Identification and partial characterization of inositol; NAD<sup>+</sup> epimerase and inosose: NAD(P)H reductase from the fat body of the American cockroach, Periplaneta americana

Hipps, Paul P.; Sehgal, Raj K.; Holland, William H.; Sherman, William R.

doi:10.1021/bi00747a025

Cited by 45 publications

(23 citation statements)

References 19 publications

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“…Gas chromatography was carried out by the method of Hipps et al (17) except that the absorbent was 3% methyl polysiloxy gum on Gas-Chrom Q (Applied Science Labs, Inc., State College, Pa.). The helium flow rate was 48 ml/min.…”

Section: Methodsmentioning

confidence: 99%

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Molitoris¹,

Hruska

Fishman

et al. 1979

J. Clin. Invest.

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A B S T R A C T The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-3H] 1110 release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover.

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Section: Methodsmentioning

confidence: 99%

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Molitoris¹,

Hruska

Fishman

et al. 1979

J. Clin. Invest.

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“…Substrates (2KMI, 1KDCI, and 1-keto-L-chiro-inositol [1KLCI]) were supplied by Hokko Chemical Industry. The reaction mixture (100 l) in 40 mM potassium phosphate buffer (pH 7.5) was composed of 88 g of the purified His 6 tag fusion IolI enzyme, 1 mM MnSO 4 , and 178 mM substrate (2KMI, 1KDCI, and 1KLCI). The mixture was incubated at 36°C for 120 min, and the reaction was terminated by the addition of DuoliteC20 (H ϩ type) and incubation at 50°C at 10 min.…”

Section: Vol 72 2006 D-chiro-inositol Production By B Subtilis 1311mentioning

confidence: 99%

“…In plants and insects, DCI is formed by an oxidoreductive epimerization of the C 1 hydroxyl of MI (4). A rich source of DCI is pinitol, a 3-Omethyl ether of DCI obtained from pinewood and legumes.…”

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confidence: 99%

Genetic Modification of Bacillus subtilis for Production of d - chiro -Inositol, an Investigational Drug Candidate for Treatment of Type 2 Diabetes and Polycystic Ovary Syndrome

Yoshida

Yamaguchi

Morinaga

et al. 2006

Appl Environ Microbiol

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D-chiro-Inositol (DCI) is a drug candidate for the treatment of type 2 diabetes and polycystic ovary syndrome, since it improves the efficiency with which the body uses insulin and also promotes ovulation. Here, we report genetic modification of Bacillus subtilis for production of DCI from myo-inositol (MI). The B. subtilis iolABC-DEFGHIJ operon encodes enzymes for the multiple steps of the MI catabolic pathway. In the first and second steps, MI is converted to 2-keto-MI (2KMI) by IolG and then to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione by IolE. In this study, we identified iolI encoding inosose isomerase, which converts 2KMI to 1-keto-D-chiroinositol (1KDCI), and found that IolG reduces 1KDCI to DCI. Inactivation of iolE in a mutant constitutively expressing the iol operon blocked the MI catabolic pathway to accumulate 2KMI, which was converted to DCI via the activity of IolI and IolG. The mutant was able to convert at least 6% of input MI in the culture medium to DCI.

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“…The reasons for this difference can be several. One possibility is that chiro-[3H]inositol is synthesized from a nonradioactive precursor as well as from myo-[3H]inositol, or that chiro-[3H]inositol is synthesized from a myo-[3H]inositol pool with a lower specific radioac-free myo-inositol as occurs in plants and insects through the oxidoreductive epimerase action (17).…”

Section: Discussionmentioning

confidence: 99%

Insulin stimulates the biosynthesis of chiro-inositol-containing phospholipids in a rat fibroblast line expressing the human insulin receptor.

