Rise In AMP Concentration Research Articles

Energy metabolism and glycolysis in the human placenta during ischaemia and in normal labour

Summary Ischaemia of the near-term human placenta following separation from the uterus during caesarean section brought about an immediate and rapid fall in tissue ATP concentration, ATP/ADP ratio and ‘energy charge’, and a rise in AmP concentration. These changes appear to be due to a failure of oxidative phosphorylation, rather than to a general breakdown of the adenine nucleotides. At the same time there was no significant breakdown of placental glycogen and no significant increase in the rate of lactate synthesis. These results show that ischaemia does not lead to an appreciable increase in glycolytic rate in the near-term human placenta, despite appropriate changes in the concentrations of the adenine nucleotide effectors of glycolytic activity. A comparison of placentae delivered by normal labour with those delivered without labour, by caesarean section, suggests that the normal labour processes may bring about a similar marked deterioration of placental energy state; and again, no evidence of an increase of glycolysis during labour was found. The results show that the human placenta does not maintain its cellular energy anaerobically during ischaemia, and indicate that this is due to a lack of glycolytic response to anoxia. We suggest that this lack of glycolytic response prevents an undue accumulation of lactate during hypoxic episodes, including labour, which might otherwise be harmful to the fetus. However, it might place the fetus at risk from placental dysfunction during extended ischaemia or prolonged labour.

Protective effect of glutamic acid on cardiac function and metabolism during cardioplegia and reperfusion.

The effect of glutamic acid added to cardioplegic solution containing 20 mM K+ on the cardiac function and metabolism was studied in isolated working rat hearts. 30-min cardiac arrest resulted in profound fall in creatine phosphate and ATP content, by four- and two-fold, respectively, as well as in four-fold rise in AMP content. Simultaneously, during cardioplegia a decline in tissue glutamate and aspartate content and an increase in tissue ammonia and alanine content were found. After reperfusion, an incomplete restoration of ATP, AMP, and creatine phosphate content were observed; the cardiac output recovered only to 39 percent of the initial value. An addition of glutamic acid to cardioplegic solution was associated with significantly less decline in the content of high-energy phosphates and less prominent rise in AMP content during cardioplegia. It also prevented the decline in tissue aspartate content and caused a lesser ammonia accumulation in myocardial tissue due to the activation of glutamine synthesis. In spite of this the tissue ammonia level remained elevated. Reperfusion with Krebs-Henseleit buffer resulted in the recovery of cardiac output to 75% of the initial value as well as better restoration of high-energy phosphate content. The addition of glutamic acid in the perfusate during reperfusion led to further improvement of ATP and creatine phosphate content. It is suggested that an addition of glutamic acid may have beneficial effect in open heart surgery.

Coupling of cerebral metabolism and blood flow in epileptic seizures, hypoxia and hypoglycaemia.

This study examines the possibility that changes of cerebral extracellular pH (PH e) or adenosine concentration may provide coupling mechanisms of a general nautre, adjusting cerebral blood flow (CBF) to metabolic demands. Although there is considerable indirect evidence that CBF varies inversely with pHe, results obtained during the last few years indicate that large increases in flow may occur in the absence of a fall in pHe. Thus, induction of hypoxia or epileptic seizures leads to maximal increase in CBF before pHe falls or even when there is initial alkalosis due to concomitant hypocapnia. Furthermore, CBF increases in hypoglycaemia and after administration of amphetamine, two conditions unassociated with tissue acidosis. The possibility that adenosine may be a coupling factor was examined in hypoxia and during epileptic seizures in rats. In both conditions a four- to fivefold increase in CBF occurs in spite of the fact that tissue adenosine concentrations remain at or below 1 mumolkg-u. It is concluded that adenosine accumulates first when there is a perturbation of cerebral energy state with a rise in AMP concentration. It seems unlikely that adenosine, formed by breakdown of AMP, acts as a general coupling factor.