Inhibition of sorbitol dehydrogenase by nucleosides and nucleotides

Lindstad, Rune I.; Teigen, Knut; Skjeldal, Lars

doi:10.1016/j.bbrc.2013.04.081

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…SORD is a homotetramer of 38-kDa subunits and is widely expressed in mammalian tissues (4,11,12). It is the second enzyme of the two-step polyol pathway, in which aldose reductase converts glucose into sorbitol, a relatively nonmetabolizable sugar, which is then oxidized to fructose by SORD ( Fig.…”

Section: Loss Of Sord Enzymatic Activity and Increased Serum Fasting mentioning

confidence: 99%

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Cortese¹,

Zhu²,

Züchner³

et al. 2020

Nat Genet

122

109

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Here we demonstrate biallelic mutations in sorbitol dehydrogenase (SORD) as the most frequent recessive form of hereditary neuropathies. We identified 45 cases from 38 families across multiple ethnicities, carrying a particular nonsense mutation in SORD, c.753delG; p.Ala253GlnfsTer27, either in homozygous or compound heterozygous state with a second variant. With an allele frequency of 0.004 in healthy controls, the p.Ala253GlnfsTer27 variant represents one of the most common pathogenic alleles in humans. SORD is an enzyme that converts sorbitol into fructose, in the two-step polyol pathway that has been implicated in diabetic neuropathy. In patient-derived fibroblasts, we find a complete loss of SORD protein as well as increased intracellular sorbitol. Also, serum fasting sorbitol level was over 100 times higher in patients homozygous for the p.Ala253GlnfsTer27 mutation compared to healthy individuals. In Drosophila, we show that loss of SORD orthologues causes synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a potentially treatable cause in a significant fraction of patients with inherited neuropathies and may contribute to a better understanding of the pathophysiology of diabetic neuropathy.

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Section: Loss Of Sord Enzymatic Activity and Increased Serum Fasting mentioning

confidence: 99%

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Cortese¹,

Zhu²,

Züchner³

et al. 2020

Nat Genet

122

109

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“…The mode of inhibition of sorbitol dehydrogenase by lime fruit extract was performed according to the method described by Lindstad et al [14]. In one set of tubes, the reaction mixture contained 100 mM tris‐HCl buffer (pH 9.0), 0.5 mM NAD + , 50 µL of 100 µg/mL sorbitol dehydrogenase, sorbitol (100–500 mM) and 50 µg/mL grapefruit extract.…”

Section: Methodsmentioning

confidence: 99%

Citrus aurantifolia(Christm.) Swingle (lime) Fruit Extract Inhibits the Activities of Polyol Pathway Enzymes

Kazeem

Bankole

Oladokun

et al. 2020

eFood

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Diabetes mellitus is associated with several complications, which may result from one or more factors including increased flux of polyol pathway. This study evaluated the inhibitory potential of four citrus fruits namely Citrus paradisi Macfad. (grape), Citrus limon (L.) Osbeck (lemon), Citrus aurantifolia (Christm.) Swingle (lime) and Citrus sinensis (L.) Osbeck (orange), on the activities of aldose reductase and sorbitol dehydrogenase -the two enzymes that mediate the polyol pathway. This is determined by incubating citrus extracts with appropriate enzymes and substrates. Fruit extract with the lowest half maximal inhibitory concentration (IC 50 ) was used to assess the mode of inhibition of the enzymes by preparing Lineweaver-Burk plot. Citrus fruits tested inhibited sorbitol dehydrogenase more than aldose reductase, which resulted in lowered IC 50 values. Of all the citrus fruits tested, lime fruit extract displayed potent inhibition of aldose reductase (IC 50 : 138.66 µg/mL) and sorbitol dehydrogenase (IC 50 : 47.21 µg/mL). Kinetic studies also revealed that lime fruit extract inhibited the activities of both enzymes in a competitive manner. In conclusion, the inhibition of the polyol pathway enzymes by the lime fruit extract may be attributed to the presence of phytochemicals such as flavonoids and limonoids.

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“…Inhibition of sorbitol dehydrogenase activity by different concentrations (125 -1000 µg/mL) of A. repens extracts was evaluated using the modified procedure of Lindstad et al 16…”

Section: Sorbitol Dehydrogenase Inhibitory Assaymentioning

confidence: 99%

Ethanol Extract of Aristolochia repens Mill. Stem Inhibits the Activities of some Enzymes Targeted in the Treatment of Diabetes Mellitus

2021

TJNPR

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Aristolochia repens which is known as "Ako-igun" by the "Yoruba" speaking people of Nigeria and "Dumandutsee" in the Northern part of Nigeria, is a climbing bushy plant originally native to tropical America but now cultivated in most countries in West Africa. 8 The plant is used in the management of various ailments in many regions of the world. 9 The root is used in Southwestern Nigeria to treat asthma and diarrhea, 10 while the stem is used for the management of diabetes mellitus and complications associated with it. 11 Phytochemical analysis revealed the presence of different types of aristolochic acid as the main bioactive compound in this plant. These include aristolochic acid I, aristolochic acid II, and aristolochic acid IV. 12 Despite the various reports on this plant used in treating several diseases, there is a scarcity of information on its hypoglycemic property as well as modulatory potential on relevant enzymes linked to diabetes mellitus. This study evaluated α-amylase, α-glucosidase, and sorbitol dehydrogenase inhibitory activity of A. repens stem extracts. The mode of inhibition of the targeted enzymes was also determined, to understand the probable mechanisms of action of the extracts in eliciting their antidiabetic activities. Materials and Methods Plant material The stem of A. repens was procured from the traditional medicine store in Idumota, Lagos, Nigeria. The sample was confirmed by Dr. A. B. Kadiri, a taxonomist at the University of Lagos, Nigeria, and the voucher sample with reference number LUH 8376 was deposited in the herbarium. Chemicals and reagents Experimental grade A. oryzae α-amylase, S. cerevisiae α-glucosidase, D-sorbitol, NADH, sorbitol dehydrogenase, Tris buffer, Acarbose, maltose, and soluble starch (extra pure) were purchased from Sigma

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Inhibition of sorbitol dehydrogenase by nucleosides and nucleotides

Cited by 9 publications

References 33 publications

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Citrus aurantifolia(Christm.) Swingle (lime) Fruit Extract Inhibits the Activities of Polyol Pathway Enzymes

Ethanol Extract of Aristolochia repens Mill. Stem Inhibits the Activities of some Enzymes Targeted in the Treatment of Diabetes Mellitus

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