Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Derangements in Cellular Oxygen Metabolism

  • Chapter
Mechanisms of Organ Dysfunction in Critical Illness

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICMSOFT,volume 38))

  • 104 Accesses

Abstract

As strict aerobic living organisms, mammals, including human beings, are dependent on oxygen for survival. It is, therefore, not possible for them to lack oxygen, except for a very short period, without sustaining severe and irreversible damage or death. Oxygen, however, can be an extremely toxic compound, and, except for erythrocytes, cells lacking mitochondria, cannot be stored in the body. Hence, our complex organism must achieve the very difficult task of supplying energy to the cell via mitochondrial oxidative phosphorylation in such a way that a precise and permanent adjustment to needs is achieved. Moreover, this task must be done almost without the facility to store either oxygen or ATP. Consequently, any modification or derangement to oxygen supply must be tightly linked to cellular adaptations in both the hierarchy and the magnitude of the ATP-dissipating systems. Conversely, any change in cellular energy needs must be immediately accompanied by a suitable modification in oxygen delivery and consumption. Clearly, oxygen supply must be tightly controlled; there must always be enough but never too much. Understanding and treating derangements in cellular oxygen metabolism is therefore complex.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Leverve X (1998) Metabolic and nutritional consequences of chronic hypoxia. Clin Nutr 17:241–251

    Article  PubMed  CAS  Google Scholar 

  2. Schols AM, Fredrix EW, Soeters PB, Westerterp KR, Wouters EF (1991) Resting energy expenditure in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 54:983–987

    PubMed  CAS  Google Scholar 

  3. Hugli O, Schutz Y, Fitting JW (1996) The daily energy expenditure in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 153:294–300

    Article  PubMed  CAS  Google Scholar 

  4. De Duwe CR (1995) Vital Dust. Life as a Cosmic Imperative. Harper Collins Inc., Glasgow

    Google Scholar 

  5. Piquet MA, Fontaine E, Sibille B, Filippi C, Keriel C, Leverve XM (1996) Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes: effect on glycerol metabolism. Biochem J 317:667–674

    PubMed  CAS  Google Scholar 

  6. Rigoulet M, Leverve X, Fontaine E, Ouhabi R, Guerin B (1998) Quantitative analysis of some mechanisms affecting the yield of oxidative phosphorylation: dependence upon both fluxes and forces. Mol Cell Biochem 184:35–52

    Article  PubMed  CAS  Google Scholar 

  7. Denton RM, McCormack JG (1986) The calcium sensitive dehydrogenases of vertebrate mitochondria. Cell Calcium 7:377–386

    Article  PubMed  CAS  Google Scholar 

  8. Saks VA, Khuchua ZA, Vasilyeva EV, Belikova O, Kuznetsov AV (1994) Metabolic compartmentation and substrate channelling in muscle cells. Role of coupled creatine kinases in in vivo regulation of cellular respiration-a synthesis. Mol Cell Biochem 133:155–192

    Article  PubMed  Google Scholar 

  9. Saks VA, Tiivel T, Kay L, et al (1996) On the regulation of cellular energetics in health and disease. Mol Cell Biochem 160-161:195–208

    Article  PubMed  CAS  Google Scholar 

  10. Ventura-Clapier R, Veksler VK, Elizarova GV, Mekhfi H, Levitskaya EL, Saks VA (1987) Contractile properties and creatine kinase activity of myofilaments following ischemia and reperfusion of the rat heart. Biochem Med Metab Biol 38:300–310

    Article  PubMed  CAS  Google Scholar 

  11. Pissarek M, Bigard X, Mateo P, Guezennec CY, Hoerter JA (1997) Adaptation of cardiac myosin and creatine kinase to chronic hypoxia: role of anorexia and hypertension. Am J Physiol 272:H1690–H1695

    PubMed  CAS  Google Scholar 

  12. Gellerich FN, Trumbeckaite S, Opalka JR, et al (2000) Function of the mitochondrial outer membrane as a diffusion barrier in health and diseases. Biochem Soc Trans 28:164–169

