Trace metal requirements in total parenteral nutrition. Part 6. A quantitative study of the copper(II)histidine ternary complexes with leucine,glutamic acid,methionine, tryptophan and alanine,and final evaluation of the daily doses of copper and zinc specific to a nutritive mixture of a given composition

A computer-based approach was previously developed which made it possible to interpret the origin of the trace metal extra-losses induced by total parenteral nutrition (TPN) on a quantitative basis. The TPN-induced abnormal excretions of zinc and copper have been attributed to the enhanced mobilization of these metal ions into their plasma low molecular weight fraction by specific components of the nutritive solution, the mode of excretion (urinary for zinc/biliary for copper) being dictated by the electrical charge of the prevailing complexes. This implies that the trace metal needs during TPN must depend on the composition of the infusate.It was thus proposed that every nutritive solution should contain total trace metal in such an amount that the corresponding free concentration be the same as that pertaining to normal blood plasma. In this way, the metal losses would not occur at the expense of the patient's body reserve.Nevertheless, two conditions must be fulfilled before reliable doses can be calculated for a given nutritive mixture: (i) precise free metal ion concentrations in normal blood plasma must be assessed, (ii) a computer-based reliable distribution of each metal ion in the nutritive solution must be obtained. Now, the reliability of the involved simulation model directly depends on that of the equilibrium constants of the predominant complexes. A series of determinations was thus successively carried out for zinc and copper until a realistic degree of reliability (over 80%) was reached.The present paper focuses on the determination of the formation constants of the mixed-ligand complexes formed by copper and histidine with five amino acids prevailing in the nutritive mixture under study, which brings the degree of reliability of the copper distribution up to 84%.The final estimation of the zinc and copper absolute doses for the nutritive solution chosen as a reference is discussed with regard to the limitations of the present approach for which a number of applications are suggested.