Modeling portal-drained viscera and liver fluxes of essential amino acids in dairy cows

Abstract

The objective of this work was to predict essential amino acid (EAA) use and release by the portal-drained viscera (PDV) and liver of dairy cows. Previously derived equations were tested using data assembled from the literature, refit to the data, and modifications were undertaken to determine the best model for each EAA. The refitted model has the same structure as the original equations but is parameterized using a database of group means, as the original equations were derived using a single study with individual cow data and found to be biased. The PDV clearance model predicted portal vein concentrations given inputs of absorbed and arterial fluxes of EAA with root mean squared errors (RMSE) ranging from 3.3 to 12.1% of the observed means, and concordance correlation coefficients (CCC) ranging from 0.86 to 0.99 when using previously reported parameters. The reparameterized model generated from the assembled data set resulted in predictions of EAA portal vein concentrations with RMSE ranging from 3.2 to 8.6% and CCC ranging from 0.93 to 1.00. Slope bias ranged from 12.4 to 55.3% of mean squared errors and was correlated with arterial EAA concentrations. Modifying the model to allow rate constants to vary as a function of arterial EAA concentrations reduced slope bias, resulting in RMSE ranging from 1.9 to 6.5% and CCC from 0.97 to 1.00. Alternatively, splitting the model to account for use of EAA from absorption separately from arterial use resulted in poorer predictions and biologically infeasible parameter estimates. The liver clearance model predicted hepatic vein concentrations from arterial and portal vein input fluxes with RMSE across EAA ranging from 1.9 to 6.8% and CCC ranging from 0.97 to 1.00 when using reported parameters. The reparameterized model generated from the assembled data set resulted in predictions of EAA hepatic vein concentrations with RMSE ranging from 1.9 to 6.7% and CCC ranging from 0.97 to 1.00. Significant slope bias was present for Arg, His, Lys, Phe, Thr, and Val. Altering the model to represent the clearance rate constant as a function of arterial concentrations resulted in RMSE ranging from 1.8 to 6.5% and CCC ranging from 0.97 to 1.00. The combination of PDV and liver clearance models provided predictions of total splanchnic use similar to those of an empirical model representing splanchnic use as a fractional proportion of absorption that had RMSE ranging from 3.0 to 8.6% and CCC ranging from 0.95 to 0.99, with significant slope bias for the majority of EAA.

The market for amino acids: understanding supply and demand of substrate for more efficient milk protein synthesis

“…Blood AA concentrations are determined by the rate of appearance of individual AA into the circulation, which is in turn the result of AA absorption from the lumen of the intestine minus retention by the splanchnic tissues. However, arterial blood supplies about 80% of the AA removed by splanchnic tissues [58], such that the peripheral tissues' extraction of AA largely determines the supply to the splanchnic tissues. Independent of the amount of AA absorbed, changes in local blood flow control partitioning of those AA between peripheral tissues, and can affect the supply of AA to the mammary glands [59].…”

“…Estimates indicate that splanchnic tissues sequester half of the essential AA absorbed from the small intestine [58]. However, in addition to AA absorbed from the intestine, splanchnic tissues receive AA in arterial blood, which represent about 80% of the total AA flux to the tissue bed [8].…”

“…fixed) extraction efficiencies of AA by both the PDV and the liver [111,112]. A recent revision of those models revealed that similar to the mammary glands, PDV utilization of individual AA are better represented with saturable functions, suggesting a fixed requirement for AA [58]. Conversely, liver extraction of Arg, His, Lys, Met and Phe were best represented by non-linear functions, with extraction efficiencies positively related to AA supply [58].…”

“…A recent revision of those models revealed that similar to the mammary glands, PDV utilization of individual AA are better represented with saturable functions, suggesting a fixed requirement for AA [58]. Conversely, liver extraction of Arg, His, Lys, Met and Phe were best represented by non-linear functions, with extraction efficiencies positively related to AA supply [58]. This means that the more of these AA the liver receives, the more it clears, in line with the liver's role to dispose of excess absorbed nitrogen.…”

“…Cantalapiedra-Hijar and collaborators assessed how dietary energy from starch vs fiber impacts hepatic extraction of AA at 12% and 16.5% crude protein (CP) diets in lactating Jersey cows [102]. In line with the most recent fitting of Hanigan's model [58], dietary CP but not energy source affected hepatic extraction of most AA. Conversely, dietary starch, probably through an insulin-mediated effect, increased essential AA removal by the mammary glands in these same cows [103], resulting in lower recycling and greater release of absorbed AA by splanchnic tissues.…”