Synthesis and absolute configuration of the isomers of homoiscitric acid (1-hydroxy-1,2,4-butanetricarboxylic acid) and the stereochemistry of lysine biosynthesis

Chilina, Karen; Thomas, Ursula; Tucci, Anthony F.; McMichael, Kirk D.; Stevens, Calvin L.

doi:10.1021/bi00835a023

Cited by 15 publications

(5 citation statements)

References 21 publications

(24 reference statements)

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“…1 H NMR (CDCl 3 ): δ 2.02 (1H, m, H-4), 2.19 (1H, m, H′-4), 2.47 (2H, m, H-5), 3.01 (1H, dq, H-3), 3.35 (1H, d, J 1fOH ) 6.86 Hz, OH), 3.69, 3.71, 3.81 (3H each, s, methyl ester groups), 4.31 (1H, q, J 2f3 ) 3.43, J 2fOH ) 6.86 Hz, H-2). The (-)threo-isohomocitrate sample gave the same specific rotation as previously reported (15).…”

Section: Methodssupporting

confidence: 83%

α-Keto Acid Chain Elongation Reactions Involved in the Biosynthesis of Coenzyme B (7-Mercaptoheptanoyl Threonine Phosphate) in Methanogenic Archaea

Howell

Harich

et al. 1998

Biochemistry

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The biochemistry of the 13 steps involved in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to the coenzymes coenzyme B (7-mercapto heptanoylthreonine phosphate) and biotin, has been established in Methanosarcina thermophila. These series of reactions begin with the condensation of alpha-ketoglutarate and acetylCoA to form trans-homoaconitate. The trans-homoaconitate is then hydrated and dehydrated to cis-homoaconitate with (S)-homocitrate serving as an intermediate. Rehydration of the cis-homoaconitate produces (-)-threo-isohomocitrate [(2R,3S)-1-hydroxy-1,2, 4-butanetricarboxylic acid], which undergoes a NADP+-dependent oxidative decarboxylation to produce alpha-ketoadipate. The resulting alpha-ketoadipate then undergoes two consecutive sets of alpha-ketoacid chain elongation reactions to produce alpha-ketosuberate. In each of these sets of reactions, it has been shown that the homologues of cis-homoaconitate, homocitrate, and (-)-threo-isohomocitrate serve as intermediates. The protein product of the Methanococcus jannaschii MJ0503 gene aksA (AksA) was found to catalyze the condensation of alpha-ketoglutarate and acetylCoA to form trans-homoaconitate. This gene product also catalyzed the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologues of (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2, 6-hexanetricarboxylic acid. The alpha-ketosuberate resulting from this series of reactions then undergoes a nonoxidative decarboxylation to form 7-oxoheptanoic acid, a precursor to coenzyme B, and an oxidative decarboxylation to form pimelate, the precursor to biotin. Of the 13 intermediates in this pathway, eight have not previously been reported as occurring in biological systems.

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Section: Methodssupporting

confidence: 83%

α-Keto Acid Chain Elongation Reactions Involved in the Biosynthesis of Coenzyme B (7-Mercaptoheptanoyl Threonine Phosphate) in Methanogenic Archaea

Howell

Harich

et al. 1998

Biochemistry

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“…threo-( f )-Homoisocitrate was synthesized by Dr J. P. Fleury or by Dr P. Maldonado (Elf-Erap, F-69 Solaize) O r y n w . Homoisocitric dehydrogenase (EC 1.1.1.155) according to [9]. 2-Oxoadipic acid was from Sigma (St Louis, MO).…”

Section: Chemicalsmentioning

confidence: 99%

“…Standard conditions were: 1.5 mM potassium threo-( f)-homoisocitrate; 4.5 mM MgC12; 6 mM NAD in 0.1 M potassium phosphate buffer pH 8.5. No correction was made to account for the threo-(-) isomer being the actual substrate [3,9].…”

