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Regulation of Lipogenesis vs. Lipolysis

BIOCHM-3$YRKA

In mammalian adipocytes, fatty acid biosynthesis (lipogenesis) occurs in the cytosol in a process similar to the reverse of $\beta$-oxidation (lipolysis), which takes place in the mitochondrion (see simplified biochemical schematic below). These two pathways need to be regulated relative to the energy demands of the organism at several levels.

MetabolicElizabeth. Inhibition of Glucose by Fatty Acid Oxidation. Wikimedia Commons, 6 Dec. 2013. Web. 26 July 2016. (Modified by M. Rumpho-Kennedy).

A key regulatory and the first committed step of fatty acid biosynthesis is catalyzed by the enzyme acetyl-CoA carboxylase (ACC) producing malonyl-CoA. ACC is highly regulated by allosteric and hormonal effectors, balancing the needs of the cell for lipogenesis vs. lipolysis. Metabolic effectors include citrate, long chain fatty acyl-CoA (LCFAcyl-CoA) molecules, and malonyl-CoA.

ACC is also regulated by covalent modification; Ser phosphorylation inactivates the enzyme. By influencing the phosphorylation state of ACC, glucagon, epinephrine (adrenalin) and insulin influence lipogenesis vs. lipolysis.

Examine the biochemistry of lipogenesis vs. lipolysis in the above schematic relative to the regulatory information provided above.

Then, identify ALL of the following statements which CORRECTLY describe the impact of a particular effector on these processes.

A

High concentrations of citrate likely stimulate ACC activity and lipogenesis.

B

High concentrations of long chain fatty acyl-CoA (LCFAcyl-CoA) molecules likely stimulate ACC and lipogenesis.

C

Elevated glucagon (peptide hormone, stimulates glucose production) levels likely promote phosphorylation of ACC, inhibiting the enzyme and leading to increased lipolysis.

D

Elevated insulin levels likely promote dephosphorylation and thus activation of ACC activity leading to increased lipolysis.

E

Malonyl-CoA inhibits carnitine palmitoyl transferase I (CPT-1; see schematic) likely stimulating lipogenesis and inhibiting lipolysis.