PREFERENTIAL UTILIZATION OF ACETATE BY ASTROCYTES IS ATTRIBUTABLE TO TRANSPORT

Exogenous acetate is preferentially metabolized by astrocytes in the C NS, but the biochemical basis for this selectivity is unknown. We obse rved that rat cortical astrocytes produce (CO2)-C-14 from 0.2 mM [C-14 ]acetate at a rate of 0.43 nmol/min per milligram of protein, 18 times faster than cortical synaptosomes. Subsequent studies examined whethe r this was attributable to cellular differences in the transport or me tabolism of acetate. The activity of acetyl-CoA synthetase, the first enzymatic step in acetate utilization, was greater in synaptosomes tha n in astrocytes (5.0 and 2.9 nmol/min per milligram of protein), indic ating that slower metabolism in synaptosomes cannot be attributed to l ack of enzymatic activity. [C-14]Acetate uptake in astrocytes is rapid and time-dependent and follows saturation kinetics (V-max, 498 nmol/m in per milligram of protein; K-m, 9.3 mM). Uptake is inhibited stereos pecifically by L-lactate as well as by pyruvate, fluoroacetate, propio nate, and alpha-cyano-4-hydroxycinnamate (CHC). Preloading astrocytes with L-lactate or acetate, but not D-lactate, pyruvate, or glyoxylate, transaccelerates [C-14]acetate uptake. Acetate uptake by astrocytes a ppears to be mediated by a carrier with properties similar to that of monocarboxylate transport. In contrast, studies with synaptosomes prov ided no evidence for time-dependent, saturable, transaccelerated, or C HC-inhibitable uptake of [C-14]acetate. The high rate of transport in astrocytes compared with synaptosomes explains the rapid incorporation of [C-14]acetate into brain glutamine over glutamate. These findings provide support for the use of acetate as a marker for glial metabolis m and suggest that extracellular acetate in the brain generated from a cetylcholine and ethanol metabolism is accumulated first by astrocytes .