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.