Thursday, April 27, 2006

Evolving enzymes

Evolving enzymes: A catalyst uses quantum mechanics to speed chemical reactions, The Economist, April 15th 2006 ...

[Graphic: Wikipedia, "Enzyme"]

IMAGINE hitting a tennis ball against a wall. Time after time, the ball bounces back. But, just occasionally, the ball disappears only to reappear on the other side of the wall. The wall is solid; no bricks are missing. It sounds surreal, but in the weird world of quantum mechanics such occurrences, involving very small objects over very short distances, are an everyday effect known as quantum tunnelling. [Also at Seed Magazine. This could be a very important (perhaps even Nobel prize-winning) discovery, if it turns out to be true.]

Whether such an effect could account for odd behaviour at larger sizes and distances has long been the subject of debate. In particular, it is of interest to chemists, who want to know how a group of proteins called enzymes speedup, or catalyse, chemical reactions at rates that are, in some cases, millions of times faster than the reaction rate in their absence. This is important because, in the absence of enzymes, most chemical reactions in biological cells would occur too slowly to support life. [If it turns out that some enzymes exploit quantum tunnelling, then that would be yet another fine-tuned for life parameter of the Universe.]

The answer, reported in this week's issue of Science, is that enzymes also exploit this quantum-mechanical loophole. Like all catalysts, enzymes work by providing a chemical reaction with an alternative pathway that has a lower energy threshold to get it going. Nature will take the path of least resistance, just as a ball left to roll about in a bowl will settle inert at the bottom of the vessel. The question is: exactly how does the enzyme change the energy barrier for the chemical transformation such that the ball tunnels through the side of the bowl rather than languishing at its bottom? The researchers, based at the University of Manchester and the University of Bristol, both in Britain, studied a compound called tryptamine, which belongs to a group of neurotransmitters and other chemical messengers that contain a nitrogen and two hydrogen atoms connected to an "aromatic" ring by a two-carbon chain. By common convention, an enzyme's name describes what it does, followed by the ending "ase". So an enzyme called aromatic amine dehydrogenase (AADH) removes hydrogen from tryptamine. [It is going to be really interesting if neurotransmission requires quantum tunnelling!

That might then support Roger Penrose's theory that intelligence is not substrate-neutral (as artificial intelligence maintains), but the mind (even of lowly organisms) derives its power from the cellular ultrastructure of neurons:

"Yet there must indeed be a complicated control system governing the behaviour of a paramecium-or indeed other one-celled animals like amoebas- but it is not a nervous system. The structure responsible is apparently part of what is referred to as the cytoskeleton. As its name suggests, the cytoskeleton provides the framework that holds the cell in shape, but it does much more. It is the cytoskeleton's role as the cell's 'nervous system' that will have the main importance for us here. For our own neurons are themselves single cells, and each neuron has its own cytoskeleton! Does this mean that there is a sense in which each individual neuron might itself have something akin to its own 'personal nervous system'? This is an intriguing issue, and a number of scientists have been coming round to the view that something of this general nature might actually be true. ... In order to address such issues, we should first glimpse the basic organization of the cytoskeleton. It consists of protein-like molecules arranged in various types of structure: actin, microtubules, and intermediate filaments. ... The 'control centre' of the cytoskeleton ... is a structure known as the centriole. This seems to consists essentially of two cylinders of nine triplets of microtubules ... The centriole forms the critical part of a structure called the microtubules organizing centre or centrosome. ... the centriole, which seems to be the focal point of the cytoskeleton, a structure that apparently controls the cell's movements and its detailed organization. ... Hameroff and his colleagues have argued, for more than a decade, that microtubules may play roles as cellular automata, where complicated signals could be transmitted and processed along the tubes as waves of differing electric polarization states of the tubulins. Recall that tubulin dimers can exist in (at least) two different conformational states that can switch from one to the other, apparently because of alternative possibilities for their electric polarizations. ... Indeed, if tubulin dimers are the basic computational units, then we must envisage the possibility of a potential computing power in the brain that vastly exceeds that which has been contemplated in the AI literature. Hans Moravec, in his book Mind Children (1988), assumed, on the basis of a 'neuron alone' model, that the human brain might in principle conceivably achieve some 1014 basic operations per second, but no more, where we consider that there might be some 1011 operational neurons, each capable of sending about 103 signals per second . If, on the other hand, we consider the tubulin dimer as the basic computational unit, then we must bear in mind that there are some 107 dimers per neuron, the elementary operations now being performed some 106 times faster, giving us a total of around 1027 operations per second. Whereas present-day computers may be beginning to close in on the first figure of 1014 operations per second, as Moravec and others would strongly argue, there is no prospect of the 1027 figure being achieved in the foreseeable future. ... it is clear that the possibility of 'microtubular computing' (cf. Hameroff 1987) puts a completely different perspective on some of the arguments for imminent human-level artificial intelligence." (Penrose, R., "Shadows of the Mind: A Search for the Missing Science of Consciousness," [1994], Vintage: London, 1995, reprint, p.357-366)]

