Human Metabolism. Keith N. Frayn

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but in most cells there are multiple, small lipid droplets.

Figure shows the parallel between soap manufacture, called saponification, and fat mobilisation. In saponification, an alkali, usually NaOH, is used to hydrolyse a source of triacylglycerol, either animal fat or a vegetable oil. The resultant sodium salts of fatty acids, together with glycerol, constitute soap. The hydrolysis of triacylglycerol stored in adipocytes is similar, but brought about by enzymes, and releases non-esterified fatty acids that may be used as a fuel in other tissues. However, in metabolism, unlike in soap manufacture, the process is reversible: fatty acids can also be re-esterified with glycerol to make new triacylglycerols. This is the basis of the pathway by which triacylglycerol is laid down in adipocytes.

      1.3.3.2 Fat deposition and mobilisation

      Most dietary fat is in the form of triacylglycerol (Table 4.1). Within the small intestine, dietary triacylglycerol molecules are hydrolysed by intestinal lipases and the products are absorbed into the cells lining the intestines (mucosal or epithelial cells, collectively known as enterocytes). The products of lipolysis are recombined with the enterocytes to form new triacylglycerol. These triacylglycerols, composed of dietary fat, are liberated into the circulation as lipoprotein particles: in fact, the largest and most fat-enriched of the lipoprotein particles, known as chylomicrons (more detail in Chapters 4 and 10). At target tissues, the triacylglycerol in the lipoprotein particles is hydrolysed by a lipase bound to the endothelial cells lining the capillaries, known as lipoprotein lipase. The resulting fatty acids are taken up by cells, and have two potential fates: (i) re-esterification with glycerol 3-phosphate to make new triacylglycerol (and other lipids) – the pathway of fat deposition; or (ii) oxidation. The former is the major route by which dietary fat is laid down for storage in adipose tissue (Figure 1.17; Section 5.2.2.1).

      1.3.3.3 Fatty acid oxidation

      Following uptake into cells, fatty acids are rapidly ‘activated’ by esterification to CoA, forming fatty acyl-CoA; this esterification (known as thio- esterification because of the –SH thio group of the CoA molecule) also removes the amphipathic, detergent-like character of the fatty acid, making it less toxic in the membrane-rich cytosol. This reaction requires ATP and releases inorganic pyrophosphate, PPi. PPi is rapidly broken down to Pi, meaning that this step is essentially irreversible. It therefore achieves the same end as glucose phosphorylation to glucose 6-phosphate on entering a cell: it both traps the fatty acid within the cell, and creates a concentration gradient to draw more fatty acids into the cell. The enzymes concerned are known as acyl-CoA synthases (ACSs): again there is a family of these, suited for fatty acids of different carbon chain lengths. The action of the ACSs may be intimately linked to the process of fatty acid transport into the cell, discussed further in Chapter 2.

      The fatty acyl moiety may then undergo β-oxidation to yield acetyl-CoA (together with NADH and FADH2) for further oxidation and ATP formation (Figure 1.16 and Box 1.7). This process occurs in mitochondria (hence cells lacking this organelle, such as

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