Human fetal endothelial cells acquire Zinc(II) from both the protein bound and nonprotein bound pools in serum

To help determine physiologically important routes by which zinc (Zn) is acquired by human fetal vascular endothelium, the authors incubated cultured umbilical vein endothelial cells with⁶⁵Zn(II)-tracer labeled human fetal whole serum, ultrafiltrate (containing low molecular mass serum zinc complexes), and dialyzed serum (containing protein-bound zinc). Zinc from whole serum and from both serum fractions entered a rapidly labeled cellular compartment removable by edetic acid (EDTA), representing Zn bound to the outside cell surface, and accumulatively, an EDTA-resistant compartment’probably largely internalized Zn. Entry of Zn into the EDTA-resistant pool from both serum fractions was strongly temperature-dependent, and was not via the EDTA-sensitive pool. Entry from the ultrafiltrate was resolvable into high affinity saturable, and non-(or hardly-) saturable components. Transfer from the dialyzed serum fraction was not significantly saturable, but only partially accounted for by nonspecific pinocytosis. Thus, Zn is obtained by fetal vascular endothelium partly from low molecular mass serum species, probably through at least one carrier-mediated membrane transport system; but also from Zn complexed with serum protein, via at least one metabolism-related route.     

Zinc uptake across the apical membrane of freshwater rainbow trout intestine is mediated by high affinity, low affinity, and histidine-facilitated pathways

Zinc is both a vital nutrient and an important toxicant to aquatic biota. In order to understand the interplay between nutrition and toxicity, it will be important to determine the mechanisms and the factors that regulate zinc uptake. The mechanism of apical intestinal Zn(II) uptake in freshwater rainbow trout and its potential modification by the complexing amino acid histidine was investigated using brush-border membrane vesicles (BBMVs). Following characterisation of the BBMV preparation, zinc uptake in the absence of histidine was both time- and concentration-dependent and consisted of two components. A saturable phase of uptake was described by an affinity constant of 57±17 μM and a transport capacity of 1867±296 nmol mg membrane protein⁻¹ min⁻¹. At higher zinc levels (>500 μM) a linear, diffusive component of uptake was evident. Zinc transport was also temperature-dependent, with Q₁₀ values suggesting zinc uptake was a carrier-mediated process. Zinc uptake by vesicles in the presence of histidine was correlated to a mono-histidine species (Zn(His)⁺) at all Zn(II) concentrations examined.     

SYNTHETIC AMINO ACIDS AND THE NATURE OF l-DOPA TRANSPORT AT THE BLOOD-BRAIN BARRIER

—The blood-brain barrier transport of amino acids has been measured using the carotid injection technique in the rat. The synthetic amino acids, 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH) and α-(methylamino)isobutyric acid (MeAIB), were model substrates in the Ehrlich cell for the leucine (L) and alanine (A) neutral amino acid transport mechanisms, respectively. The uptake (±)b-[carboxyl-¹⁴C]BCH at the same rate for the five brain regions tested suggested a similarity between regions for the L transport mechanism. At injectant concentrations of 0·1 mm (similar to naturally occurring aromatic neutral amino acids), BCH was mainly taken up by a saturable mediated transport mechanism (K₁, 0·16 mm and V_max, 0·03/μmol/g per min). At higher concentrations, uptake by a nonsaturable or diffusional mechanism could be demonstrated. When BCH was added as a second amino acid to l -[3-¹⁴C]DOPA, the saturable component of l -DOPA transport was significantly inhibited. MeAIB had no measurable effect on the rate of l -DOPA transport. These results suggested that the mediated transport mechanism for l -DOPA at the cerebral capillaries is similar to the l -neutral amino acid transport system.     

