Thursday, 2 October 2014

Oxygen - deadly poison

Couple of threads got tangled last night. It turns out that today is Christian de Duve's birthday. He was born in then same month as my Old Man in 1917 and died only last year with a string of fundamental discoveries to his name and a Nobel Prize to polish.  He got the Prize for his discovery and characterisation of lysosomes and peroxisomes: two sub-cellular organelles which have particular and peculiar functions to perform in the metabolism of all eukaryotic cells including our own.  I talk about them in my human physiology course and The Institute in sufficient detail that I have set an exam question on them.  He discovered lysosomes after noticing an intriguing anomaly: the amount of the enzyme he was researching differed according to whether he ground his cell samples in a pestle & mortar or a blender.  Obituaries in the UK Independent and Telegraph contain laughable errors in their description of the science but between the two of them you can work out the source of de Duve's eureka moment.

de Duve and my mentor Lynn Margulis believed that peroxisomes were once free-living microbes that were particularly adept at dealing with the enormous amounts of free gaseous oxygen that was being generated a billion years ago by a new class of microbe that made a living by photosynthesis. They could use the sun's energy to carry out this reaction:
6CO2 + 6H2O --> C6H12O6 + 6O2
This is rather nifty.  Converting a lot of carbon-dioxide and water into sugar from which complex carbohydrates might be built is clearly a useful trick even if it requires energy.  If you can evolve a set of structures and enzymes that can capture this energy from sunlight, then it's a bit of a coup.  If we could do more of it today, that would suck up the most significant green-house gas carbon-dioxide and use it to make sugar, starch, cellulose, wood, coal . . . you get my drift: energy reserves built up and global warming set back for a while. Oxygen is a bio-product from this reaction and that sounds like a bonus. But you have to appreciate that O2 oxygen is so potently reactive that it is toxic to a lot of free-living microbes even today - the germs that cause tetanus Clostridium tetani and gangrene Clostridium perfringens and other bacteria that skulk in dark places a long way from fresh air. The atmosphere is now, and has been steady at for a long long time, just under 20% oxygen and this is evidence for James Lovelock's Gaia - if the concentration was a few percent higher things would spontaneously combust.

de Duve and Margulis noted that peroxisomes are full of enzymes which process and detoxify free oxygen and they independently came to believe that, like mitochondria, these little bodies had once been independent bacteria. The trouble with this hypothesis, which has the ring of truth, is that no trace of any DNA remains which is physically associated with the peroxisome itself.  At least vertebrate mitochondria have retained 16,000 bp of DNA (maybe 1%) from which it can be inferred that they are descended from alpha-proteobacteria like Rickettsia prowazekii. The rest of the original genome has been exported piecemeal and absorbed by the chromosomes of the hosting organism from which we are all [plants, animals, fungi] descended. de Duve reckoned that this process of export had been carried through to completion by the peroxisome, and I'm not going to say any different.

Mais revenons nous a nos Belgiques.  de Duve died in May last year at the time of his choosing.  His wife had passed on five years earlier, he had cancer and heart problems, he was 95 and had recently been injured in a fall, it was time to go. Belgium has the most forward-looking and liberal laws regarding end of life issues and de Duve died with a quiet word and a smile surrounded by his grown up children and assisted by two doctors and a syringe. A lesson to us all.

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