plimpton@batcomputer.UUCP (04/01/87)
This is a question from a physics-type to bio-types so apologies if this is
basic MicroBio 101 stuff.
Humans (all animals?) are asymmetric right vs. left. Namely, my heart is on
my left side, my appendix on the right, liver someplace, etc., etc. And a
nurse told me virtually everyone (99%+) is the same. My question is, given
that we all start from a one-cell symmetric egg, how do we all develop the
same asymmetry? It doesn't puzzle me (as much) that we are asymmetric at
all, but that we are all the same! That is, why aren't 50% of the people
around mirror images of me with their heart on the right side? In physics
lingo it seems like a violation of the law of parity. I guess what I'm
really asking is, that as the fetus cells are busily dividing along, how do
ones on the left know not just that it's time to become heart cells, but
that they're not on the right?
Wild guesses (in descending likelihood):
1. I know there's left and right-handed proteins and humans are all made
of only one kind (which?). So maybe this low-level asymmetry works its
way up thru the development to a heart on the left side? If so this is
pretty amazing, and you still need a mechanism to explain how it
happens ...
2. Maybe the egg isn't symmetric and as it sits in a gravity field,
different stuff is always on the right vs. the left and splitting into
more cells just accentuates the difference ...
3. The fetus develops in an asymmetric environment (Mom), so maybe the
fetus "hears" Mom's heart above and to the left and does the same ...
4. Coriolis effect (my favorite): Only people born in the northern
hemisphere have hearts on the left; southern hemisphere people on the
right ...
Related questions:
1. How soon is there left/right asymmetry in the growing fetus?
2. I assume there's a gene for right handed/brainedness vs. left and that
it controls the development of turning the left side of the brain into
something different than the right. So how do the chemicals or
proteins or whatever this gene makes know how to travel to the right
brain vs. the left, either before birth or after?
3. Since a small % of people do have their heart on the right side, how did
they get turned around? Are they complete mirror images of "normal"
people? Is this genetic (Republican parents) or just random chance?
Thanks in advance ...
Steve Plimpton ArpaNet: plimpton@cheme.tn.cornell.edu
UseNet: {cmcl2,shasta,uw-beaver,rochester}!cornell!batcomputer!plimptoneddy@boulder.UUCP (04/02/87)
{The question has to do with the origins of left/right asymmetry
in higher eukaryotes.
The answer has to do with the microtubule/cilia/flagella system.
Mutations that cause immobile cilia (Kartegener's syndrome) lead
to sterility (since the sperm cannot swim and the oviduct can not
transport oocytes) and respiratory problems, since the surface of
the lung is not kept clear of mucus, etc.
In addition, approximately 50% of these people have their internal
organs reversed. Since these mutations appear to affect only
cilia/flagella (differently sized versions of the same microtubule-
based structure), it appears that it is either the asymmetric beat wave
form of these subcellular organelles or some asymmetric aspect of
microtubules themselves that determines organismic asymmetry. It seems
unlikely that defect is in microtubules themselves, since microtubules
are intimately involved in essential functions (like mitosis), therefore
a likely guess is that ciliary beating early in the developing embryo
establishes a handedness for the embryo.