Manganese transport by caco-2 cells

The uptake and transport kinetics of manganese (Mn) were investigated in the human intestinal Caco-2 cell line both from the absorption side (apical to basolateral) and from the exsorption side (basolateral to apical). With regard to the former, transport versus time revealed (as uptake) a biphasic pattern with an initial transient phase followed by steady-state conditions. Uptake versus Mn concentrations showed saturation-type kinetics with a 100% increase of Mn binding capacity when measurements were made from 0.5 to 2 h of incubation. The transport characteristics in steady-state conditions exhibited two components, saturable (V_max = 3.70 ± 0.07 nmol/cm²/h, K_m = 32.2 ± 3.4 μM) and nonsaturable (slope = [1.4 ± 0.2] x 10^-6 cm^-2/h) usually presumed to reflect transcellular (carrier mediated) and paracellular (diffusional) pathways, respectively. Mn fluxes were decreased by calcium and calcium antagonists, almost 100% inhibited at 4°C, and affected by quinacrine and ouabain. The inhibition of ATP synthesis was apparently ineffective. From the exsorption side, the Mn fluxes, without a transient period, had an approx 20-fold smaller rate than in the absorptive direction and showed mainly a nonsaturable route (slope = [0.6 ± 0.1] x 10^-6 cm^-2/h). The mechanisms participating in the Mn movements through the monolayer are discussed and proposed to be in common, at least partly, with other divalent cations such as calcium, zinc, or iron.     

Two major pathways of zinc(II) acquisition by human placental syncytiotrophoblast

Uptake of zinc into placental villous syncytiotrophoblast is the first step in its transfer from mother to fetus. To help characterise physiologically significant pathways of zinc accumulation by these cells, we incubated cultured layers of syncytiotrophoblast cells derived from human near-term placental tissue with serum ultrafiltrate (containing the zinc complexed with low molecular mass serum constituents), dialysed serum (containing the zinc bound to the serum proteins) and whole serum, each of whose endogenous zinc was tracer-labelled with ⁶⁵Zn(II). Zinc label from both fractions of serum readily entered a rapidly labelled EDTA-sensitive cellular compartment, probably representing zinc bound to the outside cell surface and in accumulative fashion, an EDTA-resistant compartment, probably consisting largely of internalised cellular zinc. Movement of zinc into the EDTA-resistant pool was strongly temperature-dependent and did not occur via the EDTA-sensitive pool from either serum source. Transfer of zinc from the low molecular mass serum fraction into the EDTA-resistant pool was saturable, the concentration giving half-maximal rate being 1.2 m?mol/l nonprotein-bound zinc. No nonsturable component was detected. Zinc from the serum protein-bound fraction entered by a saturable component, already saturated at physiological total protein-bound zinc concentration, and by an apparently nonsaturable component, not appreciably accounted for by nonspecific fluid-phase endocytosis. The results show that zinc is acquired by placental syncytiotrophoblast from the low molecular mass serum zinc pool probably by a carrier-mediated process, and at least as importantly, from the zinc bound to serum protein, possibly by an endocytic mechanism. © 1995 Wiley-Liss, Inc. © 1995 Wiley-Liss, Inc.     

Ca+2 transport across intestinal brush border membranes of the cichlid teleost Oreochromis mossambicus

Summary Brush border membranes were isolated from tilapia (Oreochromis mossambicus) intestine by the use of magnesium precipitation and differential centrifugation. The membrane preparation was enriched 17-fold in alkaline phosphatase. The membranes were 99% right-side-out oriented as indicated by the unmasking of latent glyceraldehyde-3-phosphate dehydrogenase and acetylcholine esterase activity by detergent treatment. The transport of Ca⁺² in brush border membrane vesicles was analyzed. A saturable and a nonsaturable component in the uptake of Ca⁺² was resolved. The saturable component is characterized by a K _m much lower than the Ca⁺² concentrations predicted to occur in the intestinal lumen. The nonsaturable component displays a Ca⁺² permeability too high to be explained by simple diffusion. We discuss the role of the saturable component as the rate-limiting step in transmembrane Ca⁺² movement, and suggest that the nonsaturable component reflects a transport mechanism operating well below its level of saturation.The authors wish to thank Tom Spanings for his superb organization of fish husbandry, and Maarten de Jong (Dept. of Physiology, Faculty of Medicine, University of Nijmegen) for making the automated stopped-flow apparatus available to us.     

Studies on isolated subcellular components of cat pancreas

Summary Transport of alanine was studied in isolated plasma membrane vesicles from cat pancreas using a rapid filtration technique. The uptake is osmotically sensitive and the kinetics ofl-alanine transport are biphasic showing a saturable and a nonsaturable component. The saturable component is seen only when a sodium gradient directed from the medium to the vesicular space is present. Under this condition an overshooting uptake ofl-but not ofd-alanine occurs. The Na⁺ gradient stimulated uptake ofl-alanine is inhibited byl-serine andl-leucine and stimulated when the membrane vesicles had been preloaded withl-alanine,l-serine orl-leucine.The ionophore monensin inhibits stimulation of uptake caused by a sodium gradient. In the presence of valinomycin or carbonyl cyanidep-trifluoromethoxyphenylhydrazone (CFCCP), the sodium-dependent transport is augmented in vesicles preloaded with K₂SO₄ or H⁺ ions (intravesicular pH 5.5), respectively. In the presence of different anions, the Na⁺-dependent transport is stimulated according to increasing anionic penetration through membranes (lipid solubility). We conclude that a sodium dependent electrogenic amino acid transport system is present in pancreatic plasma membranes.     

