A mechanistic model of mammary gland metabolism in the lactating cow

Abstract

The objective of this experiment was to construct a model of mammary gland metabolism adequate to simulate in-vivo and in-vitro data obtained from studies of bovine mammary glands. Equations describing fluxes to and from individual metabolite pools and fluxes of individual carbons within each metabolite pool were included. These equations were based primarily on the Michaelis-Menten form, e.g. saturation kinetics. Equations describing the flow of individual carbons were included to allow simulation of radiotracer experiments. Steady state fluxes were set using in-vivo data collected from arteriovenous difference studies conducted on lactating Holstein cows. Model behavior was compared to in-vitro observations published previously. Behavior analyses indicated that, in general, equation forms were appropriate and that no additional equations were required. Equations describing uptake of acetate and lactate from circulation or media were under-responsive to nutrient concentrations as concentrations increased. Radiolabel incorporation into citrate and fatty acids when glucose or lactate was used as radiotracer and into glyceride-glycerol when acetate or lactate was used as radiotracer was less than observed previously. Sensitivity analyses indicated that capacities to convert pyruvate to mitochondrial acetyl-CoA, pyruvate to oxaloacetate, malate to glycerol-3-phosphate, and citrate to cytosolic acetyl-CoA must be increased to simulate the radiotracer data of Forsberg et al. (Forsberg N. E., Baldwin, R. L. & Smith, N. E. (1984). Roles of acetate and its interactions with glucose and lactate in cow mammary tissue. J. Dairy Sci., 67, 2247–2254; Forsberg, N. E., Baldwin, R. L. & Smith N. E. (1985). Roles of lactate and its interactions with lactate in maintenance and biosynthesis in bovine mammary tissue. J. Dairy Sci., 68, 2250–2256; Forsberg, N. E., Baldwin, R. L. & Smith, N. E. (1985). Roles of glucose and its interactions with acetate in maintenance and biosynthesis in bovine mammary tissue. J. Dairy Sci., 68, 2544–2549). Date related to acetate and lactate metabolism appear to be adequate to define parameters associated with these equations. Data related to glucose metabolism apparently are not adequate to define equations associated with glucose metabolism.