Harpers

LIPID TRANSPORT & STORAGE / 217+++OUTSIDENorepinephinecAMPHormonesensitivelipaseTriacylglycerolFFA+Acyl-CoAF 0F 1ATPsynthaseH +H + HeatF 0+H +–PurinenucleotidesINNERMITOCHONDRIALMEMBRANERespiratorychainThermogeninCarnitinetransporterH +INSIDEReducingequivalentsHeatFigure 25–9. Thermogenesis in brown adipose tissue.Activity of the respiratory chain produces heat inaddition to translocating protons (Chapter 12). Theseprotons dissipate more heat when returned to theinner mitochondrial compartment via thermogenin insteadof generating ATP when returning via the F 1 ATPsynthase. The passage of H + via thermogenin is inhibitedby purine nucleotides when brown adipose tissueis unstimulated. Under the influence of norepinephrine,the inhibition is removed by the production of freefatty acids (FFA) and acyl-CoA. Note the dual role ofacyl-CoA in both facilitating the action of thermogeninand supplying reducing equivalents for the respiratorychain. + and − signify positive or negative regulatoryeffects.β-Oxidationtion, it must be concluded that insulin plays a prominentrole in the regulation of adipose tissue metabolism.BROWN ADIPOSE TISSUEPROMOTES THERMOGENESISBrown adipose tissue is involved in metabolism particularlyat times when heat generation is necessary. Thus,the tissue is extremely active in some species in arousalfrom hibernation, in animals exposed to cold (nonshiveringthermogenesis), and in heat production in thenewborn animal. Though not a prominent tissue in humans,it is present in normal individuals, where it couldbe responsible for “diet-induced thermogenesis.” It isnoteworthy that brown adipose tissue is reduced or absentin obese persons. The tissue is characterized by awell-developed blood supply and a high content of mitochondriaand cytochromes but low activity of ATPsynthase. Metabolic emphasis is placed on oxidation ofboth glucose and fatty acids. Norepinephrine liberatedfrom sympathetic nerve endings is important in increasinglipolysis in the tissue and increasing synthesis oflipoprotein lipase to enhance utilization of triacylglycerol-richlipoproteins from the circulation. Oxidationand phosphorylation are not coupled in mitochondriaof this tissue, and the phosphorylation that does occuris at the substrate level, eg, at the succinate thiokinasestep and in glycolysis. Thus, oxidation produces muchheat, and little free energy is trapped in ATP. A thermogenicuncoupling protein, thermogenin, acts as aproton conductance pathway dissipating the electrochemicalpotential across the mitochondrial membrane(Figure 25–9).SUMMARY• Since nonpolar lipids are insoluble in water, fortransport between the tissues in the aqueous bloodplasma they are combined with amphipathic lipidsand proteins to make water-miscible lipoproteins.• Four major groups of lipoproteins are recognized:Chylomicrons transport lipids resulting from digestionand absorption. Very low density lipoproteins(VLDL) transport triacylglycerol from the liver. Lowdensitylipoproteins (LDL) deliver cholesterol to thetissues, and high-density lipoproteins (HDL) removecholesterol from the tissues in the process known asreverse cholesterol transport.• Chylomicrons and VLDL are metabolized by hydrolysisof their triacylglycerol, and lipoprotein remnantsare left in the circulation. These are taken up by liver,but some of the remnants (IDL) resulting fromVLDL form LDL which is taken up by the liver andother tissues via the LDL receptor.