Objectives - Mans
Transcript of Objectives - Mans
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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.
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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
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Type VI, hyperalphalipoproteinemia
characterized by increased HDL & hypercholesterolemia It occurs during estrogen therapy.
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Hypolipoproteinemias
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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
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2. Hypobetalipoproteinemia
Familial disease
Caused by decreased formation of
the apo-B100 by the liver
decreased formation of VLDL & LDL
Decreased plasma lipids
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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
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• 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
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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
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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)
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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
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(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
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(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
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(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
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Oxidation of Fatty Acids
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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
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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
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FAs to be oxidized must be entered the following 2 steps
1-Activation of FA 2- Transport of acyl
COA to mitochondria
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RCOOH Acyl COA synthetase
RCO~SCOA
AMP+P~P COASH
2Pi + E
Pyrophosphatase
1-FA activation
ATP
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2- Transport of acyl COA to mitochondria:
Role of carnitine in the transport of LCFA through the inner mithochochondrial membrane
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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
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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
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Steps of β-Oxidation of
FAs
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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
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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)
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Summary
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Questions
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