Doublethink in Enzymology

Dec 27, 2022
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Enzymologists believe and teach that an enzyme accelerates the forward and reverse reaction equally, by precisely the same factor (otherwise the second law of thermodynamics would be violated):

"As is true of any catalyst, enzymes do not alter the equilibrium point of the reaction. This means that the enzyme accelerates the forward and reverse reaction by precisely the same factor." http://www.columbia.edu/itc/chemistry/ARCHIVE/chem-c2407_f99/problems/kinetics1.pdf

At the same time, enzymologists intensively study the so called "catalytic bias" - the property of enzymes to accelerate the forward and reverse reaction UNEQUALLY - and develop technologies for tuning the catalytic bias, with the perspective to obtain unidirectional catalysis (only the forward reaction is accelerated):

"Not all hydrogenases are good catalysts for both H+ reduction and H2 oxidation, with several examples exhibiting a distinct and often dramatic “catalytic bias” exerting a disproportionate rate acceleration in one direction of the reaction relative to the other." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653774/

"Catalytic bias refers to the relative rate preference of a catalyst for either the forward or reverse direction...As one example, recent work on Clostridium pasteurianum [FeFe]-hydrogenases which catalyze reversible hydrogen oxidation have shown that the differential stabilization/destabilization of active site oxidation states through either static or dynamic protein interactions can preferentially promote either the hydrogen oxidation or proton reduction direction of the reaction." https://onlinelibrary.wiley.com/doi/abs/10.1002/9781119951438.eibc2770

"However, many enzymes reversibly convert their substrate and product, and if one is interested in catalysis in only one direction, it may be necessary to prevent the reverse reaction...This is the first demonstration, on a specific example, that slowing a step that is rate limiting only when the enzyme works in one direction is a general mechanism for biasing the enzyme in the other direction." https://hal.science/hal-01977597/document

"Interestingly, although [FeFe]-hydrogenases all possess the same active site H cluster, they display a large range of H2 gas oxidation and proton reduction activities, with some displaying a dramatic catalytic bias, that is, the propensity of a catalyst to effect rate of acceleration in one reaction direction over the other. " https://europepmc.org/article/pmc/pmc8653774

"The protein scaffold around an enzyme’s catalytic core exquisitely controls reactivity, including the direction and rate of chemical processes. Scientists refer to this fine tuning as “catalytic bias”—and how it occurs remains widely debated...A research team from three U.S. Department of Energy (DOE) national laboratories and four universities found that subtle changes to the environment surrounding some enzymes can not only change the rate of a cellular reaction by a staggering six orders of magnitude but also its direction. That reversal—the root of the catalytic bias dilemma—is like speeding in one direction at 10 miles-per-second, then going in the opposite direction at 1,000,000 miles-per-second." https://www.pnnl.gov/news-media/remarkable-rate-return-catalytic-bias

"This has resulted in a deeper understanding of the hydrogenase model system and the ability to directly influence catalytic bias. Thus, the work presented here represents key progress towards developing unidirectional catalysts, and demonstrates the possibility of targeted, rational design and implementation of unidirectional catalysts." https://scholarworks.montana.edu/xmlui/handle/1/14621

"When enzymes are optimized for biotechnological purposes, the goal often is to increase stability or catalytic efficiency. However, many enzymes reversibly convert their substrate and product, and if one is interested in catalysis in only one direction, it may be necessary to prevent the reverse reaction...We evidence a novel strategy for tuning the catalytic bias of an oxidoreductase, which consists in modulating the rate of a step that is limiting only in one direction of the reaction, without modifying the properties of the active site." https://pubs.acs.org/doi/10.1021/ja301802r

George Orwell: "Doublethink means the power of holding two contradictory beliefs in one's mind simultaneously, and accepting both of them."
 
Dec 27, 2022
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"2023 workshop on bidirectional catalysis, from molecular machines to enzymes. 11th & 12th September 2023 – Marseille. In enzymology, there has been much interest in trying to elucidate what makes a particular enzyme faster in one direction (a property sometimes called the “catalytic bias”)." http://frenchbic.cnrs.fr/2022/09/22...catalysis-from-molecular-machines-to-enzymes/

A faster-in-one-direction enzyme disproves the second law of thermodynamics, enzymologists. Any thoughts? No?

George Orwell: "Crimestop means the faculty of stopping short, as though by instinct, at the threshold of any dangerous thought. It includes the power of not grasping analogies, of failing to perceive logical errors, of misunderstanding the simplest arguments if they are inimical to Ingsoc, and of being bored or repelled by any train of thought which is capable of leading in a heretical direction. Crimestop, in short, means protective stupidity."