Chapter 31: Synthesis of Fatty Acids, Triacylglycerols, and the Major Membrane Lipids

Fatty acid synthesis originates from acetyl-CoA derived from glucose metabolism, which is transported from mitochondria as citrate and sequentially processed by acetyl-CoA carboxylase to form malonyl-CoA, then by fatty acid synthase to generate the sixteen-carbon saturated fatty acid palmitate. Further enzymatic modifications through elongation and desaturation reactions expand the diversity of fatty acids available for cellular functions. Essential fatty acids, including linoleic and alpha-linolenic acid obtained through diet, serve as precursors for the synthesis of arachidonic acid, a critical substrate for eicosanoid production. Eicosanoids encompass prostaglandins, thromboxanes, and leukotrienes, which exert powerful regulatory effects on inflammatory responses, vascular function, hemostasis, and smooth muscle physiology through cyclooxygenase and lipoxygenase pathways. The therapeutic mechanisms of aspirin and nonsteroidal anti-inflammatory drugs operate through cyclooxygenase inhibition, while selective cyclooxygenase-2 inhibitors present distinct advantages and liabilities in clinical practice. Triacylglycerol synthesis proceeds through the glycerol 3-phosphate pathway and culminates in packaging within very-low-density lipoproteins for transport to peripheral tissues, where lipoprotein lipase releases fatty acids for energy utilization or storage. Adipose tissue functions not merely as an inert lipid depot but as an active endocrine organ secreting hormones such as leptin and adiponectin that regulate energy expenditure, appetite signaling, and insulin sensitivity. Membrane lipid synthesis involves the formation of glycerophospholipids and sphingolipids, molecules fundamental to cellular membrane architecture, pulmonary surfactant function, and myelin insulation. Pathological states including hyperlipidemia, metabolic syndrome, obesity, atherosclerosis, and neonatal respiratory distress syndrome are analyzed through the lens of dysregulated lipid metabolism, with therapeutic interventions including statins, nicotinic acid, and corticosteroids presented as pharmacological approaches to restore metabolic balance.