Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Lipid Transport and Storage
Metabolic Transformations in Adipose Tissue and Fat Mobilization — Metabolic Pathways (Fig. 26.8)

Triacylglycerols stored in adipose tissue undergo continuous lipolysis (Hydrolysis) and re-Esterification (Fig. 26.8). These transformations are not simply the forward and reverse reactions of a single pathway; rather, they proceed via distinct routes involving different reactants and Enzymes. Many metabolic, hormonal, and nutritional factors that regulate adipose tissue METABOLISM exert their effects on either esterification or lipolysis. The net outcome of these two processes determines the size of the free fatty acid pool within adipose tissue, which in turn serves as the source of plasma free Fatty acids and dictates their circulating levels. Because metabolism in other Tissues—most notably The Liver and Muscles—relies heavily on plasma free fatty acid levels, the factors acting within adipose tissue to regulate the release of free fatty acids exert far-reaching systemic effects well beyond this tissue.

Esterification and Lipolysis

Triacylglycerols are synthesized in adipose tissue from acetyl-CoA and glycerol-3-phosphate via the pathway shown in Fig. 25.1. Due to the very low activity of glycerol kinase in adipose tissue, glycerol is virtually excluded from direct participation in esterification. Instead, the glycerol-3-phosphate required for triacylglycerol synthesis is generated from glucose taken up from the Blood.

Triacylglycerols are hydrolyzed by hormone-sensitive lipase to yield free fatty acids and glycerol. This enzyme is distinct from lipoprotein lipase, which catalyzes the hydrolysis of lipoprotein triacylglycerols prior to their uptake by extrahepatic tissues (see p. 262). Because adipose tissue lacks The ability to utilize glycerol, it diffuses into the Blood Plasma and is transported to tissues such as the liver or Kidneys, where further metabolism occurs thanks to an active glycerol kinase. The free fatty acids generated during lipolysis are converted into acyl-CoA within adipose tissue by acyl-CoA synthetase and subsequently re-esterified with glycerol-3-phosphate to form triacylglycerols. Thus, adipose tissue maintains a continuous cycle comprising both lipolysis and esterification. However, when The rate of lipolysis exceeds that of esterification, free fatty acids accumulate in the tissue and diffuse into the plasma, where they bind to serum albumin, thereby elevating plasma free fatty acid levels. These plasma free fatty acids serve as a major energy source for numerous tissues.

Glucose Metabolism

When glucose uptake by adipose tissue increases, the efflux of free fatty acids decreases, whereas glycerol output continues unabated. This indicates that glucose action does not suppress the rate of lipolysis. Instead, it is believed that glucose provides the necessary glycerol-3-phosphate, which is subsequently esterified with fatty acid-CoA derivatives.

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Fig. 26.8. Metabolic Pathways in adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, Glucagon, epinephrine, norepinephrine, and vasopressin, and is inhibited by Insulin, prostaglandin E₁, and nicotinic acid. Details regarding The formation of glycerol-3-phosphate from glycolytic intermediates are provided in Fig. 25.1. PPP — Pentose Phosphate Pathway; TG — triacylglycerol; FFA — free fatty acids; VLDL — very-low-density Lipoproteins.

Adipose tissue utilizes several pathways for glucose metabolism, including oxidation to CO₂ via The Citric Acid Cycle, oxidation through The pentose phosphate pathway, conversion into long-chain fatty acids, and incorporation into acylglycerols (in the form of glycerol-3-phosphate). When glucose is abundantly available in adipose tissue, the majority is oxidized to CO₂ or converted into fatty acids. Conversely, when glucose availability drops, most of it is channeled into the synthesis of glycerol-3-phosphate and subsequent acylglycerols, thereby minimizing the net release of free fatty acids.

Uptake of Free Fatty Acids

Adipose tissue contains at least two distinct pools of free fatty acids. The free fatty acid pool (Fig. 26.8, Pool 1) generated via triacylglycerol hydrolysis is identical to the pool that undergoes re-esterification, and fatty acids from this pool are also released into the plasma. In contrast, fatty acids taken up from the extracellular environment following the action of lipoprotein lipase on chylomicron and VLDL triacylglycerols constitute a separate pool (Pool 2); radiolabeled fatty acids from Pool 2 can enter Pool 1 only after being incorporated into triacylglycerols.