Lipids (fats and oils) are a high-energy source yielding twice the energy per gram of protein and carbohydrate. Around 30% of calorific intake by humans is currently recommended, as an upper limit, to be in the form of lipid. Lipids are utilised as a fuel during fasting, starvation and stress, when fatty acids are mobilised from the storage lipid triacyglycerol, stored in adipose tissue, and are metabolised by tissues such as skeletal muscle and liver, but not by the brain or erythrocytes. Fatty acid oxidation yields energy and acetylCoA (acetylCoA), which feeds into the tricarboxylic acid (TCA) cycle or in the liver is used to make ketone bodies.
Lipolysis
Low blood glucose concentrations trigger the release of glucagon by the pancreas, which in turn activates a hormone-sensitive lipase in adipose cells (adipocytes), which in turn hydrolyses triacyglycerol to free fatty acids and glycerol (Figure 11.1). Glucagon binding to its cell-surface receptor leads to an increase in intracellular cAMP, which activates protein kinase A, which phosphorylates and activates hormone-sensitive lipase. The resulting free fatty acids are released to the circulation, bound to the plasma protein albumin, from where they can be taken up by other tissues. Fatty acids freely pass the plasma membrane into the cytosol but cannot cross the blood–brain barrier. The glycerol, released from triacyglycerol breakdown, is transported to liver, phosphorylated to glycerol 3-phosphate and converted to dihydroxyacetone phosphate (DHAP). DHAP can be used in glycolysis or more likely converted to glucose via gluconeogenesis to provide glucose for glucose-dependent tissues.
Metabolism of fatty acids
Activation of fatty acids and transport into mitochondria
Long-chain (>12 C) fatty acids are activated in the cytosol by esterification to coenzyme A (CoA), an ATP-consuming process, to form acylCoA esters (Figure 11.2). Oxidation of fatty acids occurs in the mitochondria, but the inner membrane is impermeable to acylCoA. Consequently the acyl group is transferred to carnitine and the acylcarnitine is transferred to the matrix using a shuttle system. Once in the matrix the long-chain acyl group is transferred to CoA and the carnitine exported to the cytosol via the shuttle. Short (2–4 C) and medium-chain (6–10 C) fatty acids pass directly into the mitochondrial matrix and form acylCoA there.
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