Thursday, May 11, 2023

Transformer

I took lots of notes while reading Transformer, Nick Lane’s latest book. I’ve enjoyed his engaging prose since I stumbled on Oxygen many years ago. Back then, I wasn’t all that interested in biochemistry. Now, I’m fascinated by the subject. The subtitle of Transformer is “The Deep Chemistry of Life and Death”. Sounds like a tall order to explain such a topic.

 


Lane focuses on the Krebs cycle, familiar to students of biochemistry or introductory biology. But he spends quite a bit of time discussing how and when the cycle might run in reverse. This aligns very closely to my own thinking and research in the chemistry of the origin of life, so Lane is preaching to the converted in my case. Many of the chemical details were familiar to me, but I still enjoyed his presentation couched in history and a discussion of the scientists involved.

 

Things that jumped out at me:

·      The role of Rubisco: I did not know about its role as a “safety valve” in photorespiration to resupply NADP+ for ferredoxin. I’d always wondered why nature would keep such an inefficient enzyme, but Lane’s explanation made sense.

·      While the reverse Krebs cycle is autocatalytic (which is important if it plays a role in the chemical origins of life), the forward Krebs cycle is not; in the oxidative direction it is catalytic, but not autocatalytic. I hadn’t previously considered this difference.

·      Lane puts Orgel’s criticisms about “Metabolism First” in context and threads the needle to compromise between ideal autocatalysis and too many parasites bleeding off intermediates from the cycle.

·      The conditions under which dehydration might be favorable in a “watery” environment.

·      The pH challenge: CO2 activity is favored by acidic conditions, while H2 activity is favored by alkaline conditions. Membranes come to the rescue to take advantage of a pH gradient.

·      Biochemical metabolic efficiency for aerobes versus anaerobes connects to the rule-of-thumb of 5 versus 2 trophic levels.

·      Planet Earth is like a “giant battery”, negative (reduced minerals) inside, positive (oxidized atmosphere) on the surface. Volcanoes and hydrothermal vents connect the two! Cells might be analogous with membrane proton pumps as the connection.

·      It’s difficult to use the proton gradient to both reduce ferredoxin and generate ATP simultaneously.

·      The Krebs cycle has two prongs with succinate as the tipping point. Gotta balance growth, reproduction, and staying alive!

·      Mitochondria are flux capacitors.

 

A later chapter on cancer was tougher-going for me because I was not as familiar with the biology and biochemistry. I was reminded how challenging it can be to learn something new where I lacked the specialized vocabulary. But I’m motivated to learn more about control systems in biochemistry so I expect to re-read parts of Lane’s book with a biochemistry textbook open and with some help from the World Wide Web. What I most appreciated about reading Lane’s book was that it made me stop and think about my research projects from a bird’s-eye view, and it gave me some new ideas to explore. It’s good timing because I’m getting excited once again about my research as my semester is coming to a close and my teaching responsibilities ebb.

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