Saturable uptake of indol-3yl-acetic Acid by maize roots

The uptake of 5-[³H]indol-3yl-acetic acid (IAA^*) by segments of Zea mays L. roots was measured in the presence of nonradioactive indol-3yl-acetic acid (IAA°) at different concentrations. IAA uptake was found to have a nonsaturable component and a saturable part with (at pH 5.0) an apparent K_m of 0.285 micromolar and apparent V_max 55.0 picomoles per gram fresh mass per minute. These results are consistent with those which might be expected for a saturable carrier capable of regulating IAA levels. High performance liquid chromatography analyses showed that very little metabolism of IAA^* took place during 4 minute uptake experiments. Whereas nonsaturable uptake was similar for all 2 millimeter long segments prepared within the 2 to 10 millimeter region, saturable uptake was greatest for the 2 to 4 millimeter region. High levels of uptake by stelar (as compared with cortical) segments are partly attributable to the saturable carrier, and also to a high level of uptake by nonsaturable processes. The carrier may play an essential role in controlling IAA levels in maize roots, especially the accumulation of IAA in the apical region. The increase in saturable uptake toward the root tip may also contribute to the acropetal polarity of auxin transport.     

Lectin binding to gp60 decreases specific albumin binding and transport in pulmonary artery endothelial monolayers.

The effect of albumin binding to cultured bovine pulmonary artery endothelial cell (BPAEC) monolayers on the transendothelial flux of 125I-labelled bovine serum albumin (BSA) was examined to determine its possible role on albumin transcytosis. The transport of 125I-BSA tracer across BPAEC grown on gelatin- and fibronectin-coated filters (0.8 microns pore diam.) was affected by the presence of unlabelled BSA in the medium in that transendothelial 125I-BSA permeability decreased, reaching a 40% reduction at BSA concentrations equal to or greater than 5 mg/ml. BSA binding to BPAEC monolayers was saturated at concentration of 10 mg/ml with an apparent binding affinity of 6 x 10(-7) M. In contrast, gelatin added to the medium altered neither 125I-BSA binding nor transport. Several lectins were tested for their ability to inhibit 125I-BSA binding and transport. One lectin, Ricinus communis (RCA), reduced 125I-BSA binding by 70% and transport by 40%. Other lectins, Ulex europaeus, Triticum vulgare, and Glycine max decreased neither 125I-BSA binding nor transport. The reduction of 125I-BSA transport by RCA was not observed in the presence of saturating levels of BSA, indicating that RCA influenced only the albumin-dependent component of transport. RCA, but not other lectins, precipitated a 60 kDa plasmalemmal glycoprotein from cell lysates of surface radioiodinated BPAEC monolayers. This 60 kDa glycoprotein appears to be the equivalent of gp60 identified previously as an albumin binding glycoprotein in rat microvascular endothelium. In summary, approximately 40% of albumin transport across BPAEC monolayers is dependent on albumin binding. This component of albumin transport is inhibited by 80% by the binding of RCA to gp60. These results suggest that binding of albumin to gp60 on pulmonary artery endothelial cell membrane is a critical determinant of transendothelial albumin flux involving mechanisms such as plasmalemmal vesicular transcytosis.     

Effect of pH on IAA Uptake by Maize Root Segments

The uptake of [5-³H]indoleacetic acid (IAA) by Zea mays L. root segments involves nonsaturable and saturable processes. The pH optimum of the saturable component was found to be 5.0. The proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone inhibited at 100 micromolar the saturable component of IAA uptake but had no effect on non-saturable uptake. This indicates that the saturable component of IAA uptake is dependent on the proton gradient across the plasmalemma. The high level of proton extrusion in the elongation zone of the root will stimulate nonsaturable and saturable uptake of IAA in that zone.     