Hydrogen, the simplest atom, consists of a single proton encircled by a single electron. As electrons are point-like, their quantum mechanical behaviour is well known. But protons are far bigger, and the idea that they might be able to quantum tunnel is more controversial. Yet the AADH catalyses the breakage of the otherwise very stable, carbon-hydrogen bond at ambient temperatures, a feat that would appear to be impossible. Something strange must be going on. The researchers suspect that protons as well as electrons are undergoing quantum tunnelling, that is, hydrogen itself is quantum tunnelling. [The proton has about 1836 times more mass than an electron, so that presumably makes it difficult to see how it could be involved in quantum tunnelling. But maybe part of it (a proton is composed of three quarks) can be?]

The team used x-ray crystallography experiments combined with computational simulations to examine the chemical reactions involved. The researchers caught an intermediate step in the process by which hydrogen is removed from tryptamine, namely the point at which a proton disappears from a carbon atom as the carbon-hydrogen bond breaks. They argue that this happens because the enzymes move in such as way that it becomes possible for protons to quantum tunnel. The work suggests that the motion needed is relatively short-ranged, although other researchers are also looking at whether long-range movement that extends throughout the enzyme plays a role in catalysis through quantum tunnelling. Much of the work that is being done in this area is hotly contested. Indeed, a related article in the same issue of Science by Stephen Benkovic and Sharon Hammes-Schiffer of Pennsylvania State University casts doubt on the findings, describing them as "at variance with other systems" and suggesting that there is more going on than was examined in the study. Nevertheless, the idea that protons as well as electrons can quantum tunnel is a striking one. And, as if that claim were not intriguing enough, the British researchers raise the possibility that short-range tunnelling in enzymes might be the result of evolutionary pressure. [If they mean "evolutionary" in the sense of biological¸ it would seem to have the cart before the horse. If biochemical reactions were not catalysed, there would be no life in the first place. As a Dr. Richard Wolfenden found, uncatalysed biochemical reactions could take millions, indeed up to a trillion years. So As Wolfenden himself pointed out, "Without catalysts, there would be no life at all, from microbes to humans,' . `It makes you wonder how natural selection operated in such a way as to produce a protein that got off the ground as a primitive catalyst for such an extraordinarily slow reaction'":

"All biological reactions within human cells depend on enzymes. Their power as catalysts enables biological reactions to occur usually in milliseconds. But how slowly would these reactions proceed spontaneously, in the absence of enzymes -minutes, hours, days? ... Dr. Richard Wolfenden .... In 1998, he reported a biological transformation deemed `absolutely essential' in creating the building blocks of DNA and RNA would take 78 million years in water. `Now we've found one that's 10,000 times slower than that,' Wolfenden said. `Its half-time - the time it takes for half the substance to be consumed - is 1 trillion years, 100 times longer than the lifetime of the universe. Enzymes can make this reaction happen in 10 milliseconds.' Wolfenden, along with co-authors ... published a report of their new findings ... in the ... Proceedings of the National Academy of Sciences. ... May 13. The report highlights the catalytic power of phosphatase enzymes to tremendously enhance the transformation rate in water of a specific group of biochemicals: phosphate monoesters. Protein phosphatase enzymes acting on these monoesters help regulate the molecular cross-talk within human cells, the cell signaling pathways and biochemical switches involved in health and disease. `We have esters floating around in our cells with all kinds of functions,' Wolfenden said. `Every aspect of cell signaling follows the action of the type of phosphatase enzyme that breaks down phosphate monoesters. Other phosphatases highlighted in the study for their catalytic power help mobilize carbohydrates from animal starch and play a role in transmission of hormonal signals.' As to the uncatalyzed phosphate monoester reaction of 1 trillion years, `This number puts us way beyond the known universe in terms of slowness,' he said. `(The enzyme reaction) is 21 orders of magnitude faster than the uncatalyzed case. And the largest we knew about previously was 18. We've approached scales than nobody can grasp.' ... `Without catalysts, there would be no life at all, from microbes to humans,' he said. `It makes you wonder how natural selection operated in such a way as to produce a protein that got off the ground as a primitive catalyst for such an extraordinarily slow reaction.' ... `The enzymes we studied in this report are fascinating because they exceed all other known enzymes in their power as catalysts. We've only begun to understand how to speed up reactions with chemical catalysts, and no one has even come within shouting distance of producing their catalytic power.'". (Lang L.H., "Without enzyme catalyst, slowest known biological reaction takes 1 trillion years, EurekAlert!, 5 May, 2003. My emphasis)