    PubMed  CAS  Google Scholar 

  13. Kay L, Daneshrad Z, Saks VA, Rossi A (1997) Alteration in the control of mitochondrial respiration by outer mitochondrial membrane and creatine during heart preservation. Cardiovasc Res 34:547–556

    Article  PubMed  CAS  Google Scholar 

  14. Saks VA, Kapelko VI, Kupriyanov VV, et al (1989) Quantitative evaluation of relationship between cardiac energy metabolism and post-ischemic recovery of contractile function. J Mol Cell Cardiol 21(Suppl l):67–78

    Article  PubMed  Google Scholar 

  15. Beutner G, Ruck A, Riede B, Brdiczka D (1997) Complexes between hexokinase, mitochondrial porin and adenylate translocator in brain: regulation of hexokinase, oxidative phosphorylation and permeability transition pore. Biochem Soc Trans 25:151–157

    PubMed  CAS  Google Scholar 

  16. Brdiczka D, Beutner G, Ruck A, Dolder M, Wallimann T (1998) The molecular structure of mitochondrial contact sites. Their role in regulation of energy metabolism and permeability transition. Biofactors 8:235–242

    Article  PubMed  CAS  Google Scholar 

  17. Steinlechner-Maran R, Eberl T, Kunc M, Schrocksnadel H, Margreiter R, Gnaiger E (1997) Respiratory defect as an early event in preservation-reoxygenation injury of endothelial cells. Transplantation 63:136–142

    Article  PubMed  CAS  Google Scholar 

  18. Kuznetsov AV, Brandacher G, Steurer W, Margreiter R, Gnaiger E (2000) Isolated rat heart mitochondria and whole rat heart as models for mitochondrial cold ischemia-reperfusion injury. Transplant Proc 32:45

    Article  PubMed  CAS  Google Scholar 

  19. Gnaiger E, Rieger G, Stadlmann S, Amberger A, Eberl T, Margreiter R (1999) Mitochondrial defect in endothelial cold ischemia/reperfusion injury. Transplant Proc 31:994–995

    Article  PubMed  CAS  Google Scholar 

  20. Saks V, Dos Santos P, Gellerich FN, Diolez P (1998) Quantitative studies of enzyme-substrate compartmentation, functional coupling and metabolic channelling in muscle cells. Mol Cell Biochem 184:291–307

    Article  PubMed  CAS  Google Scholar 

  21. Leclercq P, Filippi C, Sibille B, Hamant S, Keriel C, Leverve X (1997) Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats. Biochem J 325:519–525

    PubMed  CAS  Google Scholar 

  22. Nobes CD, Hay WW Jr, Brand MD (1990) The mechanism of stimulation of respiration by fatty acids in isolated hepatocytes. J Biol Chem 265:12910–12915

    PubMed  CAS  Google Scholar 

  23. Wojtczak L, Schónfeld P (1993) Effect of fatty acids on energy coupling processes in mitochondria. Biochim Biophys Acta 1183:41–57

    Article  PubMed  CAS  Google Scholar 

  24. Leverve X, Sibille B, Devin A, Piquet MA, Espie P, Rigoulet M (1998) Oxidative phosphorylation in intact hepatocytes: quantitative characterization of the mechanisms of change in efficiency and cellular consequences. Mol Cell Biochem 184:53–65

    Article  PubMed  CAS  Google Scholar 

  25. La Noue K, Schoolwertt A (1979) Metabolite transport in mitochondria. Annu Rev Biochem 48:871–922

    Article  Google Scholar 

  26. Brand M, Chien L, Ainscow E, Rolfe D, Porter R (1994) The causes and functions of mitochondrial proton leak. Biochim Biophys Acta 1187:132–139

    Article  PubMed  CAS  Google Scholar 

  27. Nicholls DG, Locke RM (1984) Thermogenic mechanisms in brown fat. Physiol Rev 64:1–64

    PubMed  CAS  Google Scholar 

  28. Boss O, Muzzin P, Giacobino J-P (1998) The uncoupling proteins, a review. Eur J Endocrinol 139:1–9

    Article  PubMed  CAS  Google Scholar 

  29. Sanchis D, Fleury C, Chomiki N, et al (1998) BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J Biol Chem 273:34611–34615

