Lipids 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.
· 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