lipid transport

• chylomicrons leave the enterocyte and enter the lymphatic system and then drain into the venous system
• MCFA and SCFA are not part of the chylomicron, they enter blood directly from the enterocytes, bind to albumin
• lipoprotein lipase (LPL): stimulates lipolysis, the breakdown of TG and FA and glycerol, which can enter the cell
• Muscle: FA used as source of energy or combined with glycerol to form an intramuscular triglycerides (IMTG)
• Adipocyte: FA combine with glycerol to form TG
• Chylomicron remnant: sent back to liver, contain dietary CE and fat-soluble vitamins
• VLDL: transport dietary FA, could be from fructose in the liver (chylomicrons do not carry fructose derived FA)
• LDL: deliver cholesterol to the body
• HDL: pick up excess CE from nonliver cells and deliver to liver
• Synthesis of VLDL: postprandial (also in fasted) in liver, in ER lumen, begins with synthesis of ApoB-100 and the MTTP, then mature VLDL
• lipoprotein lipase recognizes Apo-C2 protein on surface of VLDL, FA are then uptaken by muscles or adipocyte
• lipid storage: adipose tissue during fed state promotes FA uptake by insulin-mediated increase of LPL activity
• VLDL and CM acquire Apo-C2 from HDL in circulation
• Cholesterol is a steroid lipid and is synthesized in the body in liver, SI, adrenal cortex (steroid hormones) and the gonads
• CE from the diet is much lower than synthesized
• Lipoproteins transport endogenous CE and CMs transport dietary CE
• Sex hormones: synthesized from cholesterol (estrogens, progesterone, testosterone)
• Glucocorticoids (cortisol): synthesized from CE, adrenal cortex, promotes gluconeogensis
• Mineralocorticoids (aldosterone): synthesized from CE, adrenal cortex, promote Na reabsorption
• Bile acids: synthesized from CE, in liver
• Isoprenoids: synthesized from CE precursors, vitamin D, isoprene base is from CE
• CE synthesis: three acetyl-CoA make HMG-CoA
• CE Synthesis: HMG-CoA is reduced by HMG-CoA reductase to make mevalonate, this is a key regulatory step and is targeted by statins
• high levels of CE lead to HMGCR to get shuttled out of the ER membrane and broken down
• HMGCR: active in dephosphorylated form, inactive in phosphorylated form
• Dyslipidemia: low HDL, high LDL, high total-C, high TG. want high HDL because it shuttles CE out of cells