Lippincott's Biochemistry Chapter 16 - Fatty Acid, Triacylglycerol, and Ketone Body Metabolism PDF

Fatty Acid, Triacylglycerol, and Ketone Body Metabolism I. OVERVIEW Fatty acids exist free in the body (that is, they are nonesterified) and as fatty acyl esters in more complex molecules such as triacylglycer- ols {TAG). Low levels of free fatty acids (FFA) occur in all tissues, but substantial a...

Fatty Acid, Triacylglycerol, and Ketone Body Metabolism I. OVERVIEW Fatty acids exist free in the body (that is, they are nonesterified) and as fatty acyl esters in more complex molecules such as triacylglycer- ols {TAG). Low levels of free fatty acids (FFA) occur in all tissues, but substantial amounts can sometimes be found in the plasma, particular1y during fasting. Plasma FFA (transported on serum albumin) are in route from their point of origin (TAG of adipose tissue or circulating lipopro- teins) to their site of consumption (most tissues). FFA can be oxidized by many tissues, particularly liver and muscle, to provide energy and, in the liver, to provide the substrate for ketone body synthesis. Fatty acids are also structural components of membrane lipids, such as phospholip- ids and glycolipids (see p. 201 ). Fatty acids attached to certain proteins enhance the ability of those proteins to associate with membranes (see p. 206). Fatty acids are also precursors of the hormone-like prostaglan- dins (seep. 213). Esterified fatty acids, in the form of TAG stored in white adipose tissue (WAT}, serve as the major energy reserve of the body. Alterations in fatty acid metabolism are associated with obesity and dia- betes. Figure 16.1 illustrates the metabolic pathways of fatty acid synthe- sis and degradation and their relationship to carbohydrate metabolism. II. FATIY ACID STRUCTURE Figure 16.1 Triacylglycerol synthesis and A fatty acid consists of a t"rjdrophobic hydrocarbon chain with a terminal degradation. CoA = coenzyme A. carboxyl group that has a pKa (seep. 6) of-4.8 (Fig. 16.2). At physiologic pH, the terminal carboxyl group (-COOH) ionizes, becoming-COO-. [Note: When the pH is above the pK, the deprotonated form predominates (see p. 7).] This anionic group has an affinity for water, gMng the fatty acid its amphipathic nature (having both a hydrophilic and a hydrophobic region). However, for long-chain-length fatty acids (LCFA), the hydrophobic por- tion is predominant. These molecules are highly water insoluble and must be transported in the circulation in association with protein. More than Figure 16.2 90% of the fatty acids found in plasma are in the form of fatty acid Structure of a fatty acid. esters (primarily TAG, cholesteryl esters, and phospholipicls) contained in 181 182 16. Fatty Acid, Triacylglycerol, and Ketone Body Metabolism circulating lipoprotein particles (seep. 227). FFA are transported in the cir- no culation in association with albumin, the most abundant protein in serum. w 'c -o- A. Fatty acid saturation Fatty acid chains may contain no double bonds (that is, be saturated) or contain one or more double bonds (that is, be mono- or polyunsatu- -+-Seturated ~ rated). In humans, the majority are sabJrated or monounsabJrated. When bond Unsaturated~ double bonds are present, they are nearty always in the cis rather than bond in the trans configuration. The introduction of a cis double bond causes {cla canftguratlan) the fatty acid to bend or kink at that position (Rg. 16.3). If the fatty acid has two or more double bonds, they are always spaced at three-car- bon intervals. [Note: In general, addition of double bonds decreases the melting temperature (Tm) of a fatty acid, whereas increasing the chain length increases the Tm. Because membrane lipids typically contain LCFA, the presence of double bonds in some fatty acids helps Figure 18.3 maintain the fluid nature of those lipids. Seep. 363 for a discussion of A saturated (A) and an unsaturated the dietary occul1'8nce of cis and trans unsaturated fatty acids.] (B} fatty acid. Orange denotes