Compartmentation of glucose and fructose 1,6-bisphosphate metabolism in vascular smooth muscle.
Compartmentation of glucose and fructose 1,6-bisphosphate metabolism in vascular smooth muscle.
复制标题
血管平滑肌中葡萄糖和果糖 1,6-二磷酸代谢的区室化。
DOI：
10.1021/bi00004a027
复制
发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Roberts,TM
中科院分区：
文献类型：
--
作者：
Hardin,CD;Roberts,TM
1994年11月18日收到的修订版Mandarin pt ®摘要：我们检查了外源性添加的13 C标记的果糖1，6-二磷酸（标记在第一个和第六个碳或仅标记在第一个碳）和[2- 13 C]葡萄糖在氧合良好和灌流良好的猪颈动脉段中的代谢。外源添加的果糖1，6-二磷酸被猪颈动脉利用并主要参与血管生成，而[3- 13 C]乳酸的产生与零无显著差异。当单独利用[1，6- 13 C]果糖1，6-二磷酸或[1，6 - 13 C]果糖1，6-二磷酸时，在没有通过醛缩酶和磷酸丙糖异构酶代谢的情况下发生产热通量，从而分别形成[1，6- 13 C]-葡萄糖和[1，6 - 13 C]葡萄糖。当[2- 13 C]葡萄糖是唯一的外源底物时，它被利用并专门参与糖酵解通量，产生[3- 13 C]乳酸，而没有从丙糖到[5- 13 C]葡萄糖的产酸通量。当葡萄糖和1，6-二磷酸果糖作为外源底物一起提供时，葡萄糖仍然仅参与糖酵解通量，而没有丙糖参与糖异生，而1，6-二磷酸果糖参与糖酵解通量，其中[3- 13 C]乳酸的产生大约是来自[1，6 - 13 C]果糖的[1，6 - 13 C]葡萄糖产生的大约一半。6-二磷酸。在葡萄糖存在下，[1 - 13 C]果糖1，6-二磷酸也同时参与糖酵解和产酶过程。然而，在[2- 13 C]葡萄糖的存在下，[1 - 13 C]果糖1，6-二磷酸在异源生成之前通过丙糖进行异构化，因为产生了[6- 13 C]葡萄糖。因此，葡萄糖利用的中间体和催化乳酸的中间体似乎不与外源性果糖1，6-二磷酸代谢的中间体混合。糖酵解在血管平滑肌中已被广泛研究，因为这种组织的特征是在良好的氧合条件下高速率的乳酸产生（Paul，1980;哈丁& Paul，1995）。猪颈动脉是一种紧张性血管平滑肌，被认为是研究区室代谢的模型系统。Paul和他的同事已经表明，氧消耗和乳酸产生可以变化，通常是相反的方向（Paul，1983），并提出氧化代谢可以提供ATP特异性用于收缩，而膜相关糖酵解途径可以提供ATP给膜相关ATP酶，如钠泵（坎贝尔和Paul，1992）或钙泵（哈丁等人，1992年）。此外，有相当多的证据表明，葡萄糖分解和糖原分解的途径可能在空间和功能上是分开的。Lynch和Paul（1983）使用均匀标记的[14 C]葡萄糖证明，尽管未标记的糖原被分解，但产生的乳酸盐的比活性与外源施加的葡萄糖的比活性相等。此外，在猪颈动脉中发现了至少两个独立的葡萄糖6-磷酸池（Lynch & Paul，1986）。
Revised Manuscript Received November 18, 1994® abstract: We examined the metabolism of exogenously added 13C-labeled fructose 1, 6-bisphosphate (either labeled at the first and sixth carbons or labeled at the first carbon only) and of [2-13C] glucose in well-oxygenated and well-superfused hog carotid arterysegments. Exogenously added fructose 1, 6-bisphosphate was utilized by hog carotid artery and primarily participatedin gluconeogenesis while the production of [3-13C] lactate was not significantly different from zero. When [l, 6-13C] fructose 1, 6-bisphosphate or [l-13C] fructose 1, 6-bisphosphate was utilized individually, gluconeogenic flux occurred without metabolism through aldolase and triosephosphate isomerase resulting in formation of [1, 6-13C]-glucose and [l-13C] glucose respectively. When [2-13C] glucose was the sole exogenous substrate, it was utilized and exclusively participated in glycolytic flux with production of [3-13C] lactate and no gluconeogenic flux from the trioses to [5-13C] glucose. When both glucose and fructose 1, 6-bisphosphate were provided together as exogenous substrates, glucose still participated exclusively in glycolyticflux with no trioses participatingin gluconeogenesis while fructose 1, 6-bisphosphate participated in glycolytic flux with [3-13C] lactate production approximately being approximately half of the [l, 6-13C] glucose production from [l, 6-13C] fructose 1, 6-bisphosphate. In the presence of glucose,[l-13C] fructose 1, 6-bisphosphate also participated in glycolytic flux and gluconeogenic flux simultaneously. However in the presence of [2-13C] glucose,[l-13C] fructose 1, 6-bisphosphate underwent isomerization through the trioses prior to gluconeogenesis since [6-13C] glucose was produced. Therefore, the intermediates of glucose utilization and catabolism to lactate do not appear to mix with the intermediates of exogenous fructose 1, 6-bisphosphate metabolism. Thus we observed a simultaneous yet separable flux of glycolysis and gluconeogenesis indicating a structural organization of carbohydrate metabolism in vascular smooth muscle.Glycolysis has been extensively studied in vascular smooth muscle since this tissue is characterized by a high rate of lactate production under well-oxygenated conditions (Paul, 1980; Hardin & Paul, 1995). Hogcarotid artery, a tonic vascular smooth muscle, has been considered by many to be a model system for the study of compartmented metabolism. Paul and his colleagues have shown that oxygen con-sumption and lactate production can vary, often in opposite directions (Paul, 1983), and have suggested thatoxidative metabolism may provide ATP specificallyfor contraction while a membrane-associated glycolytic pathway may provide ATP to membrane-associated ATPases such as the sodium pump (Campbell & Paul, 1992) or the calcium pump (Hardin et al., 1992). In addition, there has been considerable evidence that the pathways for glucose breakdown and for glycogen breakdown may be spatially and functionally separate. Using uniformly labeled [14C] glucose, Lynch and Paul (1983) demonstrated that the specific activity of the lactate produced was equal to that of the glucose exogenously applied despite breakdown of unlabeled glycogen. In addition, at least two separate pools of glucose 6-phosphate were found in hog carotid artery (Lynch & Paul, 1986).