Enough biology for the moment, anyone seen a good movie lately?6065833@pucc.UUCP (04/03/87)
In article <586@batcomputer.tn.cornell.edu>, plimpton@batcomputer.tn.cornell.edu (Steve Plimpton) writes: says initally there is a symmetrical single celled egg. >guess what I'm >really asking is, that as the fetus cells are busily dividing along, how do >ones on the left know not just that it's time to become heart cells, but >that they're not on the right? Well, first off, while it may seem logical that a cell be symmetrical, this isn't the case at all. Cells are highly asymmetrical, but in ways we don`t understand very well. Which is why there is no answer yet to just HOW cells differentiate. The study of this is a pretty hot topic right now. Gravity may play a role, but I personally suspect the cues may be entirely in the cells' interiors, in the cytoplasm. There needn't necessarily be any direct genetic control. This leads to the business about handedness of physical asymmetries. Left/right handedness is thought to be partly inherited, but whether this is genetic or due to early environment isn't known. Left-handed children are far more likely to have had left-handed mothers. This suggests several things (in descending likelyhood): 1)"Maternal factors"; some developmental characteristics are due to something in the cytoplasm of the initial egg, irrespective of genetic content. This determines the direction in which snail shells coil, for example (a left/right-handedness!). or 2)Genetic control on the sex chromosomes, or 3)Left-handed mothers have a slight tendency (and some other mothers as well) to treat their children as lefties. >Related questions: > >1. How soon is there left/right asymmetry in the growing fetus? I don't really know, but believe it's very soon (first 5 divisions), and maybe even before fertilization. >assumes a gene for right/left See my #3 above. > So how do the chemicals or > proteins or whatever this gene makes know how to travel to the right > brain vs. the left, either before birth or after? They don't. They are just released, and the cell at the receiving end has somehow (this is the mystery!) decided it will receive these chemicals and act on them. >3. Since a small % of people do have their heart on the right side, how did > they get turned around? Are they complete mirror images of "normal" > people? Is this genetic (Republican parents) or just random chance? I know from personal experience that there are all degrees of this inversion. I've met someone with the entire circulatory system turned around, but the dige stive system in the right place. This is apparently still far more rare than the complete inversion case. There is evidence that this is completely random. An aside: I understand that persons with inverted organs were thought to be inviable, and expected to die shortly after birth, or be sterile, etc. This is generally not the case (except perhaps medical care was withheld in anticipation of the child's death). Also, some women have uteruses which curve back instead of forward, and this was supposed to be a cause of infertility (but isn't). What enlightened times we live in. My sources? I'm currently finishing my 4th year in Biology at Princeton; the above information is from recent genetics and evolution (dare I say that word on the net?) courses, and my own investigations. Una Smith 6065833@PUCC I thought signature files were silly until I realized I usually forget to identify myself. No longer. Please forgive my apparent rudeness.
werner@aecom.UUCP (04/04/87)
In article <586@batcomputer.tn.cornell.edu>, plimpton@batcomputer.tn.cornell.edu (Steve Plimpton) writes: > > Humans (all animals?) are asymmetric right vs. left. Namely, my heart is on > my left side, my appendix on the right, liver someplace, etc., etc. And a > nurse told me virtually everyone (99%+) is the same. My question is, given > that we all start from a one-cell symmetric egg, how do we all develop the > same asymmetry? Everything biological is assymetrical. Why do we metabolize only D-sugars, not L-sugars, or use only D-amino acids, and not their L enantiomers. Chemists cannot tell prochiral centers apart, but enzymes can. It turns out that the size of macromolecules ensures that they will always be assymetrical, and an assymetric molecule can react with a symmetrical one assymetrically. The molecule in question here is Dynein, the component of microtubules that provides the molecular motor. It interacts with polymerized tubulin to form the skeleton of cilia. Since tubulin has a direction, dynein binds only one way, and hence all cilia have a forward beat and a reverse beat. It turns out that this ciliary movement ensures that the heart will always be on the left side, and the liver on the right. The large intestine also undergoes a rotation to ensure that the rectum is on the left, and the ileocecal valve (and the appendix) on the right. Certain people are born without functional cilia. In addition to being sterile, and have chronic respiratory disorders, half of them have their internal organs reversed (i.e., without cilia to give direction, rotation IS random). The syndrome of immotile cilia due to defective Dynein arms is called Kartegner's Syndrome, and the reversed organs is referred to as 'Dextrocardia with Situs Invertus', and has been coined by the anatomist Francis Baker-Cohen as 'Vice versa viscera'. One of my medical puzzles dealt with left sided abdominal pain distant heart sounds (why?) and pulmonary congestion. It was a left sided appendicitis, and the other signs were hints. -- Craig Werner (MD/PhD '91) !philabs!aecom!werner (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) Everything's different. Nothing's changed. Well, only maybe slightly rearranged.
diaz@aecom.UUCP (04/04/87)
In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: > Everything biological is assymetrical. Why do we metabolize only > D-sugars, not L-sugars, or use only D-amino acids, and not their L > enantiomers. Chemists cannot tell prochiral centers apart, but enzymes > can. Last time I checked, all living organisms studied thus far have proteins made of L-amino acids. D-amino acids are found rarely, as part of antibiotics and in the cell walls of bacteria. Perhaps Craig is a bit more unique than we all thought. -- dn/dx = Dan Diaz (philabs!aecom!diaz) Department of Molecular Biology & Pizza Chemistry AECOM "Hold the E.coli"
werner@aecom.UUCP (04/04/87)
In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: > Everything biological is assymetrical. Why do we metabolize only > D-sugars, not L-sugars, or use only D-amino acids, and not their L > enantiomers? Oops, kind of got carried away: D-sugars is correct, but it's L-amino acids. Proving the rule, biology is more assymetrical than the included sentence. -- Craig Werner (MD/PhD '91) !philabs!aecom!werner (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "Coke is much more socially acceptable than self-mutilation."
honzo@4gl.UUCP (04/04/87)
in article <586@batcomputer.tn.cornell.edu>, plimpton@batcomputer.tn.cornell.edu (Steve Plimpton) says:
] 3. Since a small % of people do have their heart on the right side, how did
] they get turned around? Are they complete mirror images of "normal"
] people? Is this genetic (Republican parents) or just random chance?