hydrophobic portions of the B. Fatty acid chain length and double bond positions molecules. [Note: Cis double bonds cause a fatty acid to kink.] The common names and structures of some fatty acids of physiologic importance are listed in Figure 16.4. In humans, fatty acids with an even number of carbon atoms (16, 18, or 20) predominate, with longer Fatly acids wtlh chain langlha of 4 to 10 carbana are found In fatty acids (>22 carbons) being found in the brain. The carbon atoms algnHlcant quanllllee In mllk. are numbered, beginning with the carbonyl carbon as carbon 1. The Stn.ictural lipids and b1acy1g1yeero1s number before the colon indicates the number of carbons in the chain, contain prtmarlly fatty acids of at and those after the colon indicate the numbers and positions (rela- leaet 1$ carbons. tive to the carboxyl end) of double bonds. For example, as denoted in Figure 16.4, arachidonic acid, 20:4{5,8,11,14), is 20 carbons long and has four double bonds (between carbons 5-6, 8-9, 11-12, and 14-15). [Note: Garbon 2, the carbon to which the carboxyl group is attached, is also called the a-carbon, carbon 3 is the ~carbon, and carbon 4 is 2:0 the y-carbon. The carbon of the terminal methyl group is called the Propionic acid 3:0 6)-CB.rbon regardless of the chain length.] The double bonds in a fatty Butyric acid 4:0 acid can also be referenced relative to the m(methyl) end of the chain. Arachidonic acid is referred to as an co-6 fatty acid because the ter- Capric acid minal double bond is six bonds from the ro end (Fig. 16.5A). [Note: Palmitic acid 16:0 The equivalent designation of n-6 may also be used (Fig. 16.58).] Palmitoleic acid 16:1(9) Another ro-6 fatty acid is the essential linoleic acid 18:2(9,12). In contrast, Stearic acid 18:0 a-linolenic acid, 18:3(9,12,15), is an essential ID-3 fatty acid. Oleicacid 18:1(9) Linoleic acid 18:2(9,12) C. Essentlal fatty acids a-Linolenic acid 18:3(9,12,15) Linoleic acid, the precursor of {i)-6 arachidonic acid that is the sub- Arachidonic acid 20:4(5, 8,11,14 strate for prostaglandin synthesis (see p. 213), and a-linolenic acid, Lignoceric acid 24:0 the precursor of ro-3 fatty acids that are important for growth and 24:1(15) development, are dietary essentials in humans because we lack the Neivonic acid enzymes needed to synthesize them. Plants provide us with these Precursor of prostaglandins essential fatty acids. [Note: Arachidonic acid becomes essential if lin- Essential fatty acids oleic acid is deficient in the diet. See p. 362 for a discussion of the nutritional significance of ro-3 and ro-6 fatty acids.] Flgure 16.4 Some fatty acids of physiologic Essential fatty acid deficiency (rare) can result in a dry, scaly importance. [Note: A fatty acid containing dermatitis as a result of an inability to synthesize molecules 2-4 carbons Is considered short; 6-12, medium; 14-20, long; and ~.very long.] 11 that provide the water barrier In skin (see p. 206). Ill. Fatty Acid De Novo Synthesis 183 Ill. FATTY ACID DE NOVO SYNTHESIS Carbohydrates and proteins obtained from the diet in excess of the body's needs for these nutrients can be converted to fatty acids. In aduHs, de novo fatty acid synthesis occurs primarily in the liver and lactating mammary glands and, to a lesser extent, in adipose tissue. This cyto- ~~ ~~ ~~ ' solic process is endergonic {see p. 70) and reductive. It incorporates car- HOOC{CHpjpC-CHf C= C-Qi.,z-&=.C-CHi-C; C bons from acetyl coenzyme A (CoA) into the growing fatty acid chain, using ATP and reduced nicotinamide adenine dinucleotide phosphate {NADPH). [Note: Dietary TAG also supply fatty acids. See p. 321 for a discussion of the metabolism of dietary nutrients in the well-fed state.] A. Cytosolic acetyl CoA production The first step in fatty acid synthesis is the transfer of acetate units from mitochondrial acetyl CoA to the cytosol. Mitochondrial acetyl CoA is produced by the oxidation of pyruvate (see p. 109) and by the catabo- lism of certain amino acids (seep. 266). However, the CoA portion of