Catalytic and regulatory properties of phosphofructokinase (PFK) (EC 2.7.1.11), pyruvate kinase (PK) (EC 2.7.1.40), and creatine kinase (CK) (EC 2.7.3.2) from the heart of the red-eared turtle (Pseudemys scripta elegans) were studied. Particular attention was given to those properties of the enzymes which could help to explain the high glycolytic efficiency in this tissue and so provide insights into the selective forces involved in the evolutionary development of an extreme tolerance to anoxia.
The control of glycolytic flux in turtle ventrical muscle has been vested primarily in phosphofructokinase and pyruvate kinase. Creatine phosphate and fructose diphosphate play pivotal roles in the channelling of carbon through the pathway and in the production of metabolic energy as ATP. The levels of these key metabolites are in turn tightly regulated. One of the enzymes studied (phosphofructokinase) controls the levels of fructose diphosphate produced and creatine kinase (itself modulated by the cell's redox balance) controls creatine phosphate levels.
When oxygen levels are reduced, NADH accumulates because of a decrease in electron transport chain regeneration of NAD (129). This leads to an
effective activation of creatine kinase by lowering the Kм for creatine
phosphate. This activation causes a drop in creatine phosphate levels without the decline in ATP levels that are seen at the onset of hypoxia in other tissues ( 4 ). Since the high levels of creatine phosphate present in aerobic heart are responsible for the inhibition of phosphofructokinase by greatly increasing the for its substrate, fructose-6-phosphate, this drop in concentration deinhibits the enzyme and leads to a flush of its product, fructose diphosphate. The increase in fructose diphosphate (1) serves to activate phosphorructokinase by itself, and (2) further reduces the effect of creatine phosphate by a deinhibition of the enzyme. These two effects cause an autocatalytic increase in flux through this locus* Fructose diphosphate also feed-forward activates pyruvate kinase by decreasing the Km for its substrate, phosphoenolpyruvate, and serves to deinhibit this enzyme which is normally inactive due to alanine and ATP inhibition.
The most important feature of such a regulatory system is that it is a kind of autocatalytic cascade. Once the activation of creatine kinase is initiated by the redox imbalance inherent in anaerobiosis, all the various regulatory interactions potentiate one another. Drops in inhibitor levels lead to increases in activator levels and these activators serve to further deinhibit. These interacting effects serve to potentiate anoxic production of energy to compensate for the temporary depletion of oxygen in diving stress and in long periods of hibernation in this turtle, Nature's premier vertebrate anaerobe. / Science, Faculty of / Zoology, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/19161 |
| Date | January 1974 |
| Creators | Storey, Kenneth Bruce |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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