Oxygen Deficit: The Bio-energetic Pathophysiology

Full text

(1)Contents lists available at ISC. International Journal of Applied Exercise Physiology ISSN: 2322-3537. 2014, 3(1). Journal homepage: www.ijaep.com. Oxygen Deficit: The Bio-energetic Pathophysiology Abhay Kumar Pandey Present address: Tutor, Department of Physiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India. Article history: Received 3 may 2014; accepted 23 august 2014. mechanisms affect the amount of oxygen 1. Introduction delivered to them, and these are under Scarcity of oxygen in humans arises via regulatory control of several functional three modes. The environment may have and metabolic systems. low oxygen to breath. There can be disease in respiratory system causing hindrance to 2. Aerobic energy metabolism and uptake of oxygen from environment and the. Cytochrome. oxidase. the circulatory system may be sluggish to enzyme/system supply to body parts that starve for Oxygen delivered to the cells after oxygen.. Thirdly. the. chemico-cellular taken in from the environment, participates. components of blood which carry oxygen in reactions of aerobic energy production may be lowered or defective. In reference through. cytochrome. oxidase. enzyme. to body cells several limiting sites and catalyzed reactions. These mitochondrial.

(2) International Journal of Applied Exercise Physiology. Vol. 3(1). enzymes therefore are the ultimate part of. and cell dysfunction. This involves series. respiratory system procurement of oxygen.. of successive changes in activity of. These enzymes form energy currency or. different enzyme complexes. Hypoxic. microergic molecules ATP and creatine. dysfunction at cellular level starts at. phosphate using glucose from food and. substrate site involving mitochondrial. oxygen. Deficit in oxygen availability. enzyme complex I (MEC I). This initially. decreases this and causes failure of energy. increases but finally depresses the activity. supply to run biological processes. Such. of. state is called tissue hypoxia or failure of. disorder of electron transfer at the NADH-. bioenergetics. Suppression of function of. Coenzyme. Q. the cytochrome oxidase enzyme system by. conjugated. oxidative. external toxic molecules was demonstrated. Finally, the cytochrome oxidase enzymes. first and later even endogenous factors. themselves are affected. This is verified in. infringing upon their functioning are. functional changes studied in neurons,. revealed. State of oxygen deprivation also. myocardial cells or hepatocytes. The ATP. impairs. content then starts declining in proportion. kinetic. properties. of. these. enzymes.. NADH-oxidase. and. causing. process. of. phosphorylation.. to fall in oxygen tension (PO2) in the cell environment.. 3. Principles underlying biological hypoxia. under. oxygen. severity. The. membrane. of. mitochondria gets disrupted as also of other organelles within cells. There is release of enzymes in cytoplasm, active. deprivation The. site. pathway. of. generation of free radical products and half. availability. of energy dependant functional events of. determine changes in energy metabolism. cells. Degradation of adenine nucleotide to. deprivation. of. and/or oxygen. duration. 61.

(3) International Journal of Applied Exercise Physiology. adenosine,. inosine. and. Vol. 3(1). hypoxanthine. pathway and designated as compensatory. increases and finally the cell dies. Total. phase of bio-energetic hypoxia. Stage II,. inactivation of cytochrome oxidase system. the. however, can occur only in complete. characterized by suppression of electron. absence of oxygen or anoxia.. transporting function at site of cytochrome. non-compensated. stage,. is. Status of respiratory enzymes under. b-c in respiratory chain reactions. The. oxygen deprivation has been examined. terminal stage III or bio-energetic hypoxia. (Pelikan PC et al, 1987), and above pattern. involves inhibition of cytochrome oxidase. is verified in states if ischeamia (decreased. under anoxia. All these stages correlate. blood supply) in various organs (Jennings. with phasic changes in ATP content and. RB et.al, 1976; Mela L et.al, 1976;. energy dependent cellular processes and. Narabayashi H et.al, 1982; Okayasu T. parameters regulating life (Belousova VV. et.al, 1985; Rouslin W et.al, 1980; Vietch. et.al, 1992). Only in the terminal phase,. K. there. et.al,. 1992).. Their. experiments. occur. increased. demonstrated not only decreased activity. permeability,. of. in. degradation of adenine nucleotides. The. hypoxia, but also that inhibition of MEC-I. activation of NAD-dependent oxidation. occurs. other. initially in hypoxic state is peculiar urgent. mitochondrial enzymes (Veitch K et.al,. compensatory event of energy system,. 1992). Three stages of bio-energetic. seen also in exercise and stress.. the. NADH-oxidase. before. oxidation. inactivation. of. lipid. membrane. peroxidation. and. hypoxia can be distinguished. Stage I, relates to inactivation of the NADdependent enhancement. oxidation of. and. succinate. 4. Effect of toxic agents. parallel. Specific toxicants of the cytochrome. oxidation. oxidase enzyme system, e.g. cyanides, 62.