acetyl CoA cannot cross the inner mitochondrial membrane, and Flgure16.5 only the acetyl portion enters the cytosol. It does so as part of citrate Arachidonic acid, 20:4(5,8,11,14), produced by the condensation of acetyl CoA with oxaloacetate (OAA) illustrating the position of the double by citrate synthase (Fig. 16.6). [Note: The transport of citrate to the bonds. A. Arachidonic acid is an m-6 fatty acid because the first double cytosol occurs when the mitochondrial citrate concentration is high. bond from the (I) end is 6 carbons This is observed when isocitrate d8hydrogsnasa of the tricarboxylic from that end. B. It Is also referred acid (TCA) cycle is inhibited by the presence of large amounts of ATP, to as an n-6 fatty acid because the causing citrate and isocitrate to accumulate (see p. 112). Therefore, last double bond from the carboxyl cytosolic citrate may be viewed as a high-energy signal. Because a end is 14 carbons from that end: 20 - 14 =6 =n. Thus, the "oo" and "n" large amount of ATP is needed for fatty acid synthesis, the increase in designations are equivalent (see ). both ATP and citrate enhances this pathway.] In the cytosol, citrate is cleaved to OAA and acetyl CoA by ATP citrate lysse. MITOCHONDRIAL MATRIX Oxaloacetate~I CoA B. Acetyl CoA carbox:ylatlon to malonyl CoA The energy for the carbon-to-carbon condensations in fatty acid syn- Cl1nlls S)'nlhase~= thesis is supplied by 1he carboxylation and then decarboxylation of Cltnde acyl groups in the cytosol. The carboxylation of acetyl CoA 10 malonyl CoA is ca1alyzed by acety/ CoA carboxylase (ACC) {Fig. 16.7). ACC transfers carbon dioxide (C02} from bicarbonate ( HC09-) in an ATP-requiring reaction. The coenzyme is biotin {vitamin B;-}, which is covalently bound to a lysyl residue of the carbaxylase {see Fig. 28.16, p. 385). ACC carboxylates the bound biotin, which transfers the acti- vated carboxyl group to acetyl CoA. Citrate 1. Acetyl CoA carboxylaaa short-term regulatlon: This carboxyl- ation is both the rate-limiting and the regulated step in fatty acid synthesis (see Fig. 16.7). The inactive form of ACC is a protomer (complex of ;::2 polypeptides). The enzyme is allosterically activated CoAl Hz(>~ ATP clfl'8f8 ~ ATP ADP+P1 by citrate, which causes protomers to polymerize, and allosteri- cally inactivated by palmitoyl CoA (the end product of the path- Oxaloacetate Acetyl CoA way), which causes depolymerization. A second mechanism of CYTOSOL short-term regulation is by reversible phosphorylation. Ad8nosine monophosphate-a.ctivatsd protein kinase (AMPK) phosphorylates Flgure16.6 and inactivates ACC. AMPKitself is activated allosterically by AMP Production of cytosolic acelyl and covalently by phosphorylation via several kinases. At least ccenzyme A (CoA). [Note: Citrate one of these AMPK kinases is activated by cyclic AMP (cAMP)- is transported by the tricarboxylate transporter system.] ADP "'adenosine dspendent protein kinase A (PKA). Thus, in the presence of coun- = monophosphate; P1 inorganic terregulatory hormones, such as epinephrine and glucagon, ACC is phosphate. 184 16. Fatty Acid, Triacylglycerol, and Katona Body Metabolism phosphorylated and inactive (Fig. 16.8). In the presence of insulin, 0 0 0 ACC is dephosphorylated and active. [Note: This is analogous to 0 0 0 0 the regulation of glycogen synthase (seep. 131).] AMyl CoA ~ (Inactive protomenl) 2. Acetyl CoA carboxylase long-term regulation: Prolonged con- sumption of a diet containing excess calories (particularly high- ca.rbohydrate, low-fat diets) causes an increase in ACC synthesis, CHratB ~ 0 0 ~""" PalmltDyl CoA thereby increasing fatty acid synthesis. A low-calorie or a high-fat, low-carbohydrate diet has the opposite effect. [Note: ACC syn- thesis is upregulated by carbohydrate (specifically glucose) via 0000>0000000 the transcription factor carbohydrate response element-binding At»WfCoA~8N protein (ChREBP) and by insulin via the transcription factor ste- (acllve polymer) rol regulatory element-binding protein-1c {SREBP-1c). Fatty acid a o synthase (see C. below) is similarly regulated. The function and " -0 II CHa-c-s-I T T :c-cH2-c-s-CoA regulation of SREBP are described on p. 222.] Metformin, used Acetyl CoA 0 Malonyl CoA in the treatment of type 2 diabetes, lowers plasma TAG through activation of AMPK, resulting in inhibition of ACC activity (by phos- HCo.