The uptake of gibberellin A1 by suspension-cultured Spinacia oleracea cells has a carrier-mediated component

The kinetics of the uptake of [³H]gibberellin A₁ (GA₁) by light- and dark-grown suspension-cultured cells of Spinacia oleracea (spinach) have been studied. Use of nonradioactive GA₁ and gibberellic acid (GA₃) show that the uptake has a saturable and a nonsaturable component. The nonsaturable component increases as the pH is lowered at a fixed concentration of [³H]GA₁ and is probably caused by non-mediated diffusion of the uncharged protonated species of GA₁. The saturable component is not the result of metabolic transformation or to GA₁ binding to the cell wall and is suggested to represent the operation of a transport carrier for which GA₁ and GA₃ are substrates. Auxin, abscisic acid and a cytokinin did not alter the GA₁ uptake. The K_m is approx. 0.3 mol dm^-3 at pH 4.4 in light- and dark-grown cells. The V_max of the carrier is higher in the light-grown cells. The optimum pH for the carrier at a physiological GA₁ concentration (3 nmol dm^-3) was pH 4.0, with no activity detectable at pH 7.0. Both saturable and nonsaturable components were decreased by protonophores indicating that the pH gradient between the cells and the medium may be a component of the driving forces for both types of transport. Both the permeability coefficient for the undissociated GA₁ and the ratio V _max/K _m for the carrier are lower than the corresponding values for the indole-3-acetic acid and abscisic acid carriers studied in other species.Abbreviations and symbols ABA abscisic acid - DMO 5,5-dimethyloxazolidine-2,4-dione - GA gibberellin - GA₃ gibberellic acid - IAA indole-3-acetic acid - P permeability coefficient     

Possible involvement of plasma histidine in differential brain permeability to zinc and cadmium

Zinc gets into the brain parenchyma across the blood-brain and the blood-cerebrospinal fluid barriers, while cadmium hardly gets into the brain parenchyma. Because histidine may be involved in zinc transport across the brain barrier systems, the binding to histidine was compared between zinc and cadmium to understand the difference in brain permeability to both metals. Sephadex G-10 gel filtration indicated that ¹⁰⁹Cd, unlike ⁶⁵Zn, does not bind to histidine. When the plasma incubated with ⁶⁵Zn or ¹⁰⁹Cd was dialyzed in physiological saline containing histidine (0-10 mM), ⁶⁵Zn concentration in the dialysate was increased with the increase of the histidine concentration, suggesting the transfer of zinc from plasma proteins to histidine. The low affinity of zinc to plasma proteins may be important for brain permeability to this metal. On the other hand, ¹⁰⁹Cd was not detected in the dialysate in the presence of 0.1 mM histidine, which is equal to the concentration in the plasma, suggesting no transfer of cadmium from plasma proteins to histidine. These results suggest that the avid binding of cadmium to plasma proteins is related to brain impermeability to this metal.     

BSA‐conjugated zinc oxide nanoparticles as luminescent probes for the determination of histidine

Zinc oxide nanoparticles doped with bovine serum albumin were used to determine histidine in aqueous solutions using a fluorescence spectroscopic technique. The results showed that histidine effectively quenched the fluorescence of the modified ZnO nanoparticles, whereas other amino acids did not significantly affect the light emission, thereby allowing selective and sensitive histidine detection in amino acid mixtures. Under optimal conditions (pH 7.0, 25 °C, 10 min preincubation), the detection limit for histidine was ~ 9.87 × 10^–7 mol/L. The high value of the determined quenching rate constant K_q (3.30 × 10¹³ L/mol/s) was consistent with a static quenching mechanism. Copyright © 2015 John Wiley & Sons, Ltd.     

Na+-independent Lysine Transport in Human Intestinal Caco-2 Cells

The nature of transepithelial and cellular transport of the dibasic amino acid lysine in human intestinal epithelial Caco-2 cells has been characterized. Intracellular accumulation of lysine across both the apical and basolateral membranes consists of a Na⁺-independent, membrane potential-sensitive uptake. Na⁺-independent lysine uptake at the basolateral membrane exceeds that at the apical membrane. Lysine uptake consists of both saturable and nonsaturable components. Na⁺-independent lysine uptake at both membranes is inhibited by lysine, arginine, alanine, histidine, methionine, leucine, cystine, cysteine and homoserine. In contrast, proline and taurine are without inhibitory effects at both membranes. Fractional Na⁺-independent lysine efflux from preloaded epithelial layers is greater at the basolateral membrane and shows trans-stimulation across both epithelial borders by lysine, arginine, alanine, histidine, methionine, and leucine but not proline and taurine. Na⁺-independent lysine influx (10 μm) in the presence of 10 mm homoserine shows further concentration dependent inhibition by lysine. Taken together, these data are consistent with lysine transport being mediated by systems b^o,+, y⁺ and a component of very low affinity (nonsaturable) at both membranes. The relative contribution to lysine uptake at each membrane surface (at 10 μm lysine), normalized to total apical uptake (100%), is apical b^o,+ (47%), y⁺ (27%) and the nonsaturable component (26%), and basal b^o,+ (446%), y⁺ (276%) and the nonsaturable component (20%). Northern analysis shows hybridization of Caco-2 poly(A)⁺RNA with a human rBAT cDNA probe. Received: 3 July 1995/Revised: 6 February 1996     