I know of at least one person who has mirror body, i.e. it's not just the heart.It does not seem to be genetic. (I guess he move to and from a parallel universe
once :)
--
I_I( _ UUCP: ..mcvax!honzo@4gl
I I ) Honzo Svasek @ 4GL Consultants b.v. FIDO: Honzo Svasek @ 500/3336065833@pucc.UUCP (04/05/87)
In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: >Chemists cannot tell prochiral centers apart, but enzymes can. Not true; they can deduce their chirality by looking at the structure of derivatives of those molecules. > It turns out that the size of macromolecules ensures that they >will always be assymetrical, and an assymetric molecule can react with >a symmetrical one assymetrically. The second part of this sentence is true, both by the rules of logic, and common sense, but how does SIZE "ensure" anything? The odds are greater, when there are more asymmetrically bonding atoms involved, that a macromolecule be asymmetrical, but there need not be asymmetry. (And note the correct spelling of 'asymmetry,' please.) >'Cilia are the roots of all handedness.' Fine and well, but there is a deeper level still, which, since it isn't fully understood, is perhaps overlooked in medical school, but is addressed in some academic courses. Namely, given that cilia give a rotational orientation to a cell, how does the cell consistently decide to differentiate along a specific axis? There must be an internal mechanism. This may be in the cytoplasm (which is not a protein soup, contrary to popular belief). > It turns out that this ciliary movement ensures that the heart will >always be on the left side, and the liver on the right. This is one hypothesis. That the cilia are the deciding elements is not proven, just strongly suggested. > Certain people are born without functional cilia. In addition >to being sterile, and have chronic respiratory disorders, half of them >have their internal organs reversed (i.e., without cilia to give >direction, rotation IS random). If immotile cilia are the only possible cause of organ inversions, as you seem to suggest, anyone with inverted organs must have defective cilia, correct? But I know someone who does not have Kartegner's Syndrome, or anything else wrong with him, yet still has an inverted heart. This suggests to me that the mechanism is not as simple as you suggest. An aside: this condition refers primarily to which side of the heart the aorta, etc. are on. In true inversion, everything is a mirror image of a typical person's circulatory system. Some people, however, have their heart on the right side of their chest, but do not have inversion. > Craig Werner (MD/PhD '91) Does '91 mean you are a First year or Second year med. student, Mr. Werner? Personally, I prefer to avoid causing confusion by refering to myself as a junior or senior or whatever. After all, nothing is definite until it is over. Una Smith 6065833@PUCC I thought signature files were silly until I realized I usually forget to identify myself. No longer. Please forgive my apparent rudeness.
rengler@hvrunix.UUCP (04/05/87)
In article <586@batcomputer.tn.cornell.edu> plimpton@batcomputer.UUCP (Steve Plimpton) writes: >Humans (all animals?) are asymmetric right vs. left. Namely, my heart is on >my left side, my appendix on the right, liver someplace, etc., etc. And a >nurse told me virtually everyone (99%+) is the same. My question is, given >that we all start from a one-cell symmetric egg, how do we all develop the >same asymmetry? It doesn't puzzle me (as much) that we are asymmetric at >all, but that we are all the same! That is, why aren't 50% of the people >around mirror images of me with their heart on the right side? In physics >lingo it seems like a violation of the law of parity. I guess what I'm You've made some very interesting points, especially about the law of parity. I don't know why humans have evolved with this asymmetry, the fact is that we have. Since, somewhere in our evolutionary past, one of the forms began to develop asymmetrically, this is where you should look for the answer. After that point, it makes perfect sense that we would continue to show the same patterns of development, the ones developing as "mirror images" would be mutations of a sort. You also have to consider that there has to be some inherent asymmetry, due to the nature of our bodies (blood going in one side of the heart, coming out the other, etc.). Of course that doesn't explain why it favors one side or the other, just that it has to be one side. >really asking is, that as