PH REGULATION OF ENDOGENOUS ACID PRODUCTION

拟议的研究旨在调查生理上的 新描述的反馈监管系统的重要性和后果 通过调节内源酸来控制酸碱平衡 制作。研究将在以下情况下在人和大鼠身上进行 内源酸产量增加。酸中毒的影响(NH4Cl和 甲硫氨酸)和碱中毒(NaNCO3)对前臂乳酸产生的影响 在厌氧条件下将在正常志愿者身上进行测试，受试者在 低热量生酮饮食与肾功能衰竭患者的关系 无论是外源性或内源性的酸负荷或滞留酸都会影响 进一步的内源酸生产。酸、碱负荷对细胞生长的影响 低热量生酮饮食受试者的酮酸产生将是 检查以评估脂肪(酮)代谢改变对 蛋白质保护和燃料利用。这将通过以下方式实现 酸碱抑制过程中氮平衡和生热作用的测定 对酮的生成有刺激作用。在慢性插管的大鼠中 酮症与克里斯科饮食，我们将调查时间进程和 急性代谢性酸中毒(盐酸输注)、碱中毒(碳酸氢钠)的可逆性 输液)、慢性代谢性酸中毒(饮食中的CaCl2)、碱中毒(氯化物 耗尽高基础饮食)和急性呼吸性酸碱中毒 酮酸生产。因为内源酸的产生通常发生在 特定能量需求的设置，例如。运动中的乳酸和 饥饿过程中的酮酸，这是一种独立于 需求可能对以下领域的能源利用产生广泛影响 生理或病理状态。

The proposed studies are designed to investigate the physiological importance and consequences of a newly described feedback regulatory system that controls acid-base homeostasis by regulating endogenous acid production. Studies will be performed in man and rats in situations where endogenous acid production is increased. The effect of acidosis (NH4Cl and methionine) and alkalosis (NaNCO3) on lactic acid production in the forearm under anerobic conditions will be tested in normal volunteers, subjects on hypocaloric ketogenic diets and patients with renal failure, to investigate whether exogenous or endogenous acid loads or retained acid can influence further endogenous acid production. The effect of acid and base loads on ketoacid production in subjects on hypocaloric ketogenic diets will be examined to evaluate the consequences of altered fat (ketone) metabolism on protein conservation and fuel utilization. This will be accomplished by measuring nitrogen balance and thermogenesis during acid-base inhibition and stimulation on ketogenesis. In chronically catheterized rats made ketotic with a Crisco diet, we will investigate the time course and reversibility of acute metabolic acidosis (HCl infusion), alkalosis (NaHCO3 infusion), chronic metabolic acidosis (CaCl2 in diet), alkalosis (chloride depleted high base diet) and acute respiratory acidosis and alkalosis on ketoacid production. As endogenous acid generation usually occurs in settings of specific energy need, eg. lactic acid during exercise and ketoacids during starvation, a regulatory mechanism independent of those needs may have widespread implications for energy utilization in physiological or pathological situations.