Absorption of copper and copper–histidine complexes across the apical surface of freshwater rainbow trout intestine

Bioavailability is integral in mediating the delicate balance between nutritive and potentially toxic levels of copper in fish diets. Brush-border membrane vesicles isolated from freshwater rainbow trout intestine were used to characterise apical copper absorption, and to examine the influence of the amino acid histidine on this process. In the absence of histidine, a low affinity, high capacity copper uptake mechanism was described. However, when expressed as a function of ionic copper (Cu²⁺), absorption was linear, rather than saturable, suggesting that the saturable curve was an artifact of copper speciation. Conversely, in the presence of l-histidine (780 μM) saturable uptake was characterised. The uptake capacity discerned (J _max of 354 ± 81 nmol mg protein⁻¹ min⁻¹) in the presence of histidine indicated a significantly reduced capacity for copper transport than that in the absence of histidine. To determine if copper uptake was achievable through putative histidine uptake pathways, copper and histidine were incubated in the presence of tenfold greater concentrations of amino acids proposed to block histidine transporters. Accounting for changes in copper speciation, significant inhibition of uptake by glycine and lysine were noted at copper levels of 699 and 1,028 μM. These results suggest that copper–histidine complexes may be transportable via specific amino acid-transporters in the brush-border membrane.     

Effects of cadmium and copper on zinc transport kinetics by isolated renal proximal cells

Zinc, cadmium, and copper are known to interact in many transport processes, but the mechanism of inhibition is widely debated, being either competitive or noncompetitive according to the experimental model employed. We investigated the mechanisms of inhibition of zinc transport by cadmium and copper using renal proximal cells isolated from rabbit kidney. Initial rates of⁶⁵Zn uptake were assessed after 0.5 min of incubation. The kinetics parameters of zinc uptake obtained at 20°C were a J_max of 208.0±8.4 pmol· min⁻¹·(mg protein)⁻¹, aK _m of 15.0±1.5 μM and an unsaturable constant of 0.259±0.104 (n=8). Cadmium at 15 μM competitively inhibited zinc uptake. In the presence of 50 μM cadmium, or copper at both 15 and 50 μM, there was evidence of noncompetitive inhibition. These data suggest that zinc and cadmium enter renal proximal cells via a common, saturable, carrier-mediated process. The mechanisms of the noncompetitive inhibition observed at higher concentrations of cadmium or with copper require further investigation, but may involve a toxic effect on the cytoskeleton.     

A histidine supplement and regulation of the zinc status in Swiss random mice

The effects of histidine on the zinc status are controversial. In mice, we studied the effects of a moderate histidine supplement on the regulation of the zinc status using subcutaneously administered⁶⁵Zn. In animals fed a zinc-adequate diet, histidine supplement did not cause changes in the zinc status (zinc concentrations,⁶⁵Zn tissue distribution, and tissue specific activities). Neither effects on the regulation of the zinc status (⁶⁵Zn retention, excretion and biological half-life) could be demonstrated. However, the combination of a low zinc diet and moderate histidine supplementation caused changes in the regulation of the zinc status (lower⁶⁵Zn retention, associated with increased fecal excretion and a shorter biological half-life), aggravating the dietary deficiency (lower bone zinc, a shift in the⁶⁵Zn tissue distribution). Reviewing the literature, it seems that only a molar histidine/zinc ration of 2,000 or higher will cause zinc deficiency.     

