METABOLIC ADAPTATIONS OF NEONATE TO EXTRAUTERINE LIFE

在分娩的几分钟或几小时内，发育成熟的途径 氧化磷酸化，以及显著的 糖异生是一种重要的新陈代谢调节 足够的新生儿对低血糖的防御。初步研究表明 研究表明，在大鼠和兔子出生后的肝脏中，突然出现了一种 腺嘌呤核苷酸从胞浆流入线粒体。这 与耦合呼吸的最大速率的发展有关， 还有随着丙酮酸羧基酶的激活，限速 出生时糖异生的酶。这些发现表明了一个统一的 解释糖异生的假说，以及适当的三磷酸腺苷比率 合成以支持它，在1-2小时内同步开发，而不需要 新的酶合成：有人提出，一种刺激与 分娩触发腺嘌呤核苷酸流入母体 通过一种新的运输机制调节单向 ATP和ADP在线粒体膜内的运动。作为一名 结果，基质腺嘌呤核苷酸池大小迅速增加。 震级。任何定位在基质中的酶，也是腺嘌呤 核苷酸依赖，因此可能突然变得活跃。受影响的反应 包括氧化磷酸化(依赖于ADP)和 丙酮酸羧基酶(依赖于ATP)，这可能解释了3-4倍 糖异生增加。建议用实验来验证这一点。 进一步的假说，并理解 细胞生化水平。需要调查的具体领域包括： 在出生时识别启动生理信号， 新型三磷酸腺苷、二磷酸腺苷在氦气中的转运机制研究 线粒体.特定基质反应对 ATP+ADP池大小的变化；以及总体关系 离体肝细胞对基质变化的糖异生作用 腺嘌呤核苷酸池大小。有理由怀疑新生儿 与母亲糖尿病、呼吸窘迫或 早产可能是由于出生后腺嘌呤的流入延迟所致。 进入母体(这反过来又会延迟出生后的激活 根据所提出的假说的糖异生；)这一想法也 作为这项提议的一部分，将在动物模型中进行研究。

Within minutes or hours of parturition, the maturation of pathways for oxidative phosphorylation, and the onset of significant rates of gluconeogenesis, are important metabolic adjustments required for an adequate neonatal defense against hypoglycemia. Preliminary studies have shown that, in rat and rabbit liver, right after birth, there is a sudden influx of adenine nucleotides from the cytosol into the mitochondria. This is correlated with the development of maximum rates of coupled respiration, and also with the activation of pyruvate carboxylase, the rate-limiting enzyme for gluconeogenesis at birth. These findings suggest a unifying hypothesis to explain how gluconeogenesis, and an adequate rate of ATP synthesis to support it, develop simultaneously within 1-2 hours without new enzyme synthesis: It is proposed that a stimulus associated with parturition triggers the influx of adenine nucleotides into the matrix compartment via a novel transport mechanism that regulates unidirectional movement of ATP and ADP across the inner mitochondrial membrane. As a result, the matrix adenine nucleotide pool size is rapidly increased in magnitude. Any enzymes localized in the matrix, which are also adenine nucleotide-dependent, may thus become suddenly active. Affected reactions include at least those of oxidative phosphorylation (ADP-dependent) and pyruvate carboxylase (ATP-dependent) and this may account for a 3-4 fold increase in gluconeogenesis. Experiments are proposed to test this hypothesis further and to understand the mechanistic details at the cellular-biochemical level. Specific areas to be investigated include: identification of the initiating physiological signals at birth, characterization of the novel ATP, ADP transport mechanism in he mitochondria; the basis for sensitivity of specific matrix reactions to alterations in the ATP+ADP pool size; and the relationship of over-all gluconeogenic rates in isolated hepatocytes to changes in the matrix adenine nucleotide pool size. There are reasons to suspect that neonatal hypoglycemia associated with maternal diabetes, respiratory distress, or prematurity may be caused by a delay in the postnatal influx of adenines into the matrix (which in turn would delay the acture postnatal activation of gluconeogenesis according to the hypothesis proposed;) this idea also will be investigated in animal models as part of this proposal.