Term
| FAs are ________ to ketoacids and/or CO2 and H2O |
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Definition
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Term
| purpose and location of fatty acid synthesis |
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Definition
| energy storage. also FAs are precursors for CE, prostaglandins and other lipids. location - cytoplasm (substrates derived from mitochondrial metabolism) of liver and lactating mammary glands (and to a lesser degree in adipocytes) |
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Term
| substrates, products, regulation of FA synthesis |
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Definition
| s - acetyl coa (derived from citrate), p - FAs, r - fatty acid synthase complex, ACETYL COA CARBOXYLASE |
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Term
| FA degradataion purpose and location |
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Definition
| provision of energy. mitochondria of most tissues and cell types. ketogenesis occurs in liver. |
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Term
| FA degradation substrates, products, regulation |
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Definition
| s - FAs, p - CO2, water, energy (when completely oxidized) or ketone bodies. r - carnitine shuttle |
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Term
| within ___, FA oxidation accounts for a major proportion of energy expenditure |
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Definition
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Term
| advantages of FA as long term energy storage (3) |
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Definition
| high energy content (9Cal/g), storage in specialized cells allowing for large stores, provide a depot of substrate for structural lipids and signaling compounds like prostaglandins |
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Term
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Definition
| 4.8. hydrocarbon chain w/ terminal carboxyl group. at physiologic pH its ionized = amphipathic chain |
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Term
| more than 90% of FAs in plasma are |
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Definition
| esterified - triglycerides, CE, phospholipids. associated with proteins in lipoproteins. |
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Term
| unesterified FAs circulate bound to |
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Definition
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Term
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Definition
| originally trans fats (hydrogenated), now saturated vegetable oil (soy, palm) and unsaturated oils |
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Term
| unsaturated fats are _____ at room temperature |
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Definition
| oils. many membrane lipids are unsaturated = FLUID mosaic model |
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Term
| palmitic, linoleic, arachidonic |
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Definition
| p - 16C, l - 18C w/ 2 double bonds; essential, a - 20C with 4 double bonds; used for prostaglandin synthesis |
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Term
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Definition
| a - carboxyl group attached, o - terminal methyl carbon |
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Term
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Definition
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Term
| first step of FA synthesis |
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Definition
| shuttling acetyl coa in the form of citrate from the mitochondria to the cytosol |
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Term
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Definition
| citrate>acetylcoa(and OAA)>malonyl coa. 1. ATP-citrate lyase, 2. acetyl coa carboxylase |
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Term
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Definition
| prosthetic group for acetyl-coa carboxylase |
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Term
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Definition
| rate limiting enzyme for FA synthesis. uses biotin as a prosthetic group. activated by insulin and citrate, and inactivated by counter-regulatory hormones and palmatoyl coa. |
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Term
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Definition
| product of FA synthesis. precursor for triglycerides. |
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Term
| FA synthesis catalyzed by? reaction? |
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Definition
| malonyl coa + acetyl coa = palmitate. reduction reaction. catalyzed by fatty acid synthase complex. |
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Term
| main source of ______(energy product) from palmitate synthesis is __________ |
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Definition
| reduced NADP, the hexosemonophosphate pathway. however, NADPH is also derived from NADH. |
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Term
| acetylcoa+7malonyl-s-coa+14nadph+20H+ -> |
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Definition
| palmitate+7co2+8coaSH+14NADP++6water |
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Term
| fatty acid synthase complex |
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Definition
| cytosolic, ACP (acyl carrier protein) is essential, utilizes pantothenic acid. catalyzes palmitate synthesis. |
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Term
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Definition
| = pantothenic acid used by fatty acid synthase complex. = PA linked to serine by a phosphate group, and linked to an SH group at the other end. |
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Term
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Definition
| palmitic(16C)>palmitoleic. (desaturation) palmitic>steric(elongation)18C>oleic(elongation)18:1(9)>linoleic18:2>linolenic18:3>eicosatrienoic>arachidonic20:4>prostaglandins |
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Term
| elongation past C16 occurs in the |
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Definition
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Term
| production of very-long chain fatty acids occurs in the |
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Definition
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Term
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Definition
| occurs in the ER, catalyzed by mixed-function oxidases |
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Term
| why are linolenic, linoleic, eicosatrienoic essential? |
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Definition
| humans lack oxidases that can introduce double bonds past (less than) carbon 9 |
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Term
| triacylglycerol (triglyceride) synthesis occurs where (2), what for (2) |
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Definition
| liver and adipose tissue. for energy storage (adipose) and for exportation in the form of VLDL (liver) |
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Term
| fatty acids are _____ to glycerol through their _______ |
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Definition
| esterified, carboxyl groups |
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Term
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Definition
| fats whose carboxyl has been esterified, removing the negative charge at physiological pH. mono-, di-, and tri-acylglycerols. |
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Term
| FAs bound to glycerol in triglycerides: C1, C2, C3 |
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Definition
| C1 - usually saturated, c2 - usually unsaturated, c3 - either |
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Term
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Definition
| first step in FA oxidation. hydrolyzes triglycerides which releases FFAs from adipocytes |
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Term
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Definition
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Term
| triglycerides are converted to |
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Definition
| monoglycerides, then to FFA+glycerol (by hormone sensitive lipase) |
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Term
| glycerol metabolism accounts for __% of energy from triglycerides |
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Definition
| 5%. it is exported and taken up by liver where it enters the gluconeo/glycolysis pathway |
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Term
| HSL regulation (hormone sensitive lipase) |
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Definition
| activated by cAMP-dependent protein kinase, inactivated in reponse to dephosphorylation by insulin |
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Term
| FAs with chain length ____ require a system to transport them into the mitochondria. first step in transport system: ____ |
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Definition
| >12. acyl-coa synthesis by acyl-coa synthetase |
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Term
| 2nd step in transporting FAs to mitochondria for oxidation. take place where? |
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Definition
| CPTI, CPT II. CPTI: acyl-s-coa+carnitine>acyl-carnitine+coa-sh. CPTII: acyl-carnitine+coa-sh>acyl-s-coa+carnitine. take place at outer and inner mitochondrial membrane (IMM/OMM) |
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Term
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Definition
| requires 2ATP equivalents. RCOOH+ATP+COASH>RCO-S-COA+AMP+PPi |
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Term
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Definition
| carnitine palmitoyl transferase, also called CAT (acyl) |
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Term
| only oxidation of ____ fats is subject to regulation because ____ |
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Definition
| long-chain; because the carnitine shuttle is the main point of regulation in FA oxidation |
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Term
| carnitine comes from where |
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Definition
| meat in diet, synthesized in liver from lysine and methionine. stored mostly in skeletal muscle (>90%). |
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Term
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Definition
| primary: inability to synthesize or defective renal absorption, secondary: wasting of carnitine from disordered FA oxidation, CPTI deficiency: affects liver and causes hypoglycemia, CPTII deficiency: affects cardiac and skeletal muscle and causes muscle weakness in those areas |
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Term
| most energy derived from fat is a result of |
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Definition
| beta oxidation (>acetylcoa) |
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Term
| when does beta oxidation start? |
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Definition
| after hormone sensitive lipase and mitochondrial transport |
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Term
| 1st beta oxidation reaction, catalyzed by what |
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Definition
| fatty acyl-s-coa+ETF-FAD>enoyl-s-coa+ETF-FADH2, acyl-coa dehydrogenases (SACD,MACD,LACD,VLACD) |
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Term
| upon catalyzing the acyl-coa dehydrogenase reaction, _____ is reduced |
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Definition
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Term
| where does the energy from the FADH2 from beta oxidation go? |
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Definition
| to the mitochondrial respiratory chain -> net synthesis of 2ATP |
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Term
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Definition
| electron transferring flavoprotein |
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Term
| the 2nd part of beta oxidation = |
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Definition
| palmitate oxidation. enoyl-coa=palmitate? net reaction: palmitoyl-s-coa+7coa-sh+7fad+7nad+7water>8acetyl-s-coa+7fadh2+7nadh+7h |
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Term
| energy balance: palmitate oxidation |
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Definition
| 2atp/fadh+3atp/nadh=35atp. 8 acetyl coa = 96atp (TCA+oxidative phosphorylation). total = 131ATP/mole palmitoyl-coa |
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Term
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Definition
| produced in the liver since ATP can't be exported out. 2acetyl-s-coa+water>acetoacetate+2coa-sh |
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Term
| acetoacetate is further converted to |
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Definition
| beta hydroxybutyrate (catalyzed) and to trace amounts of acetone (not catalyzed) |
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Term
| acetone can be detected as |
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Definition
| a fruity odor to the breath |
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Term
| T/F - ketone body formation is irreversible |
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Definition
| false. the opposite reaction occurs "in the periphery". = ketone body metabolism. yields NADH. |
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Term
| ketogenesis can be thought of as a _________ pathway |
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Definition
| overflow. in the fasted state, OAA that's usually in TCA goes to gluconeogenesis, so acetyl coa can't go to TCA and therefore goes to ketone formation. |
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Term
| hepatic ketogenesis is favored when _________ is low |
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Definition
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Term
| rate limiting enzyme in acetoacetate formation |
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Definition
| HMG-CoA synthase, present in highest levels in the liver. |
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Term
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Definition
| liver, because HMG-CoA synthase is present there most often |
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Term
| ______ prefers ketones and ________ switches over during a fast |
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Definition
| myocardium, brain and muscle cells |
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Term
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Definition
| lack of insulin > lipolysis > ketogenesis |
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Term
| alternative oxidation of FAs (2) |
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Definition
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Term
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Definition
| metabolizes fats that beta can't. located in peroxisomes. produces alpha hydroxy FAs. is substrate driven. defective in Refsum's disease = alpha-hydroxylase deficiency. |
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Term
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Definition
| extra-mitochondrial / microsomal location, produces dicarboxylic FAs. substrate-driven regulation. upregulated if beta oxidation is defective. |
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Term
| regulation of FA metabolism is primarily... |
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Definition
| at CPT I, outer MM. inhibited by malonyl-coa, which means that acetyl-coa carboxylase is therefore the primary regulatory point. |
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Term
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Definition
| 1. activates acetyl-coa carboxylase=promotes FA synthesis, 2. inhibits oxidation at mitochondrial transport step by increasing malonyl-coa, which inhibits CPT-I (technically same mechanism at point #1), 3. promotes FA synthesis by increasing content of ATP-citrate lyase and FA synthase, 4. increases production of OAA from pyruvate, providing substrate for FA synthesis and inhibiting ketogenesis. (+ glucose>pyruvate, citrate>acetyl-coa, acetyl-coa>malonyl-coa, malonyl-coa>FA. - fatty acyl-coa>fatty acyl-carnitine) (memorize diagram) |
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Term
| disorders of FA oxidation |
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Definition
| manifest during periods of catabolism since beta oxidation is activated during fasting. most common = MCAD deficiency, causes SIDS, is screened for in newborns. dehydrogenase defect results in build-up of dicarboxylic FAs from omega oxidation (since they are chain length specific). ETF deficiency = impairment of all dehydrogenases = glutaric academia type II. |
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Term
| MCAD deficiency presents how / treatment |
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Definition
| low sugar, but unexpectedly, no ketonuria. blood tests show 8 9 and 10 C acid buildups. t - avoid fasts, deliver IV carb and carnitine during periods of stress |
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Term
| why does MCAD deficiency present in infancy? |
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Definition
| medium-chain fats are most present in human milk |
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Term
| precursor for triglycerides |
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Definition
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