Long chain fatty acids penetrates in the inner mitochondrial membrane through
(Carnitine derivatives) (184-lIarper 28th)* Long chain fatty; acids penetrate the inner mitochondrial membrane as carnitine derivatives (184-Harper 28th)* The inner mitochondrial membrane is impermeable to fatty acids. A specialized carnitine carrier system (Carnitine shuttle) operates to transport activated fatty acids from cytosol to the mitochondria (288.U. Satyanarayan 3rd)* Inhibitor of carnitine shuttle is Malonyl CoATransport of long chain fatty acids (LCFA) in to mitochondriaAfter a LCFA enters a cell, it is converted in the cytosol to its CoA derivative by long chain fatty acyl CoA synthetase (thiokinase) an enzyme of the outer mitochondrial membrane. Because b-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across inner mitochondrial membrane which is impermeable to CoA. Therefore a specialized carrier transports the long chain acyl group from the cytsol into mitochondrial matrix. This carrier is carnitine and this rate limiting transport process is called the carnitine shuttle* Zellweger syndrome - is caused by the absence of peroxisomes in tissues as a result, the long chain fatty acids can not be oxidasedEntry of short and median chain fatty acids into the mitochondria (192-Lippincotf s 4th)* Fatty acids shorter than 12 carbons can cross the inner mitochondrial membrane without the aid of carnitine or the CPT system {carnitine palmitoyl transferase) once inside the mitochondria, they are activated to their CoA derivatives by matrix enzymes and are oxidized [Note- median chain fatty acids are plendiful in human milk. Because their oxidation is not dependent on CPT-1, it is not subject to inhibition by malonyl CoA)* Medium chain fatty acyl CoA dehydrogenase (MCAD) deficiency is one of the most common inborn errors of metabolism it causes decrease in fatty acid oxidation, resulting in hypoketonemia and severe hypoglycemiaImportant Points* Hormone sensitive lipase activity is inhibited by the hormone Insulin* Two final products in P-oxidation of odd chain fatty acids are- Acetyl coA andpropionyl coA* Maximum absorption of short chain fatty acids produced by bacteria occurs in the colon*** Absorption of long chain FA is greatest in the upper parts of the small intestine* Normal fecal fat excretion is less than 6gm/day more than 6 gm 24 hours indicates malabsorptions* Steatorrhea is defined as stool fat exceeding 7 gm/day* Sudan III is the best for screening but gold standard is quantitative estimation offecal fat* Esterified FA in the form of triacylglycerols serve as the major reserve of the body* Trans Fatty Acids - Classified as unsaturated fatty acids but behave more like saturated fatty acids in the body that is they elevate serum LDL and they increase the risk of CHD** & DM* TFA are formed during the hydrogenation of liquid vegetable oils** Fried foods*** Docosahexaenoid acid (DHA) is particularly needed for development of brain and retina and is supplied via the placenta and milk***
Free fatty acids
Carnitine derivatives
Thiokinase
Malonyl CoA
Lipids