(4) International Journal of Applied Exercise Physiology. Vol. 3(1). azide or carbon monoxide inhibit electron. Capacity to resist state of oxygen. transfer and compromise the capacity of. deficit varies in different individuals.. enzymes to react with oxygen and the. Genotype and phenotype of metabolism,. process is called cyto-toxic, histo-toxic or. maturity of regulatory mechanisms and. chemical. chemicals. capacity to re-adjust toward sustaining. suppress MEC-I and impair electron. viability underlie such differences. Such. transfer at NAD-CoQ site. Such agents. variation. include barbiturates, rotenone, piericidine. development, course and outcome of. and several rotenon-like chemicals that. consequent pathological states (Lukjanova. react with hydrophobic site of MEC-I. LD, 1996).. complex. They inflict changes similar to. The animals with different sensitivity to. stage I hypoxia. Respiratory chain may be. acute hypoxia under normal oxygen. involved at other site by different set of. availability and different organization of. chemicals. energy metabolism exhibit differences in. hypoxia.. like. malonate. succinate-dependent competitive. Many. suppresses. oxidation. inhibition. of. is. important. to. determine. through. higher nervous activity (Livanova LM. succinate. et.al, 1992). There is higher activation. dehydrogenase.. under hypoxic state in high resistance. Zinc ion, Antimycin and other. animals. of. NAD-dependent. oxidation. compounds block the respiratory chain. process in brain (Lukjanova LD, 1996),. near the b-c cytochrome or the MEC-III. which correlates to brain resistance against. complex. Potassium cyanide, azide and. hypoxia. The NADH-oxidase pathway in. carbon. brain. oxidases.. monoxide. inhibit. cytochrome. of. low. resistance. animals. is. expressed more but gets limited earlier in contrast to high resistance animals. Neither 63.

(5) International Journal of Applied Exercise Physiology. Vol. 3(1). the mitochondria content nor kinetics of. inactivation. cytochrome. two. Recent findings however rule-out effect of. categories of animals. However, succinate. pH on energy metabolism under hypoxia. oxidase participates more in cellular. (Chambers DE et.al, 1985). Free radicals. respiration reactions in low resistance. may be another factor contributing to. animals, and this further increases under. ischaemic. hypoxic state. Tissue specific features of a. mitochondria and consequent dysfunction. aerobic. of cellular respiration. In presence of. oxidases. energy. differs. formation. in. determine. of. respiratory. hypoxic. damage. NADH,. cytochrome. low. complexes generate superoxide (O2- and. resistance animals exhibits greater affinity. H2O2). This is increased due to initial. for. to. increase in NAD-oxidase activity under. function longer in hypoxic state, when the. hypoxia. In turn the oxygen free radicals. mitochondria start losing cytochrome-C. cause loss of activity of the MEC. due. complexes. cytochrome-C. to. enzyme. and. disruption. in. continues. of. membrane. (Dudchenko AM et.al, 1996).. MEC-I. and. of. individual resistance to oxygen deficit. The oxidase. the. enzymes.. MEC-III. (Dawson TL et.al,. 1993;. Narabayashi H et.al, 1982; Okayasu T et.al, 1985; Veitch K et.al, 1992). Thus,. 5. Mechanisms. of. hypoxic. electron. transport and. between. NADH-. dysfunction of respiratory chain. dehydrogenase. ubiquinone. is. enzymes. markedly, and between ubiquinone and cytochrome is partially inactivated. H2O2. Hypoxia associated change in intra-. is prominently involved and can be. cellular pH can be considered one of the. produced also be non-respiratory enzymes. triggers for metabolic disorder leading to. bound to mitochondrial membrane. In 64.

(6) International Journal of Applied Exercise Physiology. Vol. 3(1). chemical or toxic hypoxia the free radical. transport (Toleikis A et.al, 1980)). This. mechanisms are very prominent. Energy. further aggravates free radical damage.. deficient states promote formation of. Calcium is key regulator of cell. xanthin oxidase by proteolytic conversion. metabolism and deregulation of calcium. from xanthine dehydrogenase, in recovery. biology has major significance in hypoxic. from exercise. This process also increases. damage. Hypoxia released calcium from. free oxygen radical formation. Various. intracellular. oxidation reactions of monoamine neuro-. production of highly active eicosanoid. chemicals also cause oxygen free radical. products from arachidonic acid, in addition. generation. Such radicals accumulate in. to free radical generation. There is. hypoxic state and alter physic-chemical. alteration. properties of membrane lipids leading to. activities also. Respiration and energy. disturbance in function of membrane. production is disturbed.. proteins,. transport. proteins,. store. of. which. mitochondrial. activates. enzyme. enzymes,. receptor for normal signals including ion channels and the electrical charge. As a result there is adverse impact on water and ionic. balance. in. cells,. swelling. 6. Correction of hypoxic disorder of bioenergetics. of. mitochondria,. impaired. membrane. Aerobic energy metabolism is essential. phospholipid. metabolism,. increased. for running and regulation of cellular. fluidity and permeability of membranes. processes, threatened in hypoxia. Many. that leaks out in late stages cytochrome C. other disease states share this risk. Drugs. and CoQ with failure of MEC-III electron. with donor-acceptor activity like quinones, Vit K get incorporated into respiratory 65.

