1 / 54

Outline O 2 discovery O 2 sensing O 2 utilization Non-shivering Thermogenesis -Brown fat

Oxygen. The capable electron acceptor. Outline O 2 discovery O 2 sensing O 2 utilization Non-shivering Thermogenesis -Brown fat -Amino-acids. Photosystem I. e - tp chain. Light ( 4 photons ). Photosystem II. ATP. Chlorophyll. ADP. O 2 + 4H +. 4e -. e - tp chain.

kail
Download Presentation

Outline O 2 discovery O 2 sensing O 2 utilization Non-shivering Thermogenesis -Brown fat

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Oxygen The capable electron acceptor • Outline • O2 discovery • O2 sensing • O2 utilization • Non-shivering • Thermogenesis • -Brown fat • -Amino-acids

  2. Photosystem I e- tp chain Light (4 photons) Photosystem II ATP Chlorophyll ADP O2 + 4H+ 4e- e- tp chain NADP/NADPH + 1.1 V Light (4 photons) Chlorophyll 2H2O Chlorophyll + e- Chlorophyll Oxygenic Photosynthesis consists of two photosystems, I and II Photosystem II performs only when Photosystem I is present to dispose e-

  3. Protocyanobacterium Protocyanobacterium e e - - Type Type I I H H S S 2 2 Loss of Loss of Type Type II II type type II II S S 2 2 e e - - e e - - Chlorobium Chlorobium Type Type I I e e - - H H S S 2 2 Type Type I I Heliobacillus Heliobacillus S S 2 2 An-oxygenic Photosynthesis Protocyanobacterium Either Photosystem I or Photosystem II Never both. Source of electrons : Molecular Hydrogen or Inorganic molecules such as (S2). An-oxygenic species Heliobacillus Chlorobium Modified from Allen & Martin, Nature 2004

  4. An-oxygenic Photosynthesis Is there anything like Protocyanobacteria today? Oscillatoria limnetica, a true cyanobacterium, turns off its genes for Photosystem II in the presence of H2S and thus reverts from Oxygenic to An-oxygenic Photosynthesis Allen & Martin, Nature, 2007

  5. Discovery of Oxygen 1674 Mayow: Demonstrated that only one part of air was necessary for life. That part was removed both by respiration and by fire ”Nitro ariel spirits” (NAS) NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS NAS H2O

  6. Discovery of Oxygen The Phlogiston Theory All combustible materials contain a ”phlogiston” that escape during burning

  7. Discovery of Oxygen Priestley’s experiment, August, 1774. 2Hg + ”Air” + heat 2HgO 2HgO + intense heat 2Hg+ ”Air” Reported to the Royal Society, March 1775 and demonstrated that a mouse survived better in ”Air” from heated HgO. Called it both ”Dephlogisticated air” and ”Fire Air”.

  8. Discovery of Oxygen Scheele, also a Phlogistonist, did the same experiments already 1773. Sent a letter to Lavoisierin September 1774. No response; the letter was lost. Lavoisier denied having seen the letter. Priestley visited Lavoisier in October, 1774 and discussed his experiment. Lavoisier repeated and confirmed. Lavoisier published and called the air ”eminently breathable air”. He never referred to Priestley or Scheele. Several years later Lavoiser called this ”air” - Oxygen. John W Severinghaus Acta Anaesth Scand, 2002

  9. Discovery of Oxygen What about Scheeles letter ? It was re-discovered by E. Grimaux in 1890 in a collection of papers that belonged to MarieAnne Lavoisier. Grimaux published the text but the original was lost again. Re-re-discovered, however, in 1993, when donated to Archives de l’Académie de Sciences John W Severinghaus Acta Anaesth Scand, 2002

  10. Who should go to Stockholm December 10? From the hands of .... ...His Majesty The King Hence, Scheele and Priestley discovered ”Fire Air” Lavoisier repeated the experiments. Understood the physiological role of ”Fire Air” and later called it Oxygen.

