Metabolism

Master answer

• Fat
  • triglycerides -> hydrolysed to FFAs & glycerol
  • transported to tissues
  • glycerol -> glycerol-3-phosphate & enters glycolytic pathway
  • FFA’s transported to mitochondria by carnitine carrier -> degraded to ACoA (beta oxidation) -> enters the citric acid cycle.
• essential fatty acids = linolenic, linoleic & arachidonic acid
• used in the production of leukotrienes, prostaglandins, prostacyclin
• Main Components of Dietary Fat
  • Fatty acids: Acylglycerides (esters of glycerol+FA), Phospholipids (2FA+glycerol+Phosphate group)
  • Non Glyceride Components: Vitamin E, Carotenoids, Vitamins A & D
  • Other components: Sterols, Methylsterols and trierpene alcohols, Squalene, Oryzanols

Lipid Transport

• Digestion: splitting TGs into monoglycerides + FFAs
• Absorption: inside intestinal epithelial cells; resynthesis into TGs + packaged as chylomicrons → circulate in venous system for transport to liver + adipose tissue
• Storage: lipoprotein lipase hydrolyses TGs + phospholipids in chylomicrons → FFAs + glycerol → diffuse into fat (adipose cells) + liver (hepatocytes) → resynthesises as TGs inside cells for storage
• Transport: via synthesised lipoproteins which contain TGs, cholesterol, phospholipids, and protein; formed in liver; transport + deposit lipid components in blood + peripheral tissues. E.g. of lipoproteins – chylomicron, VLDL, LDL, HDL
• Synthesis: liver can synthesise TGs from carbohydrates; cholesterol + phospholipids from FFAs
• Mobilisation: stored fat is hydrolysed by hormone sensitive lipase → released + transported as glycerol + FFAs → ionised and carried on albumin. Activation by starvation

Lipid Metabolism

• Glycerol can be converted to Glucose by the liver
• Free Fatty Acids:
  • transported from ECF to ICF by fatty acid transporter
    • FACoA synthase in cytosol makes FACoA
    • Converted to Acyl carnitine by CPT1 and transported into mitochondrion
    • Converted back to FACoA by CPT2
  • β-oxidation of FFA (Phase 1 reaction)
    • FFA derived from diet and lipolysis of fat stores (via lipoprotein transport) is partially oxidised in mitochondrial matrix by removal of 2-C moieties (as acetyl CoA) at a time
    • Lipolysis of fat stores is ↑ by GH, GC and Adr (stimulates TAG lipase)
  • TCA cycle (Phase 2 reaction)
    • occurs in mitochondrial matrix under aerobic conditions only
    • → consumes breakdown products of glucose (as acetyl CoA), FFA (as acetyl CoA) and a.a (as TCA intermediates – α-ketoglutarate, oxaloacetate, fumarate, succinyl CoA) to produce
    • → (i) 2x CO2, (ii) 1x ATP, (iii) 3x NADH + H+ / 1x FADH2 – per acetyl-CoA metabolised
    • TCA cycle stimulated by ↓ NADH/NAD+ ratio (as NADH inhibits dehydrogenase enzymes of the cycle)
  • Electron Transport Chain (Phase 3 reaction)
    • Electrons donated to ETC by NADH/FADH2 → passed along series of cytochromes (along inside surface of inner mitochondrial membrane) down its energy gradient until they are accepted by O2 at the end (via cytochrome a)
• Transported as chylomicrons to Adipocytes
  • o Degraded by Lipoprotein lipase to FFAs and Glycerol (Heparin is a cofactor)
  • o FFAs and Glycerol transported into Adipocyte
  • o Converted back to Triglycerides for storage.
• Ketone body metabolism:
  • Ketone bodies (acetoacetate, β-OH-butyrate) are formed in liver only when there is extra acetyl CoA formed by β-oxidation of excess FFA (2° to ↑ lipolysis by GH, GC, Adr)
  • Ketone bodies are released from liver → utilised peripherally by skeletal muscle, heart, kidney (and brain/nervous tissue during starvation)

Bianca / Kerr 2016

Answer by Bianca, Kerr