Section: Enrynatic Assaysmentioning

confidence: 99%

Wild‐Type and Mutant Forms of Homoisocitric Dehydrogenase in the Yeast Saccharomycopsis lipolytica

Gaillardin¹,

Ribet²,

Heslot³

1982

European Journal of Biochemistry

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Homoisocitric dehydrogenase (EC 1 .I .1 .I 55) has been purified 525-fold from the yeast Succharomycopsis lipoljtica with a yield of 25 ", . The preparation was judged to be homogeneous by electrophoresis under denaturing and non-denaturing conditions and by isoelectric focusing; it consisted of a single protein with molecular weight of 48000. In the presence of homoisocitric acid, a higher molecular weight was observed, suggesting a dimeric structure for the native enzyme.Complementing mutants devoid of homoisocitric dehydrogenase activity mapped at two closely linked loci (/w9 and /w10). Lysl0 mutants displayed NAD-reducing activity, whereas lys9 mutants retained some carboxylating activity.Our results are best explained by the assumption that the active enzyme is a dimer of identical subunits involved in successive dehydrogenation and decarboxylation steps.

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“…Racemic homoisocitric acid has been synthesized by condensation of diethyl glutarate with diethyl oxalate to triethyl 2-oxaloglutarate, which was reduced to the corresponding hydroxy ester and saponified to the racemic free acid . The absolute configurations of the four isomers of homoisocitric acid have been established by synthesis from the corresponding 2-hydroxy-3-cyclohexenecarboxylic acids of known absolute configuration . The threo d isomer of homoisocitric acid is a substrate for homoisocitric acid dehydrogenase .…”

Section: Introductionmentioning

confidence: 99%

Syntheses of (−)-Isocitric Acid Lactone and (−)-Homoisocitric Acid. A New Method of Conversion of Alkynylsilanes into the Alkynyl Thioether and Corresponding Carboxylic Acids

et al. 1996

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A simple, stereoselective synthesis of natural isocitric and homoisocitric acids from a common alkynylsilane correlates the stereochemistry of these acids. Starting with dimethyl D-malate dianion, methyl 2-hydroxy-3-carbomethoxy-6-(trimethylsilyl)-5-hexynoate (6a) was prepared with a good stereoselectivity (threo/erythro 90/10). Oxidative cleavage of the triple bond provided isocitric acid lactone (8') in 15% overall yield starting from D-malic acid diester 1. The synthesis of homoisocitric acid relied on a new method of conversion of alkynylsilane to alkynyl thioether, which is converted to the carboxylic acid of the same chain length. Addition of benzenesulfenyl chloride to (trimethylsilyl)alkyne 6b and elimination of trimethylsilyl chloride gave the corresponding thioether 10, which by acid hydrolysis gave homoisocitric acid (11) in a 24% yield from D-malic acid ester. This novel method of conversion of alkynylsilane to the corresponding acid was illustrated with several other alkynyltrimethylsilanes.

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Synthesis and absolute configuration of the isomers of homoiscitric acid (1-hydroxy-1,2,4-butanetricarboxylic acid) and the stereochemistry of lysine biosynthesis

Cited by 15 publications

References 21 publications

α-Keto Acid Chain Elongation Reactions Involved in the Biosynthesis of Coenzyme B (7-Mercaptoheptanoyl Threonine Phosphate) in Methanogenic Archaea

α-Keto Acid Chain Elongation Reactions Involved in the Biosynthesis of Coenzyme B (7-Mercaptoheptanoyl Threonine Phosphate) in Methanogenic Archaea

Wild‐Type and Mutant Forms of Homoisocitric Dehydrogenase in the Yeast Saccharomycopsis lipolytica

Syntheses of (−)-Isocitric Acid Lactone and (−)-Homoisocitric Acid. A New Method of Conversion of Alkynylsilanes into the Alkynyl Thioether and Corresponding Carboxylic Acids

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