Functional hepatocyte heterogeneity in glutamate, aspartate and α-ketoglutarate uptake: A histoautoradiographical study

Abstract

[3H]glutamate, [3H]alpha-ketoglutarate or [3H]aspartate was injected in physiological concentrations into antegrade (from portal to hepatic vein) or retrograde (from hepatic to portal vein) perfused rat liver, and the tissue distribution of radioactivity was studied by histoautoradiography. Independent of the direction of perfusion, radioactivity was accumulated in a small perivenous liver parenchymal cell population, which surrounded the terminal hepatic venules as a layer of about two to five cells thick. In contrast, accumulation of radioactivity in periportal hepatocytes was low and sometimes not detectable. This distribution pattern roughly resembled that described for the immunohistochemical distribution of glutamine synthetase in liver. The present histoautoradiographic findings demonstrate a predominant uptake of vascular glutamate, aspartate and ketoglutarate into a small perivenous cell population. They confirm previous label incorporation studies in the metabolically intact liver, demonstrating an almost exclusive uptake of vascular glutamate and alpha-ketoglutarate into perivenous glutamine synthetase containing hepatocytes. In addition, evidence is presented suggesting that perivenous uptake of alpha-ketoglutarate may be one determinant for hepatic glutamine synthesis, at least under the experimental conditions used here.

Pyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient mice

“…1(A)), despite both substances having been reported to be effective treatments in some CTLN2 cases [35,36]. Although Asp is known to be impermeable to the plasma membrane of periportal hepatocytes [37], a specific plasma membrane transporter can import citrate into the liver [38]. Our results suggest that citrate, despite being able to be taken up by the liver and potentially stimulate the TCA cycle, had no effect on the ureogenesis in the Ctrn K/K liver, and therefore any beneficial effect observed from the administration of Asp or citrate can only be through their action on organs other than the liver.…”

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…Within 5-30 s after liver perfusion the radiolabeled compounds appeared within two to five cell layers of acinar zone 3 irrespective of whether perfusion was antegrade or retrograde in direction. These cell layers also seem to be involved in the uptake of dicarboxylates such as malate, succinate, fumarate, and oxaloacetate, which may share the cc-ketoglutarate transporter (Stoll and H~iussinger 1991).…”

High protein diet induces pericentral glutamate dehydrogenase and ornithine aminotransferase to provide sufficient glutamate for pericentral detoxification of ammonia in rat liver lobules

“…We have demonstrated recently that the GS-positive hepatocytes contain higher concentrations of glutamate than more upstream hepatocytes (Geerts et al 1997). In the GS-positive zone, a unique transmembane transport system is localized in hepatocytes that is able to transport both glutamate and aspartate from the circulation (Burger et al 1989;Stoll et al 1991). However, the maximal capacity of this transport system is at least one order of magnitude below the maximal capacity of GS and is inhibited by low blood pH, whereas flux through GS is increased under these conditions (Taylor and Rennie 1987).…”