The effect of histidine and cysteine on zinc influx into rat and human erythrocytes.

Abstract

1. The effect of histidine and cysteine on the initial rate of zinc influx into rat and human erythrocytes in the presence of bovine serum albumin has been investigated. 2. The L-enantiomers of both amino acids promoted zinc influx into rat erythrocytes in a dose-dependent manner. L-Histidine, but not L-cysteine, also promoted zinc uptake into human erythrocytes. D-Histidine did not promote zinc uptake in either rat or human erythrocytes. In rat erythrocytes D-cysteine was significantly less effective than L-cysteine.3. The stimulation of zinc influx into rat erythrocytes by 20 mM L-histidine was approximately 4 1 times that seen with human erythrocytes. 4. The influx of zinc in the presence of varying concentrations of L-histidine was linearly related to the calculated concentration of the zinc-bis-histidine complex but not to that of the zinc-mono-histidine complex or the free ionic zinc concentration. 5. These results are discussed in relation to the nature of the transport mechanisms involved.

3H-l-histidine and 65Zn2+ are cotransported by a dipeptide transport system in intestine of lobsterHomarus americanus

“…An additional zinc transport process that has received attention in recent years is the apparent coupling of the metal with specific amino acids such as L-histidine and L-cysteine (Horn et al, 1995;Horn and Thomas, 1996;Glover and Hogstrand, 2002a,b;Glover et al, 2003). These latter studies have suggested processes whereby luminal zinc complexes with two amino acids in solution in a bis-complex (Zn- [His] 2 ) and the combination is transported as a unit across the cellular membrane.…”

“…Fig.·8 indicates a significant (P<0.01) and mixed inhibitory effect of the dipeptide on zincstimulated 3 H-L-histidine transport, suggesting that the dipeptide and amino acid interact with each other for the cotransport process with zinc. If this is the case, then the cotransport process transferring both L-histidine and zinc across lobster intestine likely accommodates two L-histidine amino acids linked to the zinc cation in a bis-complex, as described by Horn et al (1995) and Horn and Thomas (1996), and in this configuration sufficiently resembles dipeptides in solution to utilize a transport system that normally would accommodate two amino acids linked by a peptide bond. The dipeptide transporter (e.g.…”

Epithelia & Membrane Transport

“…Histidine is capable of promoting zinc uptake into human erythrocytes under incubation conditions where the free ionic zinc concentration is kept low. This stimulation correlates better with the calculated concentration of zinc bis-histidine rather than zinc mono-histidine (Horn et al 1995). Cadmium (Horn & Thomas, 1996) and copper (Horn & Thomas, 1997) are able to inhibit histidine-stimulated zinc uptake, and if the studies are carried out at high (40 mM) histidine concentrations, which ensures that most of the metal is in the bis-histidine form, the calculated concentrations of the bis-histidine complexes of cadmium, copper and zinc corresponding to 50 % inhibition of 65Zn uptake (Ki) are similar.…”

Epithelia & Membrane Transport

“…(1998) Zinc binds strongly to proteins and thus the free ionic zinc concentration under physiological conditions is very low. Histidine stimulates 65Zn uptake by human erythrocytes when they are incubated in the presence of a suitable metal chelating agent such as BSA (Horn et al 1995). This histidine stimulation of zinc uptake is saturable and stereospecific for the L-enantiomer, which suggests that a binding step is involved in the uptake process.…”

“…This blood was drawn with local ethical committee Journal of Physiology (1998) 513.P approval and coagulation was prevented by the addition of EDTA (10 mM). 65Zn uptake into washed erythrocytes was determined as described previously (Horn et al 1995). When the 12 min uptakes were plotted against the calculated concentrations of the various forms of 65Zn, little correlation was seen with L-histidine, free ionic zinc or zinc monohistidine, but there was a good correlation between zinc uptake and the calculated zinc bis-histidine concentration (Fig.…”