Lecture 5_Hemoglobin_New.pdf

Lecture 5_Hemoglobin_New.pdf - Living with Oxygen the...

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Living with Oxygen, the Hemoglobin and Myoglobin Story – Molecules to Breath With A case study on protein structure function and binding Learning outcomes By the end of the lecture, a successful student will be able to: - Describe a general overview of the various methods of transporting and storing oxygen in biological systems - Describe the structure of the three proteins responsible for transporting and storing dioxygen (hemoglobin, hemocyanin, hemerythrin) as well as the storage protein myoglobin, with hemoglobin in more detail. - Describe how each of the above binds to dioxygen - Understand how binding of dioxygen can affect the structure of hemoglobin, and the subsequent effects (co operative and allosteric binding, Bohr effect, etc.) - Appreciate the key importance and the risks associated with the chemistry of oxygen
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DNA ‘Information store’ – chemically encoded - Genes RNA ‘short term information transfer’ TRANSCRIPTION ‘Proteins’ – Tools that cells use to do what needs to be done ‘Enzymes or biological catalysts’ Revision I - Molecules of Life and the Central Dogma of Molecular Biology
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Proteins are made from 20 basic building blocks called amino acids (10 -3 M) Na > K > Mg > Ca > Fe > Zn > Cu > Mn > Mo > Co > Se (10 -15 M) Those involved in oxygen activation Fe > Cu > (Zn) > Mn > Mo (Cu/Zn) Menkes disease, Wilsons disease, Alzheimers, ALS, CJD Some 19 metal ions are essential for life Revision II
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3.5-2.5 billion Methane, ammonia, carbon dioxide, and water Cyanobacteria Sharks Bay - Stromatolites on the shores of WA Highly Reducing -340mV Highly Oxidising + 800mV 2.5-0.5 billion <0.1% oxygen 1 st great oxygenation event 2.2 billion ~3% oxygen 1 billion red/green algae 250-65 million 0.5-0.25 billion First higher plants Modern animals and plants Eukaryotes 2 nd great oxygenation event – 1.0 billion Oxygen and the Timelines for Life on Planet Earth! H2S, carbon dioxide, and Sulphuric acid
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Early water splitting enzymes - based on photo system II. • 2.2 billion, more advanced photosynthesis incorporating a water splitting reaction. • The first great oxygenation event ~3% oxygen - mass bacterial extinction. • Oxidative respiration /early eukaryotes • Nitrogen cycle starts. • Second great oxygenation even 1.0 billion
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Oxygen Reduction is Playing with Fire! Fe 2 + + H 2 O 2 ® Fe 3 + + OH + OH - Fe 2+ + O 2 « Fe 2 + -O 2 « Fe 3 + -O 2 « Fe 3 + + O 2 •- O 2 •- + H + « HO 2 2HO 2 « H 2 O 2 + O 2 2O 2 + 2H + « H 2 O 2 + O 2
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O 2 + 4H + + 4e - ® 2H 2 O (terminal oxidase) RH + 2H + + 2e - + O 2 ® R-OH + H 2 O (monoxygenases, P450’s) 2H 2 O 2 ® 2H 2 O + 0 2 (catalases) 2RH + H 2 O 2 ® 2R + 2H 2 O (peroxidases) RH + H 2 O 2 ® R-OH + H 2 O (peroxygenases) Hemprotein catalysed reactions Living with Oxygen is Dangerous - but there is not much choice!
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Transporting and storing O 2 without destroying it - Transport: - only required when the size of organism puts limit on O 2 distribution - Dioxygen has a number of different functions in biological systems - terminal acceptor in respiratory chain - oxygenation of organic molecules - Storage - required when O 2 supply might be stopped (for instance, whales)
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