Regulation of Fatty Acid Synthesis | Short & Long term

One enzyme decides whether your cell makes fat: learn how acetyl CoA carboxylase is switched on and off, and finally stop mixing up AMPK and PKA. Learning Outcome By the end of this video you will be able to explain how acetyl CoA carboxylase is regulated in the short term (allosterically and by covalent modification) and in the long term (ChREBP and SREBP-1c), and link it to insulin, glucagon, and the fed and fasting states. Download PDF Note: https://drive.google.com/file/d/1A4DE... Playlist Navigation Lipid Metabolism Playlist:    • Lipid Metabolism | Fat Metabolism   Previous video:    • Fatty Acid Synthase Complex with mnemonics...   Next:    • Fatty Acid Elongation: SER vs Mitochondria...   Timestamp 00:00 Introduction 00:35 Overview of fatty acid synthesis (ACC, fatty acid synthase, palmitate, acyl CoA) 02:38 Short-term regulation: allosteric (protomer and polymer forms) 05:04 Short-term regulation: covalent modification (AMPK, PKA, protein phosphatase) 08:03 Long-term regulation: ChREBP and SREBP-1c 09:16 Recap of regulation of fatty acid synthesis Main Description Fatty acid synthesis is a heavy, energy-consuming process, so the cell must switch it on when energy and carbohydrate are plentiful and switch it off when they are scarce. This video explains how the cell makes that decision, which enzyme is the target, and which signals control it. We begin with a quick overview: acetyl CoA is converted to malonyl CoA by acetyl CoA carboxylase (ACC), the fatty acid synthase complex builds the fatty acid (mostly palmitate), and the fatty acid is activated to acyl CoA (palmitoyl CoA for palmitate). Because acetyl CoA is generated in the mitochondria and cannot cross the membrane, it leaves as citrate through the tricarboxylate transporter and is converted back to acetyl CoA in the cytosol. ACC catalyses the rate limiting and committed step, so it is the main regulatory target. Short-term regulation (seconds to minutes) is allosteric and covalent. Allosterically, ACC exists as an inactive protomer and an active polymer: citrate stimulates polymer formation (feed forward activation, and a high energy signal in the cytosol), whereas acyl CoA promotes disaggregation (feedback inhibition) and also inhibits the transporter. By covalent modification, dephosphorylated ACC is active and phosphorylated ACC is inactive. AMP dependent protein kinase (AMPK) phosphorylates ACC and is stimulated by AMP, and by glucagon and epinephrine through cAMP, cAMP dependent protein kinase (PKA) and AMPK kinase. Insulin stimulates protein phosphatase, which dephosphorylates and activates ACC. Long-term regulation (hours to days) changes the amount of ACC: a carbohydrate rich diet stimulates ChREBP, and the resulting insulin release stimulates SREBP-1c; both are transcription factors that increase transcription of the ACC gene. This ties directly to insulin, glucagon, and the fed and fasting states. Study Resources Mentioned Key diagrams: overview of fatty acid synthesis with the citrate shuttle; ACC protomer and polymer forms; phosphorylated and dephosphorylated ACC with the AMPK pathway; gene to mRNA to ACC protein with ChREBP and SREBP-1c. Memory techniques used: labelling citrate as feed forward activation and acyl CoA as feedback inhibition; the contrast between cAMP dependent protein kinase (PKA) and AMP dependent protein kinase (AMPK); thinking of cytosolic citrate as a high energy signal; a closing recap of short-term and long-term regulation. Related topics to review: the full pathway of fatty acid synthesis and the fatty acid synthase complex; regulation of the TCA cycle by energy status; insulin and glucagon signalling in the fed and fasting states. Disclaimer This video is for educational purposes only. Always refer to your official curriculum and faculty for final exam preparation. The content of this video is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider. No video can supersede the opinion of an experienced and licensed healthcare provider. #RegulationOfFattyAcidSynthesis #FattyAcidSynthesis #AcetylCoACarboxylase #Lipogenesis #Biochemistry #MBBS #AwesomeBiochemistry