Download Lipid Metabolism

Lipid Metabolism By Dr. Mohammad
1. Fatty acid synthesis is low when glucose is low.
 In fasting state and high-diet fat stimulate secretion of anti-insulin hormones which
increases the rate of lipolysis in adipose tissues and increases the release and oxidation of
free fatty acid.
 Thus ,acetyl-coA carboxylase and fatty acid synthase which are responsible for fatty acid
synthesis are inhibited when glucose is low.
2.Severe uncontrolled D.M. is complicated by ketosis, hypercholesterolemia, and fatty liver.
 Severe uncontrolled D.M is complicated by Increased oxidation of FFA increases ketogenesis
in liver may lead to ketogenesis, hypercholestremia result from increased synthesis of TAG in
liver and decreased clearance of plasma lipoproteins,fatty liver due to over mobilization of
depot fat.
3.Excess ethanol intake (alcoholism ) cause hypoglycemia and fatty liver.
 As ethanol intake leads to increase NADH/NAD+ ratio , it will lead to inhibiton
gluconeogenesis due to reduction of oxaloacetate to malate(in cytosol),thus results in
hypoglycemia.
 Inhibition of fatty acid oxidation and increases fatty acid synthesis and esterification for
triacylglycerol synthesis resulting in fatty liver.
4.During fasting cholesterol synthesis is low.
 HMG-CoA reductase is the key enzyme for cholesterol synthesis. It is present in two forms
active (dephosphorylated) and inactive (phosphorylated).
 The activity of the enzyme is regulated by cAMP dependent enzyme system, increased by
carbohydrate feeding and by insulin and decreased by fasting and glucagon.
5. Ethanol intake aggravates gouty status.
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Ethanol intake will lead to increase NADH/NAD ratio .
This will cause the conversion of pyruvate to lactate ,results in hyperlacticacidemia which in
turn decrease the capacity of the kidney to excrete uric acid.
This leads to increase uric acid in blood (hyperuricemia).That’s why by drinking alcohol, it
will aggravates gout.
6. Fate of HMG-CoA in liver mitochondria differs from that in the cytosol
 Fate of HMG- CoA :
 In liver mitochondria : as a substrate in ketone bodies metabolism.
 HMG-CoA undergoes oxidation reaction in liver mitochondria to form acetone and
3-hydroxybutyrate.
 The enzymes used are HMG-CoA synthase and HMG-CoA lyase.
 In cytosol : as a substrate in cholesterol metabolism. HMG-CoA is found in cholesterol
synthesis. The enzyme used is HMG-CoA synthase
Lipid metabolism
7.Over feeding of carbohydrate causes fatty liver.
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Stimulates lipogenesis, as increase glucose in blood, increase pyruvate, increase active
acetate, therefore the availability of substrate for lipogenesis increase thus stimulate
lipogenesis
Carbohydrates feeding stimulates release of insulin,insulin decreases lipolysis
total effect of increase lipogenesis and decrease lipolysis may lead to fatty liver
8.Hyperthyroidism cause hypocholesterolemia.
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Thyroxine stimulates conversion of cholesterol to bile acid.
Therefore, increase thyroxine will lead to decrease of cholesterol in blood
(hypocholesterolemia).
9.Aspirin is used to prevent platelet aggregation.
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Aspirin is non stroidal anti-inflammatory drug that inhibit cyclooxygenase pathway by
acetylation.
It will inhibit prostaglandin synthase which catalyze synthesis of prostaglandin, prostacyclin,
and thromboxane.
Thromboxane is responsible for platelet aggregation.
10.Obstructive jaundice cause hypercholesterolemia.
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About 1gm of cholesterol is excreted daily, 50% in the form of bile acid and 50% in the form
of cholesterol.
Bile acid are excreted in bile through bile duct. However, in obstructive jaundice, there is
blockage of common bile duct (stone or tumor).
Hence, there is a decrease in excretion of cholestrol and bile acids.
This lead to accumulation of cholesterol and bile acid in liver. The liver provide plasma
cholesterol.
11.HDL promotes the prevention of coronary artery risk disease.
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HDL are endocytosed by the liver cells , where CE are hydrolyzed . The free cholesterol
released either:
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Repacked in to lipoprotein
Converted to bile acid OR
Secreted in bile.
This will decrease the cholesterol level in blood, reducing the risk of deposition of
cholesterol in arterial wall, as it removes cholesterol from tissue to liver. (reverse
cholesterol transport)
Thus, high level of HDL protect against atherosclerosis, which prevent the coronary artery
risk disease. *atherosclerosis is depositon of lipid especially cholesterol and cholesterol
ester in arterial wall.
12. LONG CHAIN ACYL-COA INHIBITS FATTY ACID SYNTHESIS.
Free fatty acid will be converted to the acyl-CoA by the reaction of Acyl-CoA synthetase. The
long chain acyl-CoA produces metabolic feedback inhibition of the acetyl-CoA carboxylase which
is the key enzyme for the fatty acids synthesis.
13. STATINS (LIKE LOVASTATIN) AND THYROID HORMONES (AS IN HYPERTHYROIDISM)
REDUCE PLASMA CHOLESTEROL LEVEL.
Thyroxine stimulates conversion of cholesterol to bile acids. In hyperthyroidism, more
cholesterol is converted to bile acids, therefore plasma cholesterol level is reduces.
14. METHYL DONORS ARE LIPOTROPIC FACTORS.
Lipotropic factors are substances needed for synthesis of plasma lipoproteins. One of these
factors is choline and methyl donors or compounds. Methyl donors such as glycine betaine, folic
acid and vitamin B12 needed for the synthesis of methyl group, which required for methylation of
ethanolamine to form choline.
Dr. Mohammad A. R. Ismaiel
College of science for Women /Babylon University