    Article  PubMed  CAS  Google Scholar 

  30. Brand M, Couture P, else P, Wither K, Hulbert A (1991) Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater than in a reptile. Biochem J 275:81–86

    PubMed  CAS  Google Scholar 

  31. Sibille B, Keriel C, Fontaine E, Catelloni F, Rigoulet M, Leverve XM (1995) Octanoate affects 2, 4-dinitrophenol uncoupling in intact isolated rat hepatocytes. Eur J Biochem 231:498–502

    Article  PubMed  CAS  Google Scholar 

  32. Sibille B, Ronot X, Filippi C, Nogueira V, Keriel C, Leverve X (1998) 2, 4-dinitrophenol-uncoupling effect on DY in living hepatocytes depends on reducing-equivalent supply. Cytometry 32:102–108

    Article  PubMed  CAS  Google Scholar 

  33. Sibille B, Filippi C, Piquet M-A, et al (2001) The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate. Biochem J 355:331–335

    Article  Google Scholar 

  34. Negre-Salvayre A, Hirtz C, Carrera G, et al (1997) A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. Faseb J 11:809–815

    PubMed  CAS  Google Scholar 

  35. Korshunov SS, Korkina OV, Ruuge EK, Skulachev VP, Tarkov AA (1998) Fatty acids as natural uncouplers preventing generation of O2-° and H2O2 by mitochondria. FEBS lett 435: 215–218

    Article  PubMed  CAS  Google Scholar 

  36. Arsenijevic D, Onuma H, Pecqueur C, et al (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26:435–439

    Article  PubMed  CAS  Google Scholar 

  37. Pecqueur C, Alves-Guerra MC, Gelly C, et al (2001) Uncoupling Protein 2: in vivo distribution, induction upon oxidative stress and evidence for translational regulation. J Biol Chem 276:8705–8712

    Article  PubMed  CAS  Google Scholar 

  38. Echtay KS, Winkler E, Klingenberg M (2000) Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature 408:609–613

    Article  PubMed  CAS  Google Scholar 

  39. Ichas F, Mazat JP (1998) From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low-to high-conductance state. Biochim Biophys Acta 1366:33–50

    Article  PubMed  CAS  Google Scholar 

  40. Bernardi P, Petronilli V (1996) The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal. J Bioenerg Biomembr 28:131–138

    Article  PubMed  CAS  Google Scholar 

  41. Kietzmann T, Porwol T, Zierold K, Jungermann K, Acker H (1998) Involvement of a local fenton reaction in the reciprocal modulation by 02 of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene and the insulin-dependent activation of the glucokinase gene in rat hepatocytes. Biochem J 335:425–432

    PubMed  CAS  Google Scholar 

  42. Chandel NS, Schumacker PT (2000) Cellular oxygen sensing by mitochondria: old questions, new insight. J Appl Physiol 88:1880–1889

    Article  PubMed  CAS  Google Scholar 

  43. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95:11715–11720

    Article  PubMed  CAS  Google Scholar 

  44. Bunn HF, Gu J, Huang LE, Park JW, Zhu H (1998) Erythropoietin: a model system for studying oxygen-dependent gene regulation. J Exp Biol 201:1197–1201

    PubMed  CAS  Google Scholar 

  45. Hochachka P, Lutz P, Sick T, Rosenthal M, van den Thillart G (1993) Volume overview: hypoxia defense and adaptational strategies. In: Hochachka P, Lutz P, Sick T, Rosenthal M, van den Thillart G (eds) Surviving Hypoxia. Mechanisms of Control and Adaptation. CRC Press, London, 1–4

    Google Scholar 

  46. Ratcliffe PJ, O’Rourke JF, Maxwell PH, Pugh CW (1998) Oxygen sensing, hypoxia-inducible factor-1 and the regulation of mammalian gene expression. J Exp Biol 201:1153–1162

