & hypercholesterolemia It occurs during estrogen therapy.

Hypolipoproteinemias

Hypolipoproteinemias

1. Abetalipoproteinemia

familial disease.

Caused by failure of liver & intestine to

synthesize apo B absence of

chylomicrons, VLDL & LDL from blood

marked decrease in plasma lipids

The intestine fails to absorb

triacylglycerols fatty diarrhea

The liver fails to mobilize fats to the blood

fatty liver

2. Hypobetalipoproteinemia

Familial disease

Caused by decreased formation of

the apo-B100 by the liver

decreased formation of VLDL & LDL

Decreased plasma lipids

3. Alphalipoprotein deficiency

• Familial disease

• Caused by failure of the liver to

synthesis apo-A

• Cholesterol esters accumulate in

tissues (Tangiers disease)

• Plasma triacylglycerols are increased

due to deficiency of apo C-II the activator

of lipoproteins lipase

• HDL is absent in Tangier disease

** There is an important relationship

between atherosclerosis and HDL:

Decreased HDL is associated with

atherosclerosis

Increased HDL represents protection

against atherosclerosis

Increased LDL/HDL ratio predispose to

atherosclerosis

Decreased LDL/ HDL ratio good sign

Lecithin-cholesterol acyl transferase deficiency:

Familial disease

Abnormal plasma HDL, LDL and VLDL are

present

Cholesterol + Lecithin Cholesteol ester + Lysolecithin (From tissues) (From HDL) (To HDL) (To Tissues)

LCAT – apo A1

Enzymes Involved in Lipid Transport

(1) LCAT:

Transfer acyl group from lecithin (HDL) to

cholesterol forming cholesterol ester &

lysolecithin

Site: plasma

Activated by apo A1 (HDL)

Enzymes Involved in Lipid Transport

(2) Lipoprotein Lipase:

Site: wall of blood capillaries in all tissues

except liver and brain.

Attached to endothelial cells by heparin

sulphate

It hydrolyses triglycerides present in

chylomicrons & VLDL

(3) Hepatic Lipase:

Site: endothelial cells of the liver,

Similar action to lipoprotein lipase but it is

more specific in hydrolyzing TG in smaller

particles as VLDL reminants (IDL) &

chylomicrons reminants.

Enzymes Involved in Lipid Transport

(4) Mobilizing Lipase

(Hormone sensitive

triglyceride lipase):

Site: adipose tissue

cells,

controls the release

of FA from adipose

tissue to plasma.

Enzymes Involved in Lipid Transport

(5) (HMG COA) reductase enzyme

Control cholesterol biosynthesis (Key enzyme).

Activity is controlled by amount of cholesterol

cells which in turn largely depends on

cholesterol uptake from the blood.

Enzymes Involved in Lipid Transport

Oxidation of Fatty Acids

Oxidation of Fatty Acids

1- β-Oxidation (knoop’s oxidation):

Removal of 2 carbon fragment at a time form

Acyl CoA (active FA).

The 2 carbon removed as acetyl CoA.

It occurs in many tissues including liver,

kidney & heart

Site of fatty acids β-Oxidation:

doesn’t occur in the brain as fatty acid

can’t be taken up by that organ

The mitochondria are the principle site

FAs to be oxidized must be entered the following 2 steps

1-Activation of FA 2- Transport of acyl

COA to mitochondria

RCOOH Acyl COA synthetase

RCO~SCOA

AMP+P~P COASH

2Pi + E

Pyrophosphatase

1-FA activation

ATP

2- Transport of acyl COA to mitochondria:

Role of carnitine in the transport of LCFA through the inner mithochochondrial membrane

1- Transport long chain acyl COA across mitochondrial

membrane into the mitochondria so it increases the rate

of oxidation of LCFA

2- Transport acetyl-CoA from mitochondria to cytoplasm

So it stimulates fatty acid synthesis

Functions of carnitine

α

Cβ

O ~ S – CoA β

H3C

Palmitoyl-CoA

CoA-SH

α

CO ~ S – CoA β

H3C

Successive removal of C2 units

CO ~ S – CoA

Acetyl-CoA

+

8CH3 – CO ~ S – CoA

Acetyl-CoA

CoA-SH

β

Palmitoyl-CoA

α

β

H3C

H3C

α

CH3 – CO ~ S –CoA

+ β

8CH3 – CO ~ S – CoA

Acetyl-CoA

Steps of β-Oxidation of

FAs

Energetics of FA oxidation

Palmitic (16C):

β-oxidation of palmitic acid will be repeated 7

cycles producing 8 molecules of acetyl COA

In each cycle FADH2 and NADH+H+ is

produced & transported to respiratory chain

FADH2 ------------------ 2 ATP

NADH+H+ ------------- 3 ATP

So 7 cycles 5X7=35 ATP

each acetyl-CoA which is oxidized in citric

cycle gives 12 ATP (8X 12= 96 ATP)

2 ATP is utilized in the activation of fatty acid

(it occurs once)

Energy gain = Energy produced-Energy utilized

= 35 ATP+ 96 ATP-2 ATP= 129 ATP

Calculation of Energetics of any FA Oxidation:

[(N/2-1)X 5 ATP]+[N/2X12 ATP]-2ATP

(N= Number of carbons of fatty acid)

Summary

Questions