Pak

Paule²,

Bao³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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HIREc-B cells (rat fibroblasts expressing the human insulin receptor) were incubated with myo-[3H]inositol for 48 hr, and the biosynthesis of chiro-[3HJinositol was investigated in the absence and presence of insulin following a time course up to 60 min. After phase separation, treatment with insulin for 15 min caused a 2.2-fold increase in the specific radioactivity of chiro-[3Hlinositol-containing phospholipids in contrast to a 1. The combination of D-chiro-inositol and galactosamine was originally discovered as an unexpected species of rat liver inositol phosphoglycan insulin mediator (1). A second species of insulin mediator, first described by Saltiel and Cuatrecasas (2), contained myo-inositol and glucosamine, the usual inositol and hexosamine commonly present in the inositol phosphoglycans. The chiro-inositol-containing mediator has been shown to activate pyruvate dehydrogenase phosphatase and glycogen synthase phosphatase (3, 4). Glycogen synthase and pyruvate dehydrogenase are the ratelimiting enzymes which control nonoxidative and oxidative insulin-sensitive glucose metabolic pathways, respectively. These two phosphatases are activated by insulin and the two pathways are now recognized to be defective in postreceptor insulin resistance in primates with type II diabetes (5). A lack of chiro-inositol together with an excess of myo-inositol has been noted in type II diabetic urine and skeletal muscle (5), leading us to suggest that insulin resistance may result from a possible defect in synthesis or metabolism of chiro-inositol (6). EXPERIMENTAL PROCEDURES Materials. Phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were obtained from Avanti Polar Lipids. PI 4,5-bisphosphate (PIP2), PI 4-phosphate (PIP), and lyso-PI were from Sigma. Silica gel G plates for thin-layer chromatography (TLC) were from Merck. Analytical-grade anion-exchange (AG1-X8) and cation-exchange (AG5OW-X8) resins were from Bio-Rad. All other reagents and chemicals were purchased from Sigma at analyticalgrade purity.Cell Culture and myo-[3HJInositol Labeling. The HIRc-B cells (7,8) were generously supplied by Donald McClain (University of Alabama, Birmingham). Cells were incubated at 37°C in air containing 5% CO2 at 90o relative humidity. Before labeling, cells were grown to =2 x 104 per cm2 in 10-cm-diameter dishes in Dulbecco's modified Eagle's medium (DMEM; GIBCO/BRL) supplemented to contain 10% fetal bovine serum (GIBCO/BRL) and 100 nM methotrexate (9). The medium in each dish was replaced with 7 ml of inositol-free DMEM containing 10%o dialyzed fetal bovine serum, 100 nM methotrexate, and myo-[1,2-3H]inositol (22 ,uCi/ml; 46.0 Ci/mmol, DuPont/New England Nuclear; 1 Ci = 37 GBq). After incubation for 24 hr, the cells were serum-starved by replacing the medium with 7 ml of inositolfree DMEM supplemented with human transferrin (5 Mg/ml), methotrexate (100 nM), and myo-[3H]inositol (3 uCi/ml) and incubating for an additional 24 hr.Insulin St...

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Identification and partial characterization of inositol; NAD⁺ epimerase and inosose: NAD(P)H reductase from the fat body of the American cockroach, Periplaneta americana

Cited by 45 publications

References 19 publications

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Genetic Modification of Bacillus subtilis for Production of d - chiro -Inositol, an Investigational Drug Candidate for Treatment of Type 2 Diabetes and Polycystic Ovary Syndrome

Insulin stimulates the biosynthesis of chiro-inositol-containing phospholipids in a rat fibroblast line expressing the human insulin receptor.

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Identification and partial characterization of inositol; NAD+ epimerase and inosose: NAD(P)H reductase from the fat body of the American cockroach, Periplaneta americana

Cited by 45 publications

References 19 publications

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Genetic Modification of Bacillus subtilis for Production of d - chiro -Inositol, an Investigational Drug Candidate for Treatment of Type 2 Diabetes and Polycystic Ovary Syndrome

Insulin stimulates the biosynthesis of chiro-inositol-containing phospholipids in a rat fibroblast line expressing the human insulin receptor.

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Identification and partial characterization of inositol; NAD⁺ epimerase and inosose: NAD(P)H reductase from the fat body of the American cockroach, Periplaneta americana