the fetus cells are busily dividing along, how do >ones on the left know not just that it's time to become heart cells, but >that they're not on the right? This is simple. Once the pattern has developed, it is easily reproducable with the body's biochemical mechanisms. >Wild guesses (in descending likelihood): ^^^^^^^^^^^^ Exactly! They are all pretty much wrong. > >1. I know there's left and right-handed proteins and humans are all made > of only one kind (which?). So maybe this low-level asymmetry works its The body uses L (left-handed) forms of amino acids, the D (right-handed) form of sugars (notably glucose), and B-DNA (a right-handed twisting). I very much doubt that this is the source of assymetry. Guesses 2,3, and 4 are just wild! Some biologist may just tear this opinion to pieces. This is the theory of a chemist with some biochemical knowledge. -- Rich Engler "The Wanderer" "Did I err?" -Groo ihnp4!bpa!vu-vlsi!hvrunix!rengler
werner@aecom.UUCP (04/07/87)
<2190@PUCC.PRINCETON.EDU>, 6065833@PUCC.PRINCETON.EDU (Una Smith) writes: > In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: > > >Chemists cannot tell prochiral centers apart, but enzymes can. > > Not true; they can deduce their chirality by looking at the structure > of derivatives of those molecules. Let me phrase this statement another way. H A prochiral center such as XCH has 2 Hydrogens that are identical. Y With a three dimensional model, it is easy to point to one in the pro-R and another in the pro-S, however, no reaction done by a chemist will differentiate between those two. Enzymes,however, will, pluck one 100% of the time, and the other, none. No mixture of enantiomers for enzymes - the same cannot be said of chemists. Note that a prochiral molecule is not chiral. Hence, there is no chirality to deduce. As for the rest of Una Smith's followup to my article, it's not worth my time to comment... -- Craig Werner (MD/PhD '91) !philabs!aecom!werner (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "The proper delivery of medical care is to do as much Nothing as possible"
cjh@petsd.UUCP (04/07/87)
[] In article <147@4gl.UUCP> honzo@4gl.UUCP writes: > >I know of at least one person who has mirror body, i.e. it's not just the heart.It does not seem to be genetic. (I guess he move to and from a parallel universe >once :) That must have been a Moebius trip. Regards, Chris -- Full-Name: Christopher J. Henrich UUCP: ...!hjuxa!petsd!cjh US Mail: MS 313; Concurrent Computer Corporation; 106 Apple St; Tinton Falls, NJ 07724 Phone: (201) 758-7288 Concurrent Computer Corporation is a Perkin-Elmer company.
plimpton@batcomputer.tn.cornell.edu (Steve Plimpton) (04/08/87)
Thanks to all who responded to my query on why all humans have the same left/right asymmetry. In a nutshell, your answer is that all of us (excepting those with Kartegner's Syndrome who also often have reversed organs) have cilia/microtubules/cytoplasm in our cells that are/is asymmetric the same way. This was news to me, so I am enlightened - but still have a couple of follow-up questions. My confusion likely comes from looking at this as a geometry problem and not a biological one, but here goes ... 1. It only makes sense, when looking at an object, to label one side the left and the other right, if it is already asymmetric top vs. bottom and front vs. back. Otherwise you can rotate it to reverse left and right and the object looks the same. So when eddy@boulder.Colorado.EDU (Sean Eddy) in <865@sigi.Colorado.EDU> writes (and others similarly) > ... it appears it is either the asymmetric beat wave > form of these subcellular organelles or some asymmetric aspect of > microtubules themselves that determines organismic asymmetry. > ... a likely guess is that ciliary beating early in the developing embryo > establishes a handedness for the embryo. does this mean that one could take a human egg and by examining its cilia/microtubule structure or motion (assuming you could look at it in sufficient microscopic detail), one could assign a unique top/bottom, front/back, left/right (TBFBLR) to it? And that *all* human eggs are the same in that respect? So that in essence every egg is a human in miniature with the same TBFBLR orientation as each other and adults? If this isn't so, then I'm still having trouble visualizing, when the embryo consists of a few cells (20 or 20,000 - I don't know) and there is a definable top/bottom and front/back, but not yet a left and right, how a cell on the left is in any different a chemical/biological