SYNAPTOSOMAL UPTAKE OF ALPHA-KETOGLUTARATE AND GLUTAMINE IN THIOACETAMIDE-INDUCED HEPATIC-ENCEPHALOPATHY IN RATS

The kinetics of uptake of two astroglia-derived glutamate (GLU) precur sors, alpha-ketoglutarate (alpha-KG) and glutamine (GLN) were determin ed in synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide (TAA). TAA treatment i ncreased by 33% Vmax for high affinity, low capacity alpha-KG uptake, without influencing its Km. The increase of the uptake capacity for al pha-KG may represent a response of the GLUergic nerve terminals to the decreased cerebral alpha-KG content, which during HE is associated wi th depressed activity of pyruvate carboxylase, an enzyme that replenis hes alpha-KG in astrocytes. The result is thus consistent with the not ion that HE affects the astroglial control of GLUergic neurotransmissi on. The Km and Vmax for the low affinity, high capacity GLN uptake was not affected by TAA treatment.