Question

Discuss prevention of futile cycles between fatty acid synthesis and beta-oxidation in liver and include transporter system (4 key regulatory steps & regulation) between cytosol and mitochondria B) What are the major differences in the regulation beta-oxidation in Muscle compared to liver?

Answer 1

Answer:

• A futile cycle is a substrate cycle in which two metabolic pathways occur side by side but in opposite directions and dissipate heat energy.
• There is no overall effect produced.

Mitochondrial matrix is the site of fatty acid oxidation.

• To initiate fatty acid synthesis, fatty acids are first activated and transported across the mitochondrial membrane.
• the inner membrane of mitochondria is impermeable to fatty acids and reqiures carnitine carrier system for their transport across the membrane.
• Transport involves fatty acid transporters present on the mitochondrial membrane,

1.fatty acid translocase (FAT/CD36) -a tissue-specific transport protein

2.FABP- fatty acid binding protein (bound to plasma membrane)

• first, acyl CoA binds to carnitine via carnitine acyltransferase
• It is prevented to move to the mitochondrial matrix for beta-oxidation by malonyl-CoA (inhibitor of carnitine acyltransferase and intermediate between fatty acid synthesis).
• Malonyl CoA inhibits the action of carnitine acyltransferase and thus avoiding a futile cycle (between fatty acid synthesis and beta-oxidation).
• secondly, CPT1 (Carnitine palmitoyltransferase-1) flips fatty acid moiety of acylcarnitine across the membrane through carnitine translocase.
• Thirdly, carnitine acyltransferase (CPT-2) converts acylcarnitine to acyl CoA. Carnitine released and move back to the cytosol and acyl CoA enters fatty acid beta-oxidation pathway.

outside cell Inside cell, fatty aud falty and transporter fatty and I FACS Falty arylcoA - Augl canet Augl canetine canetine Top ICAT I augl Camitine Carnitine falty ayl CoAE poxidation Acetyl con TCA cycle e NADHIFADHI {Electron Transport chatule

• In muscles, fatty acids act as a substrate for oxidation while in liver they are involved in secretion of very low lipid density lipoprotein via re-esterification within the endoplasmic reticulum.

$\rightarrow$Beta oxidation regulation of fatty acid in muscles:

• fatty acids present in muscles are used for oxidation. Hormone-sensitive lipase-HSL is the key regulating enzyme in muscles and is activated on muscle contraction.
• fatty acids from muscle triglycerides are activated after entering the mitochondria. Muscle lipolysis is less sensitive than liver lipolysis.
• In liver, fatty acids enter hepatocytes into the mitochondrial matrix for fatty acyl oxidation or can act as a substrate for lipoproteins synthesis.
• This regulatory point is determined by entry to the matrix of mitochondria by the CPT-1 enzyme.

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