Glucose metabolism in aquatic animals

水生动物的葡萄糖代谢研究已有100多年的历史，但仍有一些重要的问题有待解决。1)大西洋鳕鱼气腺的葡萄糖代谢。许多鱼利用充气的鱼囊来保持中性浮力。随着鱼的潜水压力每10米增加1个大气压。这会导致鱼囊压缩，为了保持浮力，必须储存更多的气体。在大多数物种中，鱼囊主要通过聚集在血管网络周围的气腺充满氧气。腺细胞产生H+，导致氧气从血红蛋白中排出。H+和O2在血浆中积累，O2通过扩散进入鱼囊。H+是在厌氧糖酵解产生乳酸的过程中产生的。有许多关于鱼膀胱和气腺功能的生理和生化研究，但还没有在现实生活中发生的压力下进行的研究。本实验将首次解决在生理相关条件下气体沉积和葡萄糖代谢的生物化学。新建造的小室能够产生300个大气压的压力，并在受控温度下流过水，这将使新的实验成为可能。鳕鱼将被利用，因为它们有一个离散的气腺，很容易收获。COD可能在2小时内在50到275米之间移动，也可能发生在超过500米的深度。工作将集中在葡萄糖代谢的第一个关键步骤，即通过葡萄糖转运蛋白1将其转运到细胞内，并通过己糖激酶将葡萄糖磷酸化。该计划的目标将是评估在经历正常压力变化的动物中葡萄糖代谢的重要性和气腺中这一过程的控制。2)是否需要胞外葡萄糖来维持胞内pH？一些种类的鱼(如装甲鱼、白鲟鱼)的心脏能够在细胞外pH降低的情况下保持细胞内的pH值，从而维持收缩。PH防御机制尚不清楚，但可能涉及Na+交换，它要求Na+/K+ATPase(NKA)维持Na+平衡。在哺乳动物的心脏中，NKA主要由糖酵解提供能量。在鱼的心脏中，即使在正常的氧气条件下，胞外葡萄糖也主要(如果不是完全的话)直接产生乳酸，这表明糖酵解与补给细胞膜ATPase一致是必要的。这导致了一种假设，即无氧糖酵解是维持phi所必需的。心脏细胞将从鱼类中分离出来，并暴露在含或不含葡萄糖的低Phe的介质中。将跟踪PHI、氧气消耗、乳酸产生和葡萄糖代谢。该计划将阐明葡萄糖代谢在特定功能中的作用，而不是作为生产ATP的一般燃料来源。这将导致我们如何看待葡萄糖的作用的范式转变。 。

Glucose metabolism has been studied in aquatic animals for over 100 years yet there remain important questions to be resolved. 1) Glucose metabolism in Atlantic cod gas gland. Many fish utilize a gas filled swim bladder to maintain neutral buoyancy. As fish dive pressure increases by 1 atm for every 10 m of depth. This causes the swim bladder to compress and in order to maintain buoyancy increased gas must be deposited. In most species the swim bladder is filled primarily with O2 via a gas gland that clusters around a network of blood vessels. The glandular cells generate H+ that causes O2 to unload from haemoglobin. H+ and O2 accumulate in the plasma and O2 moves by diffusion into the swim bladder. H+ is produced from anaerobic glycolysis with the production of lactic acid. There are many studies on the physiology and biochemistry of swim bladder and gas gland function but none have been conducted at pressures that occur in real life. The present experiments will address for the first time the biochemistry of gas deposition and glucose metabolism under physiologically relevant conditions. Novel experiments will be possible with the use of a newly constructed chamber that is capable of developing pressures of 300 atm with flow through water at controlled temperatures. Cod will be utilized since they have a discrete gas gland that is easy to harvest. Cod may travel between 50 and 275 m in 2 hr and may also occur at depths greater than 500 m. Work will focus on the first critical steps in glucose metabolism, i.e. transport into the cell via glucose transporter 1 and phosphorylation of glucose by hexokinase. The objectives of the program will be to assess the importance of glucose metabolism and control of the process in gas gland in animals undergoing normal pressure changes. 2) Is extracellular glucose required to maintain intracellular pH? Hearts from some species of fish (e.g. Armoured catfish, white sturgeon) are able to maintain intracellular pH at decreased extracellular pH allowing maintenance of contraction. The mechanisms of pH defense are unknown but likely involve Na+ exchange which places demands on Na+/K+ ATPase (NKA) to maintain Na+ balance. In mammalian heart, NKA is fueled primarily by glycolysis. In fish hearts, extracellular glucose is directed primarily if not exclusively to lactate production even under normal O2, suggesting a necessity for glycolysis consistent with fueling membrane ATPases. This leads to the hypothesis that anaerobic glycolysis is necessary to maintain pHi. Heart cells will be isolated from fish and exposed to low pHe with or without glucose in the medium. pHi, oxygen consumption, lactate production, and glucose metabolism will be tracked. This program will articulate roles of glucose metabolism that are specific to particular functions as opposed to being a general fuel source for ATP production. This will result in a paradigm shift with respect to how we think about the role of glucose. .