Derepression of amino Acid-h cotransport in developing soybean embryos

The uptake of the unnatural amino acid α-aminoisobutyric acid (AIB) and glutamine by developing soybean (Glycine max Merr. cv Chippewa 64) embryos was investigated. In freshly excised embryos, the accumulation ratio (cytoplasmic concentration/external concentration) of AIB did not exceed 1.0. After an 18-hour preincubation in nitrogen-free medium the accumulation ratio of AIB exceeded 4.5 at an external AIB concentration of 10 micromolar. This indicates the derepression of an active amino acid uptake mechanism operative at low external amino acid concentration. The presence of sucrose, NH₄NO₃, or glutamine during a 21-hour preincubation prior to measuring glutamine uptake inhibited the enhancement of uptake by 43%, 51%, and 96%, respectively. The time course of the decline in free amino acids and the time course of enhancement of amino acid uptake was not consistent with enhanced uptake resulting from relief of transinhibition, but suggested instead the derepression of synthesis of new carriers. The time course of enhancement of amino acid uptake was paralleled by an increase in glutamine-induced depolarization of the membrane potential. The kinetics of glutamine uptake indicated the presence of a saturable and a nonsaturable component of uptake. The saturable component of uptake is attributed to a mechanism of amino acid-H⁺ cotransport which is derepressed by nitrogen and/or carbon starvation. At physiological concentrations of amino acids, uptake through the saturable system in freshly excised embryos is negligible. Thus, uptake through the nonsaturable system is of primary importance in the nitrogen nutrition of developing soybean embryos.     

The influence of zinc status on the kinetics of zinc uptake into cultured endothelial cells

To better understand cellular zinc homeostasis and characterize the zinc transport process, a mammalian cell culture model was utilized to investigate the influence of zinc status on the kinetics of zinc uptake. Culturing conditions were optimized to induce moderate zinc deficiency and zinc excess while still sustaining the general health of the cells. Cells were grown in (1) control medium of 10% fetal bovine serum (FBS) in minimum essential medium (MEM; 5.0 micromol zinc/L), (2) low zinc medium (10% dialyzed FBS in MEM; 1.5 micromol zinc/L), or (3) zinc back medium (10% dialyzed FBS in MEM with zinc added as ZnCl(2); 5.0 micromol zinc/L). Bovine pulmonary artery endothelial cells (BPAEC), porcine aortic endothelial cells (PAEC), and porcine venous endothelial cells (PVEC) were evaluated as to their responsiveness to our zinc-deficient conditions. Zinc uptake was faster (P < 0.001) in all three cell types when they were grown in low zinc medium compared with controls; the increases were 32% in PAEC, 37% in PVEC, and 66% in BPAEC. Further kinetic analysis with BPAEC demonstrated a 31% increase (P < 0.05) in the maximum rate of zinc uptake (Jmax) grown in low zinc medium compared with controls, but no difference (P > 0.05) between the low zinc group and the control group in the concentration at which uptake was half-maximal (K). Zinc uptake into BPAEC grown in excess zinc conditions was not different (P > 0.05) unless the medium contained greater than 50 micromol zinc/L. In conclusion, BPAEC increased their ability for zinc uptake in response to moderate zinc deficiency, but did not change their kinetics of zinc uptake during moderate zinc excess.     

Effects of histidine on tissue zinc distribution in rats

Histidine has been reported to affect body zinc status by increasing urinary zinc excretion. The effects of experimental histidinemia on distribution of⁶⁵Zn in anesthetized rats were studied. Infusion ofl-histidine at a rate sufficient to raise plasma concentrations to approximately 2mm for 6h starting 48 h after a single intraperitoneal⁶⁵Zn injection did not alter⁶⁵Zn activities in a variety of tissues when compared with anesthetized uninfused animals. However, plasma⁶⁵Zn and erythrocyte⁶⁵Zn were decreased, and liver⁶⁵Zn was increased. If⁶⁵Zn was injected intravenously during histidine infusion, net accumulation of zinc by some tissues was increased, but uptake by others was reduced relative to uninfused animals. In all cases, however, uptake expressed relative to plasma⁶⁵Zn levels was increased when allowance was made for the more rapid fall in plasma⁶⁵Zn during histidine infusion. Similar infusions ofd-histidine produced quantitatively similar effects. Since enzymatic mechanisms and amino acid carriers would be expected to show stereoselectivity, such processes are unlikely to be involved in the zinc distribution changes described. The possibility of zinc transport by a hitherto unidentified carrier is discussed. These experiments confirm that histidinemia can affect zinc status, but any associated changes in urinary zinc excretion do not seem adequate to account for the tissue changes found.