A simple metabolic flux balance analysis of biomass and bioethanol production in Saccharomyces cerevisiae fed-batch cultures

Production of Saccharomyces cerevisiae yeast for applications in the food industry or in bioethanol production still presents important techno-economic challenges as an industrial bioprocess. Mathematical modeling of cellular metabolism in biological production usually improves process yields, though for industrial applications, the model should be as simple as possible in order to sustain model usefulness and technical feasibility. A comparative analysis between a black box description and a simple metabolic network accounting for the main metabolic events involved in yeast growth and bioethanol production is proposed here. In both cases, a thorough analysis of reaction rates allowed for the ethanol concentrations produced in fed-batch yeast cultures, although our results showed more accurate estimations with the metabolic flux balance methodology. Moreover, an interpretation of the yeast physiological state in fed-batch cultures at different glucose feed concentrations was accomplished by means of a stoichiometric analysis linked to the simplified metabolic network. The results confirmed that increasing glucose uptake rates, controlled mainly by the glucose concentration in the input flow, produced an up-regulation in reductive catabolism, resulting in higher ethanol excretion. The biomass production relied mostly on oxidative catabolism, which is controlled by the glucose and oxygen uptake rates. Thus, ethanol or biomass production is strongly dependent on the physiological state of yeast in the culture, which can be inferred from a suitable metabolic flux balance approach

A Higher Fructose Intake Is Associated with Greater Albuminuria in Subjects with Type 2 Diabetes Mellitus

The aim of this single center cross-sectional study was to investigate the association between fructose intake and albuminuria in subjects with type 2 diabetes mellitus (T2DM). This is a single center cross-sectional study. One hundred and forty-three subjects with T2DM were recruited from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. The median daily fructose intake was estimated with a prospective food registry during 3 days (2 week-days and one weekend day) and they were divided into low fructose intake (<25 g/day) and high fructose intake (≥ 25 g/day). Complete clinical and biochemical evaluations were performed, including anthropometric variables and a 24-hour urine collection for albuminuria determination. One hundred and thirty-six subjects were analyzed in this study. We found a positive significant association between daily fructose intake and albuminuria (ρ= 0.178, p=0.038) in subjects with type 2 diabetes mellitus. Other variables significantly associated with albuminuria were body mass index (BMI) (ρ= 0.170, p=0.048), mean arterial pressure (MAP) (ρ= 0.280, p=0.001), glycated hemoglobin (A1c) (ρ= 0.197, p=0.022), and triglycerides (ρ= 0.219, p=0.010). After adjustment for confounding variables we found a significant and independent association between fructose intake and albuminuria (β= 13.96, p=0.006). We found a statistically significant higher albuminuria (60.8 [12.8-228.5] versus 232.2 [27.2-1273.0] mg/day, p 0.002), glycated hemoglobin (8.6±1.61 versus 9.6±2.1 %), p= 0.003, and uric acid (6.27±1.8 versus 7.2±1.5 mg/dL), p=0.012, in the group of high fructose intake versus the group with low fructose intake, and a statistically significant lower creatinine clearance (76.5±30.98 mL/min versus 94.9±36.8, p=0.014) in the group with high fructose intake versus the group with low fructose intake. In summary we found that a higher fructose intake is associated with greater albuminuria in subjects with T2DM