environment than one on the right and hence senses it's the one that should become a heart. It doesn't (to me) seem enough to say (for example) all the cilia are beating towards the left at that point therefore that's where the heart will end up, because if the top or front had formed the opposite way (which it seems they could have if there wasn't a TBFBLR to start with), the cilia would be beating to the right. Any help here? 2. In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes > The molecule in question here is Dynein, the component of > microtubules that provides the molecular motor. It interacts with > polymerized tubulin to form the skeleton of cilia. Since tubulin > has a direction, dynein binds only one way, and hence all cilia > have a forward beat and a reverse beat. > It turns out that this ciliary movement ensures that the heart will > always be on the left side, and the liver on the right. I have no idea what tubulin is, but is its handedness a direct result of the handedness of amino acids and sugars? And if so, does this mean that in the organic soup bubbling on earth a few years ago, if the first (tubulin, amino acids, self-replicating gizmos, whatever) had been the other handed, that nature as we know it would be reversed? I.e. that we'd all have right-side hearts, 90% of us be left-handed, want to sleep on the other side of the bed, da Vinci would have painted Peter sitting on the other side of Christ in "The Last Supper", and so on ad infinitum? Thanks again ... Steve Plimpton ArpaNet: plimpton@cheme.tn.cornell.edu UseNet: {cmcl2,shasta,uw-beaver,rochester}!cornell!batcomputer!plimpton
lotto@wjh12.UUCP (04/08/87)
In article <1013@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: ><2190@PUCC.PRINCETON.EDU>, 6065833@PUCC.PRINCETON.EDU (Una Smith) writes: >> In article <1003@aecom.UUCP>, werner@aecom.UUCP (Craig Werner) writes: >> >> >Chemists cannot tell prochiral centers apart, but enzymes can. >> >> Not true; they can deduce their chirality by looking at the structure >> of derivatives of those molecules. > > the pro-R and another in the pro-S, however, no reaction done by a >chemist will differentiate between those two. Enzymes,however, will, >pluck one 100% of the time, and the other, none. No mixture of >enantiomers for enzymes - the same cannot be said of chemists. Craig, Any of the other chemists working on catalytic enantioselective methodology will be very disappointed to hear this. The bottom line is that prochiral centers can be modified selectively only in a chiral environment. Enzymes are certainly some of the most efficient chemical sources of these environments, but they are not the only ones. The source of chirality may be: a) external (environmental) as in a catalyst b) local as in a "chiral auxiliary" c) internal as in most diastereoselective technology Some examples include - Reaction Chiral element type Asymmetric Epoxidation Di-isopropyl tartrate esters a Modified Aldol Valinol or Norephedrine imides b OH-directed Chiral Allylic or Homoallylic c Hydrogenation Alcohol Type a) is the class that enzymes belong in. The ref. for the example above is J. Am. Chem. Soc. 102, 5974 (1980). There are a number of other examples as well. -- Gerald Lotto - Harvard Chemistry Dept. UUCP: {seismo,harpo,ihnp4,linus,allegra,ut-sally}!harvard!lotto ARPA: lotto@harvard.harvard.edu
agranok@udenva.UUCP (04/09/87)
In article <1013@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: > > H > A prochiral center such as XCH has 2 Hydrogens that are identical. > Y > With a three dimensional model, it is easy to point to one in >the pro-R and another in the pro-S... Can you make assignments such as R and S in this case? It all depends upon what your reference point is. Consider the following: H (1) | 0 0 / 0 0\ / \/ \ X Y H (2) Where X and H (2) are out of the screen and Y is into the screen. Also, have X be a higher precedence group than Y. Now, when viewed opposite hydrogen (2), the molecule has an R configuration, but when viewed opposite hydrogen (1), it has an S configuration. Maybe I'm not getting all of your terminology, but I thought that R and S configurations could only be assigned when there was a chiral center. A molecule can't be both R and S with respect to the same cen- ter within the *same* molecule. Of course, the same center can be R or S in different molecules. Could you please elaborate? -- Alex Granok hao!udenva!agranok "A slow sort of country!" said the Queen. "Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!"