  11. Oxygen Sensing In all oxygen consuming mammalian cells the transcriptionfactor Hypoxia Inducible Factor, HIF, is a key regulator The Discovery of HIF opened up for delineation of molecular mechanisms of oxygen regulated gene expression Gregg Semenza, Cell, 1999

  12. Oxygen Sensing Cellular Hypoxia stabilizes HIF-1 HIF-1 is capable of activating over 70 genes In response to hypoxia which mediates adaptive physiological responses such as Angiogenesis Erythropoieses Glycolysis Gregg Semenza,2006

  13. Oxygen Sensing Acute response to hypoxia occurs in seconds or few minutes and involves pre-excisting proteins. Chronic response to hypoxia occurs in a few minutes or more involves gene expression and synthesis of new proteins Gregg Semenza, Progress in Biophysics and Molecular Biology, 2006

  14. Oxygen Sensing lessons from a 1mm worm and sGC Genes encode for various soluable Guanylyl Cyclases (sGC) which bind oxygen These locomotion patterns varies with the sGC’s. Hence, sGC is an important oxygen sensor Bargmann, 2006

  15. Oxygen Sensing Normoxia Hypoxia HIF-1 HIF-1 Prolyl hydoxylases inhibited Prolyl hydoxylases Fe2+ a-keto gluterate HIF-1 no binding to VHL-protein HIF-1 VHL-protein HIF-1 prolyl hydroxylation Ubiguitination Proteosome degrading HIF-1 stabilized and activates genes HIF-1 inactivated

  16. Oxygen Utilization

  17. Oxygen Utilization Two Aspects Non-Shivering Thermogenesis 1. The Brown Adipose Tissue, BAT 2. Amino Acids, AA, as fuels for heat production

  18. Oxygen Utilization Neonatal patho-physiology Organ development - immaturity Temperature balance-BAT

  19. Oxygen Utilization Norepinephrine during normal delivery 100 80 60 40 30 20 10 5 2 1 0.5 0.2 Norepinephrine (nmol/l) after birth parturition 20 25 30 35 w gestational age 1/2 2 24 h 3 6 9 cm cervix dilatation birth Lagercrantz et al 1994

  20. Oxygen Utilization Isolated brown fat cells respond to norepinephrine with increased O2 consumption: thermogenesis

  21. Oxygen Utilization NE AC ß3 ß3 cAMP PK lipid droplet HSL acyl-CoA FFA proton circuit acyl-carn H+ respiratory chain ß-oxidation CAC acyl-CoA thermogenin ATP mitochondrial membrane cell membrane

  22. Oxygen Utilization NE oxygen electrode brown fat cells

  23. Oxygen Utilization Control cells Control cells 400 400 fmol O O min min cell cell . NE NE 2 min 2 min 0 0

  24. +3% halothane Oxygen Utilization Control

  25. Oxygen Utilization Halothane and other volatile anesthetic agents inhibit oxygen utilization in BAT, reduce heat production and hence thermogenesis. This leads to thermoregulatory problems in newborns during surgery

  26. Oxygen Utilization Where is the effect located ?

  27. Oxygen Utilization NE AC ß3 ß3 cAMP PK lipid droplet HSL acyl-CoA FFA proton circuit acyl-carn H+ respiratory chain ß-oxidation CAC acyl-CoA thermogenin ATP mitochondrial membrane cell membrane

  28. Oxygen Utilization Cold-acclimated hamster as a model for the newborn child

  29. Oxygen Utilization Cold-acclimated hamster as a model for the newborn child

  30. Oxygen Utilization Oxygen Oxygen consumption consumption in in awake awake hamster hamster 10 min 10 min NE NE NE NE 1% O 1% O 2 2 ml O ml O 2 2 10 53 12 49 10 53 12 49 • • min min kg kg 0.75 0.75 910510 910510 Female Female hamster hamster 28 w old, 28 w old, cold cold - - adapted adapted 10 w 10 w bw bw . 0.220 kg . 0.220 kg

  31. Oxygen Utilization B. Halothane D % O2 -2 -1 0 NE NE 10 min 3% 1.5% halothane NE-1 RMR-1 RMR-2 NE-2 RMR-3

  32. Oxygen Utilization Hibernation in Medicine Anti-arrhythmics? Organ protection?

  33. Where is the defibrillator? Oxygen Utilization Hibernation in Medicine Anti-arrhythmics Neonates almost never develop ventricular fibrillation just like hedge-hogs, ground squirrels and other hibernators

