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• W3125031975 endingPage "4152" @default.
• W3125031975 startingPage "4129" @default.
• W3125031975 abstract "Leishmania has a remarkable ability to proliferate under widely fluctuating levels of essential nutrients, such as glucose. For this, the parasite is heavily dependent on its gluconeogenic machinery. One perplexing aspect of gluconeogenesis in Leishmania is the lack of the crucial gene for pyruvate carboxylase (PC). PC‐catalyzed conversion of pyruvate to oxaloacetate is a key entry point through which gluconeogenic amino acids are funneled into this pathway. The absence of PC in Leishmania thus raises question about the mechanism of pyruvate entry into the gluconeogenic route. In the present study, we report that this task is accomplished in Leishmania major through a novel functional partnership between its mitochondrial malic enzyme (LmME) and carbonic anhydrase 1 (LmCA1). Using a combination of pharmacological inhibition studies with genetic manipulation, we show that both of these enzymes are necessary for promoting gluconeogenesis and supporting parasite growth under glucose‐limiting conditions. Functional cross‐talk between LmME and LmCA1 was evident when it was observed that the growth retardation caused by inhibition of any one of these enzymes could be protected to a significant extent by overexpressing the other enzyme. We also found that, although LmCA1 exhibited constitutive expression, the LmME protein level was strongly upregulated under low glucose conditions. Notably, both LmME and LmCA1 were found to be important for survival of Leishmania amastigotes within host macrophages. Taken together, our results indicate that LmCA1 by virtue of its CO 2 concentrating ability stimulates LmME‐catalyzed pyruvate carboxylation, thereby driving gluconeogenesis through the pyruvate–malate–oxaloacetate bypass pathway. Additionally, our study establishes LmCA1 and LmME as promising therapeutic targets." @default.
• W3125031975 created "2021-02-01" @default.
• W3125031975 creator A5028304438 @default.
• W3125031975 creator A5043595661 @default.
• W3125031975 creator A5062553832 @default.
• W3125031975 creator A5081334142 @default.
• W3125031975 date "2021-02-28" @default.
• W3125031975 modified "2023-09-25" @default.
• W3125031975 title "Functional partnership between carbonic anhydrase and malic enzyme in promoting gluconeogenesis in <i>Leishmania major</i>" @default.
• W3125031975 cites W1491912808 @default.
• W3125031975 cites W1505164064 @default.
• W3125031975 cites W1531782279 @default.
• W3125031975 cites W1597308548 @default.
• W3125031975 cites W1775749144 @default.
• W3125031975 cites W1787918626 @default.
• W3125031975 cites W1811132283 @default.
• W3125031975 cites W1924798630 @default.
• W3125031975 cites W1947652441 @default.
• W3125031975 cites W1963542761 @default.
• W3125031975 cites W1967855615 @default.
• W3125031975 cites W1971619507 @default.
• W3125031975 cites W1974261306 @default.
• W3125031975 cites W1975684232 @default.
• W3125031975 cites W1975858959 @default.
• W3125031975 cites W1979080877 @default.
• W3125031975 cites W1979661372 @default.
• W3125031975 cites W1983044486 @default.
• W3125031975 cites W1985233399 @default.
• W3125031975 cites W1985483420 @default.
• W3125031975 cites W1987096190 @default.
• W3125031975 cites W1987166450 @default.
• W3125031975 cites W1990660943 @default.
• W3125031975 cites W1992271667 @default.
• W3125031975 cites W1992412341 @default.
• W3125031975 cites W1997455728 @default.
• W3125031975 cites W2000045912 @default.
• W3125031975 cites W2008053134 @default.
• W3125031975 cites W2011553235 @default.
• W3125031975 cites W2011801069 @default.
• W3125031975 cites W2017699535 @default.
• W3125031975 cites W2032045884 @default.
• W3125031975 cites W2037456641 @default.
• W3125031975 cites W2047817180 @default.
• W3125031975 cites W2055715126 @default.
• W3125031975 cites W2060724686 @default.
• W3125031975 cites W2064371114 @default.
• W3125031975 cites W2070283622 @default.
• W3125031975 cites W2075878636 @default.
• W3125031975 cites W2075915930 @default.
• W3125031975 cites W2076598575 @default.
• W3125031975 cites W2077945404 @default.
• W3125031975 cites W2080889972 @default.
• W3125031975 cites W2086208209 @default.
• W3125031975 cites W2089047063 @default.
• W3125031975 cites W2090009771 @default.
• W3125031975 cites W2091788742 @default.
• W3125031975 cites W2092901567 @default.
• W3125031975 cites W2094920220 @default.
• W3125031975 cites W2097325341 @default.
• W3125031975 cites W2103110974 @default.
• W3125031975 cites W2107915297 @default.
• W3125031975 cites W2111127373 @default.
• W3125031975 cites W2113234234 @default.
• W3125031975 cites W2116368430 @default.
• W3125031975 cites W2121297416 @default.
• W3125031975 cites W2122094250 @default.
• W3125031975 cites W2122413738 @default.
• W3125031975 cites W2123139638 @default.
• W3125031975 cites W2127914291 @default.
• W3125031975 cites W2132848975 @default.
• W3125031975 cites W2134883783 @default.
• W3125031975 cites W2140993831 @default.
• W3125031975 cites W2144798903 @default.
• W3125031975 cites W2151406110 @default.
• W3125031975 cites W2151770702 @default.
• W3125031975 cites W2152770371 @default.
• W3125031975 cites W2158501592 @default.
• W3125031975 cites W2173122004 @default.
• W3125031975 cites W2254441091 @default.
• W3125031975 cites W2288446565 @default.
• W3125031975 cites W2326389904 @default.
• W3125031975 cites W2408220061 @default.
• W3125031975 cites W2415945663 @default.
• W3125031975 cites W2527194821 @default.
• W3125031975 cites W2534655250 @default.
• W3125031975 cites W2569462802 @default.
• W3125031975 cites W2579064583 @default.
• W3125031975 cites W2611980624 @default.
• W3125031975 cites W2617445492 @default.
• W3125031975 cites W2767248253 @default.
• W3125031975 cites W2805343660 @default.
• W3125031975 cites W2899346577 @default.
• W3125031975 cites W2981497229 @default.
• W3125031975 cites W3029697906 @default.
• W3125031975 cites W4211073781 @default.
• W3125031975 doi "https://doi.org/10.1111/febs.15720" @default.
• W3125031975 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33464696" @default.
• W3125031975 hasPublicationYear "2021" @default.

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