- phorylation) and inhibition of ACC and fatty acid synthase expres- sion (by decreasing SREBP-1c). Metformin lowers blood glucose ATP ADP+P1 by increasing AMPK-mediated glucose uptake by muscle. Figure 16.7 C. Eukaryotic fatty acid synthase Allosteric regulation of malonyt coenzyme A (CoA) synthesis by SC9tyl The remaining series of reactions of fatty acid synthesis in eukaryotes CoA caJtx»ty1ass. The carboxyl group is catalyzed by the multifunctional, homodimeric enzyme fatty acid contributed b'f bicarbonate ( HC03 - ) is shown in blue. Pi= inorganic phosphate; synthase (FA61. The process involves the addition of two carbons ADP= adenosine diphosphate. from malonyl CoA to the carboxyl end of a series of acyl acceptors. Each FAS monomer is a multicatalytic polypeptide with six different enzymic domains plus a 4'-phosphopantetheine-containing acyl car- rier protein (ACP} domain. 4'-Phosphopantetheine, a derivative of pantothenic acid (vitamin B5. see p. 385), carries acyl units on its terminal thiol (-SH) group and presents them to the catalytic domains of FAS during fatty acid synthesis. It also is a component of CoA. [Note: In prokaryotes, FAS is a multienzyme complex.] The reaction numbers in brackets below refer to Figure 16.9. An acetyl group is transferred from acetyl CoA to the -SH group of the ACP. Domain: Ma/onyVacetyl CoA-ACP transacylase. AM~prollllti Next, this two-carbon fragment is transferred to a temporary hold- ADP ldnaN (AMPK) ing site, the -SH group of a cysteine residue on the condensing 0 ATP enzyme domain (see [4) below). The now-vacant ACP accepts a three-carbon malonyl group from ~4ra malonyl CoA. Domain: MaJonyVacety/ CoA-ACP transacytass. The acetyl group on the cysteine residue condenses with the 01111 malonyl group on ACP as the C02 originally added by ACC is released. The result is a four-carbon unit attached to the ACP domain. The loss of free energy from the decarboxylation drives the reaction. Domain: 3-Kstoacyl-ACP synthase, also known as Figure 16.8 condensing enzyme. Covalent regulation of acety/ CoA cal'.boxyfas6 by AMPK, which itself Is regulated both covalently and The next three reactions convert the 3-ketoacyl group to the corr&- = allosterically. CoA coenzyme A; sponding saturated acyl group by a pair of NADPH-requiring reduc- ADP and AMP =adenosine di- and tions and a dehydration step. = monophosphates: P phosphate: P1 =inorganic phosphate. Ill. Fatty Acid De Novo Synthesis 185 Cystelne coo- added by acetyl residue CoA carboxytase 0II SH cH.-c- s- CoA Acetyt CoA A SH n SH ~s-c- CH1 ' FATTY ACID SYNTHASE [4) Acyl carrier protein domain with 4'-phosphopantethelne (ACP-SH) H~ SH SH 0ti s - c - CH;;CH-~ [d s-c SH OOH CH2' C-CH1 H NADp+ NADPll + ( "-..! o o ACP s -C-CHi!- C - CH1 NADPH + H+ ~carbon,......ratad fatty a~ACP (butyryl-ACP) SH 0It 0u S - C - CH2- C- CH2- C"2- CHa rc;fsH PALMITATE W sH Figure 16.9 Synlhesls of palmltate (16:0) by multtfunctlonal fatty acid synthase. [Note: Numbers In brackets correspond to bracketed numbers In lhe text. A second repetition of the steps Is Indicated by numbers wllh an asterisk (*). Carbons provided dlreclly by acelyl coenzyme A (CoA) are shown in red.) ACP = acyl carrier protein domain; CO:! = carbon dioxide; NADP(H} = nicotinamide adenine dinucleotide phosphate. 