Glucose uptake stimulatory effect of 4-hydroxypipecolic acid by increased GLUT 4 translocation in skeletal muscle cells

Gutta, Naresh; Jaiswal, Natasha; Sukanya, P.; Srivastava, Arvind K.; Tamrakar, Akhilesh K.; Narender, Tadigoppula

doi:10.1016/j.bmcl.2012.06.101

Cited by 23 publications

(12 citation statements)

References 21 publications

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“…It was also reported to be a relatively selective agonist of an Nmethyl-D-aspartate receptor subtype prevalently found in the mouse cortex (32). Additionally, trans-4-L-HyPip has antidiabetic and antioxidative effects in mice (33) and stimulated glucose uptake and glucose transporter-4 translocation from an intracellular location to the cell surface in skeletal muscle cells (34). Moreover, trans-4-L-HyPip has been found to be present as a component of various bioactive compounds.…”

Section: Discussionmentioning

confidence: 98%

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Hibi

Mori

Miyake

et al. 2016

Appl Environ Microbiol

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Hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. We have found a novel hydroxylating enzyme with activity toward L-pipecolic acid (L-Pip) in a filamentous fungus, Fusarium oxysporum c8D. The enzyme L-Pip trans-4-hydroxylase (Pip4H) of F. oxysporum (FoPip4H) belongs to the Fe(II)/␣-ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio-and stereoselective hydroxylation of L-Pip, and produces optically pure trans-4-hydroxy-L-pipecolic acid (trans-4-L-HyPip). Amino acid sequence analysis revealed several fungal enzymes homologous with FoPip4H, and five of these also had L-Pip trans-4-hydroxylation activity. In particular, the homologous Pip4H enzyme derived from Aspergillus nidulans FGSC A4 (AnPip4H) had a broader substrate specificity spectrum than other homologues and reacted with the L and D forms of various cyclic and aliphatic amino acids. Using FoPip4H as a biocatalyst, a system for the preparative-scale production of chiral trans-4-L-HyPip was successfully developed. Thus, we report a fungal family of L-Pip hydroxylases and the enzymatic preparation of trans-4-L-HyPip, a bioactive compound and a constituent of secondary metabolites with useful physiological activities.H ydroxypipecolic acids (HyPips) are naturally occurring sixmembered heterocyclic hydroxy amino acids that are widely distributed in nature. For instance, 4-hydroxy-, 5-hydroxy-, and 4,5-dihydroxypipecolic acids have been found in various members of the plant family (1-4). Likewise, 5-hydroxypipecolic acid was found to be present in mammalian brain and blood (5). HyPips are also components of some peptide antibiotics, terpenoids, and alkaloids, for example, Thus, the enzymatic hydroxylation of L-Pip was achieved as a side reaction of L-proline hydroxylase. To date, specific L-Piphydroxylating enzymes have not been reported, despite the fact that HyPips are important metabolites found in plants and mammals. In the present study, we identified and characterized L-Pip hydroxylases broadly conserved in some filamentous fungi. We found that the newly discovered L-Pip hydroxylases were particularly suitable biocatalysts for the asymmetric hydroxylation of cyclic amino acids, such as pipecolic acids and prolines. Moreover, the widespread distribution of genes encoding L-Pip hydroxylases indicates some important physiological roles of fungal secondary metabolites related to trans-4-L-HyPip. MATERIALS AND METHODSStrains and culture. Microorganisms isolated from soil and plant samples were cultured in GP medium comprised of 0.15% (wt/vol) KH 2 PO 4 , 0.05% (wt/vol) K 2 HPO 4 , 0.1% (wt/vol) NH 4 Cl, 0.03% (wt/vol) MgSO 4 ·7H 2 O, 0.01% (wt/vol) yeast extract, 0.025% (wt/vol) glucose, and 0.1% (wt/vol) L-Pip (pH 7.0) and grown at 28°C with shaking. Escherichia coli JM109 and Rosetta2(DE3) (Novagen, WI, USA) were used as host strains for the overexpression of the recombinant enzymes and cultured at 28°C in LB medium, comprised of 1% (wt/v...

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Section: Discussionmentioning

confidence: 98%

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Hibi

Mori

Miyake

et al. 2016

Appl Environ Microbiol

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“…27−29) In addition, a structural analog of Pip, 4-hydroxypipecolic acid, regulates glucose metabolism. 30,31) The effects of 2-AA and Pip on protein Notes: (A) The rate of protein synthesis was evaluated by puromycin-labeled peptides in myotubes treated with 10 mM Lys, 10 mM Leu, or 100 nM insulin for 30 min. (B) The rate of protein synthesis was evaluated by puromycin-labeled peptides in myotubes treated with 10 mM Lys or 10 mM Ala for 30 min.…”

Section: Discussionmentioning

confidence: 99%

Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes

Sato

Ito

Nagasawa

2016

Bioscience, Biotechnology, and Biochemistry

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We previously showed that L-lysine (Lys) and a metabolite of Lys, L-saccharopine, suppressed autophagic proteolysis in C2C12 myotubes. However, the effects of other metabolites of Lys on protein turnover were unknown. We here investigated the effect of the Lys metabolites, L-2-aminoadipic acid (2-AA) and L-pipecolic acid (Pip), on protein turnover in C2C12 myotubes. 2-AA suppressed myofibrillar protein degradation evaluated by the 3-methylhistidine and autophagy activity evaluated by light chain 3-II at lower concentration (100 μM) than did Lys. On the other hand, Pip stimulated the mammalian target of rapamycin signaling activity. Additionally, 100 μM Pip significantly increased the rates of protein synthesis whereas 100 μM Lys had no effect. These results indicate that in C2C12 myotubes, 2-AA could suppress autophagy and Pip could stimulate the rates of protein synthesis, and these metabolites may contribute to exert effect of Lys on protein turnover.

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“…Increasing evidence suggests that impaired translocation of GLUT4 is linked to reduced glucose utilization in the muscle of insulin-resistant and type 2 patients. Therefore, this protein may serve as a therapeutic target for diabetes (Naresh et al, 2012;Zhang et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Antidiabetic activity of perylenequinonoid-rich extract from Shiraia bambusicola in KK-Ay mice with spontaneous type 2 diabetes mellitus

Zhao

Xiong

et al. 2016

Journal of Ethnopharmacology

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Glucose uptake stimulatory effect of 4-hydroxypipecolic acid by increased GLUT 4 translocation in skeletal muscle cells

Cited by 23 publications

References 21 publications

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans -4-Hydroxylation of l -Pipecolic Acid

Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes

Antidiabetic activity of perylenequinonoid-rich extract from Shiraia bambusicola in KK-Ay mice with spontaneous type 2 diabetes mellitus

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