T1 L15: Lipid metabolism and pathways

• 2 major metabolic pathways of triglyceride metabolism?

  1. Oxidation of fatty acids in mitochondria to release ATP
  2. Synthesis of fatty acids from Acetyl-CoA
• Beta-oxidation?

  removal of glycerol, oxidation of long chain fatty acids to 2-carbon fragments in the form of Acetyl-CoA
• Where does beta-oxidation of fatty acids occur?

  mitochondria
• Lipogenesis?


  fatty acid synthesis
• Where does lipogenesis mainly occur?

  liver and adipocytes
• Acetyl CoA is normally in the mitochondria, so needs to be moved to cytosol via the citrate malate cycle for lipogenesis.
• Summary of fatty acid biosynthesis?

  citrate -> Acetyl CoA -> carboxylation (rate-limiting) -> Malonyl CoA

  Malonyl CoA + Acetyl CoA -> bind to fatty acid synthase

  Fatty acid synthase -> builds the fatty acid molecule up to 16C

  >16C fatty acid molecule requires additional fatty acid elongase enzyme .
• What is the rate-limiting step of fatty acid synthesis?

  formation of malonyl CoA from acetyl CoA, catalysed by acetyl CoA carboxylase

  This step allows control of fatty acid synthesis

  Is inhibited by palmitoyl CoA

  increased by citrate

  also regulated by glucagon + insulin
• Physiological roles of cholesterol?

  component of membranes

  precursor of steroid hormones

  source of bile acids
• Bile acids are polar derivatives of cholesterol.
• Bile acids aid in?

  lipid digestion

  lipid absorption

  cholesterol excretion
• Cholesterol is synthesised from?

  acetyl CoA
• Cholesterol is eliminated as?

  bile acids
• Cholesterol structure?

  amphipathic lipid (hydrophobic and hydrophilic portions)
• What enzymes catalyse formation of cholesterol esters?(cholesterol -> ester)

  Acyl-CoA cholesterol acyltransferase (ACAT)
• What enzyme catalyses the conversion of esters back to free cholesterol? (ester -> free cholesterol)

  NCEH
• Cholesterol biosynthesis route?

  Acetyl CoA -> HMG-CoA -- (HMG-CoA Reductase)--> Mevalonate -> Squalene -> Cholesterol
• Rate determining step for cholesterol biosynthesis?

  HMG-CoA reductase
• Target site for statin drugs?

  HMG-CoA reductase (rate-determining step for cholesterol biosynthesis)
• Transport of short-chain fatty acids in blood via?

  blood proteins eg albumin
• Bulk transport of neutral lipids (insoluble in water) via?

  Lipoproteins - special carrier proteins
• VLDL?

  very low density lipoproteins
• IDL?

  intermediate density lipoproteins
• LDL?

  low density lipoproteins
• HDL?

  high density lipoproteins
• VLDL transport what?

  endogenous triglycerides

  cholesterol
• LDL's transport what?

  cholesterol from liver to tissue
• HDL's transport what?

  cholesterol from tissues to liver
• Chylomicrons transport what?

  dietary triglycerides to muscles and adipose tissue

  dietary cholesterol to liver
• Chylomicrons and VLDL particles give up triglycerides to tissues by the action of what enzymes?

  tissue-bound lipases
• Liver recognises remnants of lipids by their what content?

  ApoE content
• What of LDL particles is recognised by cell-surface LDL receptors (LDLRs)?

  ApoB100
• Uptake of cholesterol results in decrease in what synthesis?

  cholesterol and LDLR
• What happens as a response to low cholesterol in terms of receptors?

  expression of LDL receptors increased
• What results in LDL receptor degradation?

  PCSK9 binding to LDL receptor