186 16. Fatty Acid, Triacylglycarol, and Katona Body Metabolism The keto group is reduced to an alcohol. Domain: 3-Ketoacyl- 0 II ACP reductase. c-o- 1 A molecule of water is removed, creating a1ransdouble bond between C"O I carbons 2 and 3 (the a- and 13-Carbons). Domain: 3-Hydroxyaefr- CH2 ACP dehydrat8.S8. o'cO- The double bond is reduced. Domain: Enoyl-ACP reductase. This sequence of steps results in the production of a four-carbon group (butyryl) whose three terminal carbons are fully saturated and which remains attached to the ACP domain. The steps are repeated (indicated by an asterisk), beginning with the transfer of the butyryl unit from the ACP to the cysteine residue [2*], the attachment of a malonyl group to 1he ACP [3j, and the condensation of the two groups liberating C02 [4j. The carbonyl group at the J3--carbon (carbon 3, the 0 third carbon from the sulfur) is then reduced cs ], dehydrated [6j, c-o- 1 and reduced [7"], generating hexanoyl-ACP. This cycle of reactions is H-C -OH I repeated five more times, each time incorporating a two-carbon unit CH2 (derived from malonyl CoA) into the growing fatty acid chain at the I dco- carboxyl end. When the fatty acid reaches a length of 16 carbons, the Ma1a1a synthetic process is terminated with palmitoyl-S-ACP. [Note: Shorter- length fatty acids are produced in the lactating mammary gland.] PaJmitoyJ thiossterase, the final catalytic activity of FAS, cleaves the thioester bond, releasing a fully saturated molecule of palmitate (16:0). [Note: All the carbons in palmitic acid have passed through malonyt CoA except the two donated by the original acetyl CoA (the first acyl NADPH acceptor), which are found at the methyl (m) end of the fatty acid. This +H+ underscores the rate-limiting nature of the ACC reaction.] 0 " c-o- 1 D. Reductant sources C =O The synthesis of one palmitate requires 14 NADPH, a reductant I CHa (reducing agent). The pentose phosphate pathway {see p. 145) is a Pynnnde major supplier of the NADPH. Two NADPH are produced for each Reductive Qnlh I of molecule of glucose &phosphate that enters 1his pathway. The cyto- ratty acids, st9rolde, sawolt solic conversion of malate to pyruvate, in which malate is oxidized and ( Cytochrome P4SO system decarboxylated by cytosolic malic enzyme (NADP"-dependent ma/ate dehydrogenase), also produces cytosolic NADPH {and C02}, as shown I Detoxification of rwtlve oxygen lntttmedlates in Figure 16.10. [Note: Malate can arise from the reduction of OAA by cytosolic NADH-dependent malate dehydrogensse (see Fig. 16.10). One source of the cytosolic NADH required for this reaction is gly- Figure 16.1 o colysis (seep. 101). OAA, in turn, can arise from citrate deavage by CytOSOlic conversion of oxaloacetate ATP citrate Jysse.] A summary of the interrelationship between glucose to pyruvate with the generation of metabolism and pa.Imitate synthesis is shown in Figure 16.11. nicotinamide adenine dinucleotide phosphate (NADPH}. [Note: The pentose phosphate pathway is also E. Further elongatlon a source of NADPH.] NAD(H) "" AHhough palmitate, a 16-carbon, fully saturated LCFA (16:0), is the nicotinamide adenine dinucleotide; 002 =carbon dioxide. primary end product of FAS activity, it can be further elongated by the addition of two-earbon units to the carboxylate end primarily in the smooth endoplasmic reticulum (SER). Elongation requires a system of separate enzymes rather than a multifunctional enzyme. Malonyl CoA is the two-carbon donor, and NADPH supplies the electrons. The brain has additional elongation capabilities, allowing it to produce the very-long-chain fatty acids ([VLCFAJ over 22 carbons) that are required for synthesis of brain lipids. Ill. Fatty Acid De Novo Synthesis 187 1be glycolyllc pathway producee n Mltochondrl11I oxaloacetate ft 0 pyn.ivate, wtllch I the primary tource of the mltochondrlal U (OAA} Is produced by PC, the flret etep In the gluconeogenlc A.celyl CoA le produced l:il by PDH In mHochondrla and condeneee wtth OAA acetyl CoA to be uaed for fatty pathway. to form citrate, the ftrat acid 8Jl"lhelllL It alao producee st:ep In the TCA cycle. cytoaollc NADH, a reductant. Pyruvate entens the mitochondria. NAOPH NADP+.Ac:etyl CoA CoA D Citrate lellvN the mitochondria and le cleaved In the cytosol to produce cytoeollc acetyl CoA. f t Cyloeollc NADH produced during ft The carbon& of cytosollc acetyl CoA a~ 1:1 glycolyals