(7) International Journal of Applied Exercise Physiology. Vol. 3(1). chain. Then electron flow at NADH-CoQ. metabolism with change in activity of. site is shunted and hypoxic disruption of. MEC and restoration of NAD-dependent. electron flow from NADH to cytochrome. oxidation (Lukjanova LD, 1996). Studies. oxidases is repaired. This is basis for use. of energy metabolism under oxygen deficit. of Vit K in treating myopathies with. are. congenital. Many. contemporary medical research to open. quinones share similar activity but are too. prospects for preventing and treating bio-. toxic for clinical use. Agents promoting. energetic. compensatory. comprehended by realizing that ischaemic. MEC-I. deficiency.. ATP. production. like. succinic acid should be useful but succinic. of. paramount. failure.. significance. This. is. in. easily. cardiac states are chief killers today.. acid poorly enters through biological membrane. Organic succinate containing compounds. like. hydroxy-pyridine. Corresponding. Author:. (Present. Address) Abhay Kumar Pandey. derivatives do not suffer such barrier and prove. protective. in. hypoxic. state.. Additionally, agents like mexitol are able. Tutor Department of Physiology, All India Institute of Medical Sciences, Bhopal, (M.P) India. to permeate succinate to serve energy substrate,. rendering. protection. under. E-mail: [email protected] Phone: +91-7607980255. hypoxia. Supplement of cytochrome C and CoQ lost in late stages of hypoxia from the mitochondria can support electron transfer reactions at the b-c cytochrome site. There also occurs adaptation in response to hypoxic stress via rearrangement of energy. Reference Belousova, V.V., Dudchenko, A.M., Lukjanova, L.D. (1992). The correlation of energyconsuming and energysynthesizing reactions in rat hepatocytes in different O2deficient states. Biull Eksp Biol Med, 114:588-590. 66.

(8) International Journal of Applied Exercise Physiology. Chambers, D.E., Parks, D.A., Patterson, G., Roy, R., McCord, J.M., Yoshida, S., Parmley, L.F., Downey, J.M. (1985). Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol, 17:145-152. Dawson,. T.L., Gores, G.J., Nieminen, A.L., Herman, B., Lemasters, J.J. (1993). Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. Am J Physiol, 264:C961- C967.. Dudchenko, A.M., Luk'ianova, L.D. (1996). Effect of adapting to periodic hypoxia on kinetic parameters of respiratory chain enzymes in the rat brain. Biull Eksp Biol Med, 121:252-255. Jennings, R.B., Gannote, C.E. (1976). Mitochondrial structure and function in acute myocardial ischemic injury. Circ Res, 38:I80-I91. Livanova, L.M., Sarkisova, K.Yu., Luk'yanova, L.D., Kolomeitseva, I.A. (1992). Respiration and oxidative phosphorylation of the mitochondria of the brain of rats with various types of behaviour. Neurosci Behav Physiol, 22:519-525. Lukjanova, L.D. (1996). In Adaptation: Biology and medicine. BK Sharma, N Takeda, NK Ganguly et al (ed) Vol 1. New Delhi, ICMR, pp 261-279.. Vol. 3(1). Mela, L., Goodwin, C.W., Viller, L.D. (1976). In vivo control of mitochondrial enzyme concentrations and activity by oxygen. Am J Physiol, 231:1811-1816. Narabayashi, H., Takeshige, K., Minakami, S. (1982). Alteration of innermembrane components and damage to electron-transfer activities of bovine heart sub-mitochondrial particles induced by NADPHdependent lipid peroxidation. Biochem J, 202:97-105. Okayasu, T., Curtis, M.T., Farber, J.L. (1985). Structural alterations of the inner mitochondrial membrane in ischemic liver cell injury. Arch Biochem Biophys, 236:638-645. Pelican, P.C., Niemann, J.T., Xia , G.Z., Jagels, G., Criley, J.M. (1987). Enhancement of mitochondrial oxidative phosphorylation capability by hypoperfusion in isolated perfused rat heart. Circ Res, 61:880-888. Rouslin, W., Millard, R.W. (1980). Canine myocardial ischemia: defect in mitochondrial electron transfer complex I. J Mol Cell Cardiol, 12:639-645. Toleikis, A., Dzeja, P., Praskevicius, A., Jasaitis, A. (1980). Mitochondrial functions in ischemic myocardium. I. Proton electrochemical gradient, inner membrane permeability, calcium transport and oxidative phosphorylation in isolated 67.

(9) International Journal of Applied Exercise Physiology. Vol. 3(1). mitochondria. J Mol Cell Cardiol, 11:57-76. Veitch,. K., Hombroeckx, A., Caucheteux, D., Pouleur, H., Hue, L. (1992). Global ischaemia induces a biphasic response of the mitochondrial respiratory chain. Anoxic pre-perfusion protects against ischaemic damage. Biochem J, 281:709-715.. 68.

(10)

No results found