However, Dr. Wolfenden is a tad confused. Without life, there is no "natural selection". As Theodosius Dobzhansky, co-founder of Neo-Darwinism, pointed out, "Prebiological natural selection is a contradiction in terms":

"One way out of the problem would be to extend the concept of natural selection to the pre-living world of molecules. A number of authors have entertained this possibility, although no reasonable explanation has made the suggestion plausible. Natural selection is a recognized principle of differential reproduction which presupposes the existence of at least two distinct types of self-replicating molecules. Dobzhansky appealed to those doing origin-of-life research not to tamper with the definition of natural selection when he said: `I would like to plead with you, simply, please realize you cannot use the words `natural selection' loosely. Prebiological natural selection is a contradiction in terms.' [Dobzhansky T.G., in Fox S.W., ed., "The Origins of Prebiological Systems and of Their Molecular Matrices," Academic Press: New York NY, 1965, p.310] Bertalanffy made the point even more cogently: `Selection, i.e., favored survival of "better" precursors of life, already presupposes self-maintaining, complex, open systems which may compete; therefore selection cannot account for the origin of such systems' [von Bertalanffy L., "Robots, Men and Minds," George Braziller: New York NY, 1967, p.82]" (Thaxton C.B., Bradley W.L. & Olsen R.L., "The Mystery of Life's Origin: Reassessing Current Theories," [1984], Lewis & Stanley: Dallas TX, 1992, p.147. My emphasis)

After all, if there was such a things non-biological "natural selection" (especially so powerful that it could perform biochemical reactions without enzymes), then biological natural selection (and Darwinism) would be even more unfalsifiable that it already is! How could anyone tell if mutations were random if there was natural selection at the biochemistry level? That would be a case of `out of the frying-pan and into the fire for Darwinism, if it embraced non-biological `natural selection' to solve its origin of life problem!

I have added this quote to a new section of my "Problems of Evolution" book outline, PE 7. 4. 5. "Problems for all naturalistic origin of life theories ... Slowness of reactions without enzymes"]

Whether this suggestion proves to be weirder than quantum mechanics itself remains to be seen. ... [Actually, I don't think this suggestion is "weird" at all. Clearly something amazing is going on that can speed up a biochemical reaction (which is "absolutely essential in creating the building blocks of DNA and RNA") from "78 million years" down to "10 milliseconds"!]

PS: Here below is another quote (by an atheistic evolutionist, despite the title) about the central origin of life "chicken and egg' dilemma", that "all of the enzymes needed to catalyse gene expression are themselves produced by the expression of their genes," that is, "DNA and RNA are needed to make proteins, while proteins are needed to make DNA and RNA"!

Stephen E. Jones, BSc (Biol).
"Problems of Evolution"

"This process of protein synthesis is known as 'translation', since the genetic message is now being translated from the language of DNA and RNA (i.e. from the language of nucleic acids) into the language of proteins. The entire process of decoding a gene into a protein, involving both transcription (the production of the mRNA) and translation (use of the mRNA to make protein) is known as gene 'expression'. And remember that all of the enzymes needed to catalyse gene expression are themselves produced by the expression of their genes; and all the other types of RNA, such as tRNAs and the RNAs found in ribosomes, are produced by the transcription of genes that encode them. So DNA and RNA are needed to make proteins, while proteins are needed to make DNA and RNA, and also to assemble proteins. This presents us with a 'chicken and egg' type of dilemma: how could DNA and RNA (or any similar nucleic acid) have first formed and been replicated without proteins; or how could proteins have first formed without the DNA genes and mRNAs needed to encode them, and without the other proteins needed to catalyse their manufacture? That is really the central issue facing scientists trying to explain the origin of life on earth - how did self-replicating systems of genes encoding proteins that make new genes and proteins ... first arise?" (Scott A., "The Creation of Life: Past, Future, Alien," Basil Blackwell: Oxford UK, 1986, p.39. Ellipses original)

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