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Introduction

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High-Yield Terms

  • Adipose tissue triglyceride lipase (ATGL): primary rate-limiting enzyme involved in adipose tissue triglyceride metabolism

  • Hormone-sensitive lipase (HSL): an adipose tissue–specific hydrolase responsible for the release of fatty acids from stored triglycerides. Its activity is regulated by hormone-mediated phosphorylation

  • α-oxidation: peroxisomal oxidation pathway responsible for the oxidation of the methyl-substituted fatty acid, phytanic acid present at high concentration in the tissues of ruminants

  • β-oxidation: major pathway for oxidation of fatty acids in both the mitochondria and the peroxisomes; peroxisomal β-oxidation is also important for metabolism of dicarboxylic acids generated via the ω-oxidation pathway

  • ω-oxidation: a minor, but clinically significant, pathway for fatty oxidation initiated by microsomal ω-hydroxylation reactions, also involves the oxidation of dicarboxylic acids generated

  • Ketone body: any of the compounds, β-hydroxybutyrate, acetoacetate, and acetone, generated during hepatic ketogenesis from the substrate, acetyl-CoA

  • Diabetic ketoacidosis (DKA): a condition of increased plasma ketone body concentration caused by excess adipose tissue fatty acid release and hepatic fatty acid oxidation resulting from unregulated glucagon release

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High-Yield Concept

Following absorption of the products of lipid digestion, the resynthesis of TGs, cholesterol esters, and phospholipids occurs. These lipid entities are then solubilized in lipoprotein complexes called chylomicrons. Chylomicrons from the intestine are then released into the blood via the lymph system for delivery to the various tissues for storage or production of energy through oxidation.

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Dietary Origins of Lipids

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The predominant form of dietary lipid in the human diet is triglyceride (TG or TAG). Gastrointestinal lipid digestion and absorption is discussed in Chapter 43. Briefly, the digestion of dietary triglyceride begins in the stomach with the action of gastric lipase and continues in the duodenum via the concerted actions of gastric lipase and pancreatic lipase. Digestion of dietary phospholipids takes place in the duodenum as well via the action of pancreatic phospholipase A2 (PLA2), yielding free fatty acids and lysophospholipids. Digestion of dietary cholesterol esters results via the action of carboxyl ester lipase (CEL). Intestinal absorption of diacyl- and monoacylglycerides, lysophospholipids, free fatty acids, and cholesterol occurs at the interface between the brush border membranes of intestinal enterocytes and the lipid micelles and involves both passive diffusion and transport protein–mediated uptake mechanisms.

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Discussion of the various lipoproteins present in human circulation can be found in Chapter 28. As chylomicrons circulate in the vasculature, fatty acids are removed from the TG fraction through the action of endothelial cell–associated lipoprotein lipase (LPL). The free fatty acids are then absorbed by the cells and the glycerol is returned via the blood to the liver where it is utilized as a carbon skeleton for glucose synthesis via gluconeogenesis (Chapter 13).

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High-Yield Concept

An additional lipase, lysosomal acid lipase (LAL), plays an important role in the intracellular degradation of cholesterol esters and TGs taken into cells via endocytosis and transferred to the lysosomes. The importance of LAL ...

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