    PubMed  CAS  Google Scholar 

  47. Kietzmann T, Freimann S, Bratke J, Jungermann K (1996) Regulation of the gluconeogenic phosphoenolpyruvate carboxykinase and glycolytic aldolase A gene expression by 02 in rat hepatocyte cultures. Involvement of hydrogen peroxide as mediator in the response to 02. FEBS Lett 388:228–232

    Article  PubMed  CAS  Google Scholar 

  48. Jungermann K, Kietzmann T (2000) Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology 31:255–260

    Article  PubMed  CAS  Google Scholar 

  49. Kietzmann T, Jungermann K (1997) Modulation by oxygen of zonal gene expression in liver studied in primary rat hepatocyte cultures. Cell Biol Toxicol 13:243–255

    Article  PubMed  CAS  Google Scholar 

  50. Hochachka PW, Buck LT, Doll CJ, Land SC (1996) Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci USA 93:9493–9498

    Article  PubMed  CAS  Google Scholar 

  51. Hotchkiss RS, Karl IE (1992) Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 267:1503–1510

    Article  PubMed  CAS  Google Scholar 

  52. Anning PB, Sair M, Winlove CP, Evans TW (1999) Abnormal tissue oxygenation and cardiovascular changes in endotoxemia. Am J Respir Crit Care Med 159:1710–1715

    Article  PubMed  CAS  Google Scholar 

  53. Fink M (1997) Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl 110:87–95

    Article  PubMed  CAS  Google Scholar 

  54. Fink MP (2000) Cytopathic hypoxia. A concept to explain organ dysfunction in sepsis. Minerva Anestesiol 66:337–342

    PubMed  CAS  Google Scholar 

  55. Hotchkiss RS, Song SK, Neil JJ, et al (1991) Sepsis does not impair tricarboxylic acid cycle in the heart. Am J Physiol 260:C50–C57

    PubMed  CAS  Google Scholar 

  56. Schaefer CF, Biber B (1993) Effects of endotoxemia on the redox level of brain cytochrome a, a3 in rats. Circ Shock 40:1–8

    PubMed  CAS  Google Scholar 

  57. Poderoso JJ, Fernandez S, Carreras MC, et al (1994) Liver oxygen uptake dependence and mitochondrial function in septic rats. Circ Shock 44:175–182

    PubMed  CAS  Google Scholar 

  58. Schaefer CF, Biber B, Lerner MR, Jobsis-VanderVliet FF, Fagraeus L (1991) Rapid reduction of intestinal cytochrome a, a3 during lethal endotoxemia. J Surg Res 51:382–391

    Article  PubMed  CAS  Google Scholar 

  59. Beltran B, Mathur A, Duchen MR, Erusalimsky JD, Moncada S (2000) The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death. Proc Natl Acad Sci USA 97:14602–14607

    Article  PubMed  CAS  Google Scholar 

  60. Simonson SG, Welty-Wolf K, Huang YT, et al (1994) Altered mitochondrial redox responses in gram negative septic shock in primates. Circ Shock 43:34–43

    PubMed  CAS  Google Scholar 

  61. Schulze-Osthoff K, Beyaert R, Vandevoorde V, Haegeman G, Fiers W (1993) Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. Embo J 12:3095–3104

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Fundamental and Applied Bioenergetics, Joseph Fourier University, BP 53X, 38041, Grenoble Cedex, France

    X. M. Leverve

Authors
  1. X. M. Leverve
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Intensive Care Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Timothy W. Evans

  2. Division of Critical Care Medicine, University of Pittsburgh Medical Center, Scaife Hall, Room 606, 3550 Terrace Street, Pittsburgh, PA, 15264, USA

    Mitchell P. Fink

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Leverve, X.M. (2002). Derangements in Cellular Oxygen Metabolism. In: Evans, T.W., Fink, M.P. (eds) Mechanisms of Organ Dysfunction in Critical Illness. Update in Intensive Care and Emergency Medicine, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56107-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56107-8_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-42692-9

  • Online ISBN: 978-3-642-56107-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation