A high-performance liquid chromatographic method for the enantiomeric analysis of the enzymatically synthesized coenzyme A ester of 2-tetradecylglycidic acid

Weaner, Larry E.; Hoerr, David C.

doi:10.1016/0003-2697(87)90053-4

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…Using liver microsomal preparations, it was determined that only one of the enantiomers, ( R )‐2‐bromopalmitate, was a substrate for ACS 30. This finding is consistent with previous reports of stereoselectivity of ACS for other molecules 33,34…”

Section: The 2‐bromopalmitate Tracer Methods For Assessing Tissue‐specsupporting

confidence: 94%

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Evaluation of Free Fatty Acid Metabolism in Vivo

Oakes

Furler

2002

Annals of the New York Academy of Sciences

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In order to enable detailed studies of free fatty acid (FFA) metabolism, we recently introduced a method for the evaluation of tissue‐specific FFA metabolism in vivo. The method is based on the simultaneous use of 14C‐palmitate (14C‐P) and the non‐β‐oxidizable FFA analogue, [9,10‐3H]‐(R)‐2‐bromopalmitate (3H‐R‐BrP). Indices of total FFA utilization and incorporation into storage products are obtained from tissue concentrations of 3H and 14C, respectively, following intravenous administration of 3H‐R‐BrP and 14C‐P and their disappearance from plasma into tissues. This review covers the basis for, and developments in, the methodology, as well as some of the applications to date. In the rat, the method has been used to characterize tissue‐specific alterations in FFA metabolism in various situations, including skeletal muscle contraction, fasting, hyperinsulinemia, and various pharmacological manipulations. The results of all these studies clearly demonstrate tissue‐level control of FFA utilization and metabolic fate, refuting the traditional view that FFA utilization is simply supply‐driven. Recent developments enable the simultaneous evaluation of both tissue‐specific FFA and glucose metabolism by integrating the use of 2‐deoxyglucose and stable isotope‐labeled glucose tracers. In conclusion, the 3H‐R‐BrP methodology, especially in combination with other tracers, represents a powerful tool for elucidation of tissue‐specific fatty acid metabolism in vivo.

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Section: The 2‐bromopalmitate Tracer Methods For Assessing Tissue‐specsupporting

confidence: 94%

“…30 This finding is consistent with previous reports of stereoselectivity of ACS for other molecules. 33,34…”

Section: Activation By the Fatty Acid Sequestering Enzyme Acsmentioning

confidence: 99%

Evaluation of Free Fatty Acid Metabolism in Vivo

Oakes

Furler

2002

Annals of the New York Academy of Sciences

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“…This followed because the ACS-mediated activation step is required for commitment of FFA to the major pathways of fatty acid metabolism. The present findings are consistent with previous reports of stereoselectivity of ACS for other compounds (32,33).…”

Section: Validity Of R* F As An Estimate Of Tissue-specific Plasma Ffa Utilization Ratesupporting

confidence: 94%

Development and initial evaluation of a novel method for assessing tissue-specific plasma free fatty acid utilization in vivo using (R)-2-bromopalmitate tracer

Oakes

Kjellstedt

Forsberg

et al. 1999

Journal of Lipid Research

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We describe a method for assessing tissue-specific plasma free fatty acid (FFA) utilization in vivo using a non-␤ -oxidizable FFA analog, [9,10-3 H]-(R)-2-bromopalmitate ( 3 H-R-BrP). Ideally 3 H-R-BrP would be transported in plasma, taken up by tissues and activated by the enzyme acyl-CoA synthetase (ACS) like native FFA, but then 3 Hlabeled metabolites would be trapped. In vitro we found that 2-bromopalmitate and palmitate compete equivalently for the same ligand binding sites on albumin and intestinal fatty acid binding protein, and activation by ACS was stereoselective for the R-isomer. In vivo, oxidative and non-oxidative FFA metabolism was assessed in anesthetized Wistar rats by infusing, over 4 min, a mixture of 3 H-R-BrP and [U-14 C] palmitate ( 14 C-palmitate). Indices of total FFA utilization ( R * f ) and incorporation into storage products ( R fs ) were defined, based on tissue concentrations of 3 H and 14 C, respectively, 16 min after the start of tracer infusion. R * f , but not R fs , was substantially increased in contracting (sciatic nerve stimulated) hindlimb muscles compared with contralateral non-contracting muscles. The contraction-induced increases in R * f were completely prevented by blockade of ␤ -oxidation with etomoxir. These results verify that 3 H-R-BrP traces local total FFA utilization, including oxidative and non-oxidative metabolism. Separate estimates of the rates of loss of 3 H activity indicated effective 3 H metabolite retention in most tissues over a 16-min period, but appeared less effective in liver and heart. In conclusion, simultaneous use of 3 H-R-BrP and [ 14 C]palmitate tracers provides a new useful tool for in vivo studies of tissue-specific FFA transport, utilization and metabolic fate, especially in skeletal muscle and adipose tissue. -Oakes, N.

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“…However, to our knowledge, only two enzymatic approaches to the synthesis of ( R )- 1 and the parent TDGA have been found in the literature, i.e. by enantiotopic differentiation of prochiral 2-substituted glycerols with porcine pancreatic lipase (PPL) and by resolution of racemic TDGA through a rat liver microsomal enzyme preparation . Continuing our efforts directed to the enzyme-mediated chiral resolution of secondary alcohols, we present herein a new, short, and straightforward enantioselective synthesis of both enantiomers of 1 through enzymatic sequential kinetic resolution of racemic diol 3 followed by cyclization.…”

Section: Introductionmentioning

confidence: 99%

Lipase-Catalyzed Enantioselective Synthesis of Methyl (R)- and (S)-2-Tetradecyloxiranecarboxylate through Sequential Kinetic Resolution

1997

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Among a variety of lipases tested, Pseudomonas fluorescens lipase has been found to induce enantioselective acylation of methyl (R,S)-2-hydroxy-2-(hydroxymethyl)hexadecanoate (3), affording, through sequential kinetic resolution, both enantiomers in good optical yields. Efficiency of the process has been compared to the Sharpless asymmetric dihydroxylation of alkene 2 using (DHQD) 2 PHAL and (DHQ) 2 PHAL as chiral ligands. The (R)-and (S)-3 enantiomers have been cyclized to afford both enantiomers of methyl 2-tetradecyloxiranecarboxylate (1), a potent hypoglycemic agent and inhibitor of long-chain fatty acid oxidation.

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A high-performance liquid chromatographic method for the enantiomeric analysis of the enzymatically synthesized coenzyme A ester of 2-tetradecylglycidic acid

Cited by 7 publications

References 18 publications

Evaluation of Free Fatty Acid Metabolism in Vivo

Evaluation of Free Fatty Acid Metabolism in Vivo

Development and initial evaluation of a novel method for assessing tissue-specific plasma free fatty acid utilization in vivo using (R)-2-bromopalmitate tracer

Lipase-Catalyzed Enantioselective Synthesis of Methyl (R)- and (S)-2-Tetradecyloxiranecarboxylate through Sequential Kinetic Resolution

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