THE EFFECT OF ALBUMIN ON ASTROCYTE ENERGY-METABOLISM IS NOT BROUGHT ABOUT THROUGH THE CONTROL OF CYTOSOLIC CA2-FATTY ACID SEQUESTRATION( CONCENTRATIONS BUT BY FREE)

Albumin is an important serum protein that under normal circumstances is not present in the brain. However, during development, under hypoxi a, or after breakdown of the blood-brain barrier, albumin is found in the brain, where it is able to regulate energy metabolism. In this wor k the mechanism through which albumin regulates astrocyte metabolism w as investigated. Our results show that albumin strongly increases (mor e than 100%) the flux of glucose and lactate through the pyruvate dehy drogenase-catalyzed reaction in astrocytes from primary culture. Howev er, albumin only slightly stimulated other metabolic pathways, such as the tricarboxylic acid cycle or the pentose phosphate shunt, indicati ng that it exerts its effect specifically on the reaction catalyzed by pyruvate dehydrogenase. Although albumin increased cytosolic Ca2+ con centrations in astrocytes, our results show that the increase in pyruv ate dehydrogenase activity promoted by albumin is not due to the enhan cement of Ca2+ concentrations. Indeed, highly purified albumins failed to increase the Ca2+ concentration but did enhance lactate oxidation. In agreement with this, the effect of albumin on lactate oxidation wa s not abolished after Ca2+ depletion. Instead, the presence of fatty a cids inhibited lactate oxidation and counteracted the effect of albumi n, suggesting that albumin activates pyruvate dehydrogenase by binding free fatty acids and/or their CoA-derivatives. (C) 1999 Wiley-Liss, I nc.