contrtbutDll to the raducdon 1:.1 used to eynthealm palmltate, with of NADP+ to NADPH needed far pelmltoyl NADPH u the ntductent for the pathway. Co.A ayntheals. Figure 16.11 = = Interrelationship between glucose metabolism and palmitate synthesis. CoA coenzyme A:, NAD(H} nicotinamide adenine = = nucleotide; NADP(H) nicotinamide adenine dinucteotide phosphate; ADP adenosine diphosphate; P; "" inorganic phosphate; COa =carbon dioxide; TCA =tricarboxylic aeid; PC= pyruvate catboxylase; PDH =pyrovat8 dehydrogensse. F. Chain desaturation Enzymes (fatty acyl CoA dssaturases) also present in 1he SER are responsible for desaturating LCFA (that is, adding cis double bonds). The desaturation reactions require oxygen (02), NADH, cytochrome bs, and its flavin adenine dinucleotide (FAD)-linked rsductaS8. The fatty acid and the NADH get oxidized as the Qi gets reduced to HiQ. The first double bond is typically inserted between carbons 9 and 1O, producing primarily oleic acid, 18:1(9), and small amounts of palmi- toleic acid, 16:1(9}. A variety of polyunsaturated fatty acids can be made through additional desaturation combined with elongation. 188 16. Fatty Acid, Triacylglycarol, and Katona Body Metabolism H~~H Humans have carbon 9, 6, 5, and 4 desaturasss but lack the ability to introduce double bonds from carbon 10 to the ro end I HO of the chain. This is the basis for the nutritional essentiality of Glycerol the polyunsaturated ~ linoleic acid and ro-3 linolenic acid. Glycerol component of trlacylglycerol G. Storage as trlacylglycerol components 0~c-o?~~o-cJJ Mono-, di-, and triacylglycerols consist of one, two, or three mole- I cules of fatty acid esterified to a molecule of glycerol. Fatty acids are 0 o,,1 esterified through their carboxyl groups, resulting in a loss of negative "C charge and formation of neutral fat. [Note: An acylglycerol that is solid at room temperature is called a fat. If liquid, it is an oil.] 1. Arrangement: The three fatty acids esterified to a glycerol mol- ecule to form a TAG are usually not of the same type. The fatty acid on carbon 1 is typically saturated, that on carbon 2 is typically unsaturated, and that on carbon 3 can be either. Recall that the presence of the unsaturated fatty acid(s) decrease(s) the Tm of the lipid. An example of a TAG molecule is shown in Figure 16.12. 2. Trlacylglycerol storage and function: Because TAG are only slightly soluble in water and cannot form stable micelles by them- selves, they coalesce within white adipocytes to form large oily droplets that are nearly anhydrous. These cytosolic lipid droplets Figure 16.12 are the major energy reserve of the body. [Note: TAG stored in A triacylglycerol with an unsaturated brown adipocytes serve as a source of heat through nonshivering fatty acid on carbon 2. Orange thermogenesis (seep. 79).] denotes the hydrophobic portions of the molecule. 3. Glycerol 3-phosphate synthesis: Glycerol 3-phosphate is the initial acceptor of fatty acids during TAG synthesis. There are two major pathways for its production (Fig. 16.13). [Note: A third pro- cess (glyceroneogenesis) is described on p.190.] In both liver (the primary site of TAG synthesis) and adipose tissue, glycerol 3-phos- phate can be produced from glucose, first using the reactions of the glycolytic pathway to produce dihydroxyacetone phosphate ([DHAP], seep. 101}. DHAP is reduced by glycerol 3-phosphate LIVER t Glucoee GLYCOLYlllS Glucoee ! GLYCOLYSIS Dlhydroxym:etane phoephllte NADH -i G/ycerol 3-phosphllte Dlhydroxyacetone phoephat8 NAl'J+ ~dehydro(/enlv18 NADH j GJyr;emi~ ADP AlP Glycerol )..phosphate (=\.) NAo+ ~d8/rydlOg8n8tlt G-rol Glyc:8ld kinase ··- Glycerol 3-phosphate Figure 16.13 Pathways for production of glycerol 3·phosphate in liver and adipose tissue. [Note: Glycerol 3·phosphate can also be = = generated by glyceroneogenesis.] NAD(H) nicotinamide adenine dinucleotide; ADP adenosine diphosphate. IV. Fat Mobilization and Fatty Acid Oxidation 189 dehydrogenass to glycerol 3-phosphate. A second pathway found