Co2

Capillary

Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols.

Intestinal mucosa

ApoC-II

Fatty acids enter cells.

Lipoprotein lipase

© Lipoprotein lipase, activated by apoC-II in the capillary, converts triacylglycerols to fatty acids and glycerol.

© Chylomicrons move through the lymphatic system and bloodstream to tissues.

Chylomicron

© Triacylglycerols are incorporated, with cholesterol and apolipoproteins, into chylomicrons.

FIGURE 17-1 Processing of dietary lipids in vertebrates. Digestion and absorption of dietary lipids occur in the small intestine, and the fatty acids released from triacylglycerols are packaged and delivered to muscle and adipose tissues. The eight steps are discussed in the text.

FIGURE 17-2 Molecular structure of a chylomicron. The surface is a layer of phospholipids, with head groups facing the aqueous phase. Triacylglycerols sequestered in the interior (yellow) make up more than 80% of the mass. Several apolipoproteins that protrude from the surface (B-48, C-III, C-II) act as signals in the uptake and metabolism of chylomicron contents. The diameter of chylomicrons ranges from about 100 to 500 nm.

Apolipoproteins

Apolipoproteins

Lipid Mobilization Hormone
cholesteryl esters

Hormones Trigger Mobilization of Stored Triacylglycerols

Neutral lipids are stored in adipocytes (and in steroid-synthesizing cells of the adrenal cortex, ovary, and testes) in the form of lipid droplets, with a core of sterol esters and triacylglycerols surrounded by a monolayer of phospholipids. The surface of these droplets is coated with perilipins, a family of proteins that restrict access to lipid droplets, preventing untimely lipid mobilization. When hormones signal the need for metabolic energy, triacylglycerols stored in adipose tissue are mobilized (brought out of storage) and transported to tissues (skeletal muscle, heart, and renal cortex) in which fatty

Hormone

Adenylyl cyclase

Adenylyl cyclase

Figure Lehninger Principles

b oxidation, citric acid cycle, respiratory chain

Triacyl-glycerol

Bloodstream

FIGURE 17-3 Mobilization of triacylglycerols stored in adipose tissue. When low levels of glucose in the blood trigger the release of glucagon, @ the hormone binds its receptor in the adipocyte membrane and thus @ stimulates adenylyl cyclase, via a G protein, to produce cAMP. This activates PKA, which phosphorylates @ the hormone-sensitive lipase and @ perilipin molecules on the surface of the lipid droplet. Phosphorylation of perilipin permits hormonesensitive lipase access to the surface of the lipid droplet, where @ it hydrolyzes triacylglycerols to free fatty acids. @ Fatty acids leave the adipocyte, bind serum albumin in the blood, and are carried in the blood; they are released from the albumin and @ enter a myocyte via a specific fatty acid transporter. @ In the myocyte, fatty acids are oxidized to CO2, and the energy of oxidation is conserved in ATP, which fuels muscle contraction and other energy requiring metabolism in the myocyte.

b oxidation, citric acid cycle, respiratory chain

Triacyl-glycerol

Bloodstream

FIGURE 17-3 Mobilization of triacylglycerols stored in adipose tissue. When low levels of glucose in the blood trigger the release of glucagon, @ the hormone binds its receptor in the adipocyte membrane and thus @ stimulates adenylyl cyclase, via a G protein, to produce cAMP. This activates PKA, which phosphorylates @ the hormone-sensitive lipase and @ perilipin molecules on the surface of the lipid droplet. Phosphorylation of perilipin permits hormonesensitive lipase access to the surface of the lipid droplet, where @ it hydrolyzes triacylglycerols to free fatty acids. @ Fatty acids leave the adipocyte, bind serum albumin in the blood, and are carried in the blood; they are released from the albumin and @ enter a myocyte via a specific fatty acid transporter. @ In the myocyte, fatty acids are oxidized to CO2, and the energy of oxidation is conserved in ATP, which fuels muscle contraction and other energy requiring metabolism in the myocyte.

acids can be oxidized for energy production. The hormones epinephrine and glucagon, secreted in response to low blood glucose levels, activate the enzyme adenylyl cyclase in the adipocyte plasma membrane (Fig. 17-3), which produces the intracellular second messenger cyclic AMP (cAMP; see Fig. 12-13). Cyclic AMP-dependent protein kinase (PKA) phosphorylates perilipin A, and the phosphorylated perilipin causes hormone-sensitive lipase in the cytosol to move to the lipid droplet surface, where it can begin hydrolyz-ing triacylglycerols to free fatty acids and glycerol. PKA also phosphorylates hormone-sensitive lipase, doubling or tripling its activity, but the more than 50-fold increase in fat mobilization triggered by epinephrine is due primarily to perilipin phosphorylation. Cells with defective perilipin genes have almost no response to increases in cAMP concentration; their hormone-sensitive lipase does not associate with lipid droplets.

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mr 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel.

About 95% of the biologically available energy of tri-acylglycerols resides in their three long-chain fatty acids; only 5% is contributed by the glycerol moiety. The glyc-erol released by lipase action is phosphorylated by glyc-erol kinase (Fig. 17-4), and the resulting glycerol 3-phosphate is oxidized to dihydroxyacetone phosphate. The glycolytic enzyme triose phosphate isomerase converts this compound to glyceraldehyde 3-phosphate, which is oxidized via glycolysis.

Fatty Acids Are Activated and Transported into Mitochondria

The enzymes of fatty acid oxidation in animal cells are located in the mitochondrial matrix, as demonstrated in 1948 by Eugene P. Kennedy and Albert Lehninger. The fatty acids with chain lengths of 12 or fewer carbons enter mitochondria without the help of membrane transporters. Those with 14 or more carbons, which constitute the majority of the FFA obtained in the diet or released from adipose tissue, cannot pass directly through the mitochondrial membranes—they must first undergo the three enzymatic reactions of the carnitine shuttle. The first reaction is catalyzed by a family of isozymes (different isozymes specific for fatty acids having short, intermediate, or long carbon chains) present

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