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Home » GATE Study Material » Pharmaceutical Science » Bio Chemistry » Lipid Metabolism

Lipid Metabolism

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Lipid Metabolism

Lipid Metabolism

Lipid digestion and absorption


Lipids play an important role in cell structure and metabolism. TAGs are the major storage form of energy. Cholesterol is a component of cell membranes and precursor of steroid hormones. Lipid digestion occurs at lipid water interfaces since TAG is insoluble in water and digestive enzymes are water soluble. Lipids are digested and absorbed with the help of bile salts. Products of lipid digestion aggregate to form mixed micelles and are absorbed into the small intestine. Lipids are transported in the form of lipoproteins.

Fatty acid oxidation


Fatty acids have to be activated prior to their entry into mitochondrial matrix where the enzymes of β-oxidation of fatty acids are located. Activated fatty acids are then transported from cytosol to the mitochondrial matrix with the help of carnitine transporter. Total net yield of ATP per molecule of palmitic acid is 129. Similarly oxidation of unsaturated and odd chain fatty acids also take place with additional reactions. Β-oxidation in peroxisomes involves three enzymatic reactions. Minor pathways of oxidation such as α-oxidation of branched chain fatty acids and ω-oxidation of medium and long chain fatty acids in microsomes do take place in our body.
 
Ketone body metabolism
Ketone bodies are acetoacetate, β-hydroxy butyrate and acetone. Ketone bodies are synthesized in the liver but they are utilized by extra hepatic tissues as fuels. Ketone bodies are accumulated in the blood if the rate of synthesis exceeds the ability of extra hepatic tissues to utilize them. This leads to excess ketone bodies in blood, excretion of ketone bodies in urine and smell of acetone in breath. All these three together are known as ketosis. In uncontrolled diabetes mellitus and starvation, ketone bodies are formed.

 

Fatty acid biosynthesis


The enzymes of synthesis are located in the cytoplasm. Acetyl CoA is the source of carbon units and NADPH provides reducing equivalents. ATP is the supplier of energy. Synthesis is not the reversal of oxidation. Dimer of fatty acid synthase takes part in fatty acid synthesis. TAGs are synthesized from fatty acyl CoA and glycerol 3-phosphate or dihydroxy acetone phosphate. TAG gets deposited in adipose tissue.

 

Cholesterol biosynthesis


80% of endogenous cholesterol is formed in the liver. Enzymes involved in the synthesis are partly located in the endoplasmic reticulum and partly in the cytoplasm. Acetyl CoA is the precursor. HMG CoA, mevalonate, isopentenyl pyrophosphate, squalene are some of the important intermediate compounds formed during cholesterol synthesis. Cholesterol is transported in lipoprotein complexes. Elevation of lipids in blood leads to the deposition of cholesterol on the arterial walls leading to atherosclerosis.

 

Eicosanoids


Prostaglandins are synthesized from arachidonic acid. Cycloxygenase enzyme catalyzes the reaction in which C20 fatty acid is converted to prostaglandins. Leukotrienes are also derived from arachidonic acid.

 

Synthesis of phospholipids and sphingolipids


Glycerol is the starting material in the synthesis of glycerophospholipids. CDP-diacylglycerol is the activated intermediate of this pathway. Sphingolipids are synthesized from palmitoyl CoA and serine, initially to form ceramide. Sphingomyelins and glycolipids are synthesized from ceramide. Various sphingolipids storage diseases are resulted due to hereditary absence of hydrolytic enzymes.



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