  34. Oxygen Utilization Hibernation in Medicine Anti-arrhythmics Several explanatory mechanisms such as different: • pattern of adrenergic innervation • melting points for lipids • enzyme temperature activity curves • handling of intracellular Ca2+ • increased size and nos. of connexin-43 gap junctions

  35. Oxygen Utilization O2 dependent oxidative phosphorylation produces ATPthat is consumed within seconds Hibernation in Medicine Organ protection When O2 drops, oxidative phosphorylation becomes less efficient and free radicals are produced Protection from this is a clinical target with implications on surgical procedures, trauma, organ preservation/transplantation

  36. Oxygen Utilization SCIENCE, 2005 H2S Induces a Suspended Animation-like State In Mice Eric Blackstone, 1,2 Mike Morrison, 2 Mark B. Roth2*

  37. Oxygen Utilization Hibernation in Medicine Organ protection 80 ppm H2S for six hours CO2 production and O2 consumption dropped Core body temperature decreased to 12oC Recovery after six hours Follow-up normal

  38. Oxygen Utilization Hibernation in Medicine Organ protection Roth and Nystul ”showed that hibernation states can be induced on demand on animals that do not naturally hibernate” – using H2S!! Scientific American June 2005

  39. Oxygen Utilization Hibernation in Medicine Organ protection H2S reduces oxidative phosphorylation due to a specific, potent and reversible binding to complex IV (cytocrome c oxidase) preventing oxygen from binding Beauchamp Jr 1984

  40. Oxygen Utilization Hibernation in Medicine Organ protection H2S blocks cells from using O2 and triggers suspended animation in mice

  41. Oxygen Utilization Hibernation in Medicine Organ protection Oscillatoria limnetica, a true cyanobacterium, turns off its genes for Photosystem II in the presence of H2S and thus reverts from Oxygenic to An-oxygenic Photosynthesis Allen & Martin, Nature, 2007

  42. Protocyanobacterium Protocyanobacterium e e - - Type Type I I H H S S 2 2 Loss of Loss of Type Type II II type type II II S S 2 2 e e - - e e - - Chlorobium Chlorobium Type Type I I e e - - H H S S 2 2 Type Type I I Heliobacillus Heliobacillus S S 2 2 An-oxygenic Photosynthesis Either Photosystem I or Photosystem II Never both. Source of electrons : Molecular Hydrogen or Inorganic molecules such as (S2). An-oxygenic species Heliobacillus Chlorobium Modified from Allen & Martin, Nature 2004

  43. Oxygen Utilization Hibernation in Medicine Organ protection With regard to ischemia-reperfusion: The shift into ”suspended animation”, using H2S, is an interesting mechanism that might be clinically useful

  44. Oxygen Utilization Amino acid-induced thermogenesis during anesthesia

  45. Oxygen Utilization AWAKE Adminstration of oral protein or i.v. amino acids in the awake state is accompanied by approximately 20 % rise in energy expenditure and heat production Brundin & Wahren, Metabolism 43, 1994

  46. Oxygen Utilization TETRAPLEGIA The thermic effect of i.v. amino acids is normal or supranormal in the spinal man Aksnäs et al., Clin Physiol 15, 1995

  47. 21 Oxygen Utilization During During Anesthesia Anesthesia Awake Awake V Watts (J/s) O , mL /min 2 4 4 0 0 0 0 acids acids acids Amino Amino Amino 26 26 25 25 50 50 acids acids 84 84 47 47 47 50 50 100 100 acids acids Amino Amino Control Control Control Amino Amino 148 148 148 75 75 150 150 Control Control Control

  48. Oxygen Utilization Is the heat produced in ? - Splanchnic or - Extra Splanchnic Tissue

  49. 70 60 Whole body Splanchnic 50 40 Watts 30 20 10 0 Awake subjects Oxygen Utilization

  50. Amino Amino acid acid - - induced induced thermogenesis thermogenesis in in whole whole body body and and splanchnic splanchnic region region 70 70 60 60 Whole Whole body body 50 50 Splanchnic Splanchnic 40 40 30 30 20 20 10 10 0 0 During During anesthesia anesthesia At At awakening awakening Awake Awake and and surgery surgery subjects subjects Oxygen Utilization

More Related