Mahoney J R
University of Minnesota, UMHC, Minneapolis 55455.
Med Hypotheses. 1990 Jan;31(1):21-3. doi: 10.1016/0306-9877(90)90047-i.
Recovery of myocardial ATP levels after a period of ischemia is slow, requiring several days to return to normal. The biochemical limitation for ATP recovery appears to be the availability of the adenine nucleotide (AN) precursor, phosphoribosylpyrophosphate (PRPP), which is produced by the phosphorylation of ribose in the hexosemonophosphate shunt (HMP). In fact, ATP precursors, in particular ribose, have been shown to enhance the rate of postischemic ATP recovery. Infusion of exogenous ribose bypasses the rate-limiting steps in the HMP and speeds up adenine nucleotide (AN) biosynthesis. I propose another method for augmenting the rate of postischemic ATP recovery; increase the flux of substrate through the HMP. This would have the effect of making more PRPP available for AN biosynthesis. Effective physiologically and biologically tolerable means for enhancing HMP activity are presently available. These may be of significant utility in facilitating postischemic myocardial energy recovery.
在一段缺血期后,心肌ATP水平的恢复较为缓慢,需要数天才能恢复正常。ATP恢复的生化限制似乎是腺嘌呤核苷酸(AN)前体磷酸核糖焦磷酸(PRPP)的可用性,PRPP是由磷酸戊糖途径(HMP)中核糖的磷酸化产生的。事实上,ATP前体,特别是核糖,已被证明可提高缺血后ATP的恢复速率。输注外源性核糖绕过了HMP中的限速步骤,并加速了腺嘌呤核苷酸(AN)的生物合成。我提出了另一种提高缺血后ATP恢复速率的方法;增加底物通过HMP的通量。这将使更多的PRPP可用于AN的生物合成。目前已有有效且生理上和生物学上可耐受的增强HMP活性的方法。这些方法在促进缺血后心肌能量恢复方面可能具有重要用途。