Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Genetic improvement of soybeans in Brazil: South and Midwest regions

Abstract: Soybean [Glycine max (L.) Merril] is one of the main crops produced worldwide, and on-farm yields have increased considerably in the last decades in Brazil. We evaluated the genetic gain for agronomic, phenological, and end-use quality traits in 29 cultivars in the South Region, and in 38 cultivars in the Midwest Region in Brazil, released from 1966 to 2011. Field trials were conducted in Macroregions 1, 2, and 4, in 2016?2017, 2017?2018, and 2018?2019 crop seasons. The best linear unbiased predictors (BLUP) of the cultivars were obtained for each trait using a linear model. The BLUPs were regressed with the year of release using linear and quadratic regression models. The rates of genetic gain for seed yield ranged from 11.98 to 15.31 kg ha?1 yr?1 (0.33 to 0.42% yr?1) in the South Region, and from 13.58 to 21.84 kg ha?1 yr?1 (0.47 to 0.77% yr?1) in the Midwest Region. New cultivars presented taller plants and more seed oil content, oil and protein yield, and lower seed weight, days to flowering, days to maturity, and seed protein content than old cultivars in the South Region, although with differences between the Macroregions. In the Midwest Region, new cultivars showed higher seed oil content, oil and protein yield, and lower bottom pod height and seed protein content than old cultivars. Our results showed that breeding programs have been efficient to improve soybean yield and other traits across the years, without yield plateaus in sight