eddy@boulder.UUCP (04/10/87)
In article <633@batcomputer.tn.cornell.edu> plimpton@batcomputer.UUCP (Steve Plimpton) writes: >does this mean that one could take a human egg and by examining its >cilia/microtubule structure or motion (assuming you could look at it in >sufficient microscopic detail), one could assign a unique top/bottom, >front/back, left/right (TBFBLR) to it? And that *all* human eggs are the same >in that respect? So that in essence every egg is a human in miniature with the >same TBFBLR orientation as each other and adults? > > If this isn't so, then I'm still having trouble visualizing, when the >embryo consists of a few cells (20 or 20,000 - I don't know) and there is a >definable top/bottom and front/back, but not yet a left and right, how a cell >on the left is in any different a chemical/biological environment than one on >the right and hence senses it's the one that should become a heart. It doesn't >(to me) seem enough to say (for example) all the cilia are beating towards the >left at that point therefore that's where the heart will end up, because if the >top or front had formed the opposite way (which it seems they could have if >there wasn't a TBFBLR to start with), the cilia would be beating to the right. >Any help here? OK, I'll try. First of all, remember that you asked a comparatively simple question to start. The question Craig and I answered was "why does the human heart almost always end up on the left side?" The answer we gave is a typical biology answer. A syndrome is known in humans in which the heart's position is randomized with respect to left and right. When you look for the specific genetic defect associated with this syndrome, the defect lies in the ciliary system. Therefore, says the biologist, the ciliary system determines the asymmetry of the heart with respect to left and right position in the body. One may also assume that the fact that cilia beat in one direction has some significance. But, to my knowledge, that's all we know and/or safely assume. So I can't say more than this. From that simple question, you naturally are asking a broader question, that of asymmetry in general. That's a large part of what developmental biologists are trying to answer, and far beyond the scope of my knowledge, at least in human development. (Side note of clarification: the asymmetry of the egg itself does not bear directly on the heart question. Cilia are expressed later in development, I believe.) So what I'm saying is, I can't explain human developmental biology. Neither can anyone else, for now. All that's known is bits and pieces, and some of the underlying themes. - Sean Eddy - Dept. of Molecular, Cellular, Developmental Biology - Univ. of Colorado, Boulder; Boulder, CO 80309 - - "Ph.D.'s are for suckers." -- from 'Ask Mr. Science'
werner@aecom.UUCP (04/11/87)
Anyone wishing to know the ins and outs of biological rotations
during development would be wise to read a book on Embryology. I
recommend the one by Moore.
Besides the fact that nature generally only uses one enantiomer
over another, any questions of WHY one was chosen over the other can
be explained down to finer details (cilia, the microtubules that make
up cilia, the tubulin and dynein that makes up microtubules), but
eventually one gets to the point where one just has to conclude: well,
it had to pick one.
As for right versus left. It is known that the first cell division
from the egg is non-symettrical nor the second. From the 4 cell stage
stage, there is already an putative top and an putative front. Topologists
can verify that means that right and left are constrained.
--
Craig Werner (MD/PhD '91)
!philabs!aecom!werner
(1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517)
"It doesn't even have to be a Pelvis."werner@aecom.UUCP (04/11/87)
In article <3432@udenva.UUCP>, agranok@udenva.UUCP (Alexander Granok) writes: > In article <1013@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: > > > > H > > A prochiral center such as XCH has 2 Hydrogens that are identical. > > Y > > With a three dimensional model, it is easy to point to one in > >the pro-R and another in the pro-S... > > Can you make assignments such as R and S in this case? It all depends upon I see that non-biochemists are troubled by the concept of prochirality. By definition, a prochiral molecule is a symmetric (i.e. achiral) molecule that would be made chiral if one of the identical atoms (Hydrogen in the above example) were replaced by a third atom, Z. It is true that the identity of the pro-R and pro-S hydrogen is absolutely ambiguous unless one knows the priority of the Z group in relation to X and Y, but for any given reaction where the products and reactants are known, it will be unambiguous. Where it is simple hydrogenation/dehydrogenation, the assignment is made by replacing one of the Hydrogens with Deuterium (first done experimentally by Frank Westheimer), usually as a Gedanken experiment. Finally, when I said that chemists cannot avoid a mixture of enantiomers during a chemical synthesis, while enzymes can be stereochemically specific, I did not preclude the possibility of chemists using and/or designing enzymes -- but I thought that went without saying. Obviously, to the nitpickers on the net, nothing goes without saying.... -- Craig Werner (MD/PhD '91) !philabs!aecom!werner (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "If you've heard this story before, don't stop me. I want to hear it again."
lotto@wjh12.UUCP (04/12/87)
In article <1025@aecom.UUCP> werner@aecom.UUCP (Craig Werner) writes: >In article <3432@udenva.UUCP>, agranok@udenva.UUCP (Alexander Granok) writes: > > I see that non-biochemists are troubled by the concept of >prochirality. By definition, a prochiral molecule is a symmetric >(i.e. achiral) molecule that would be made chiral if one of the identical >atoms (Hydrogen in the above example) were replaced by a third atom, >Z. > It is true that the identity of the pro-R and pro-S hydrogen >is absolutely ambiguous unless one knows the priority of the Z group in >relation to X and Y, but for any given reaction where the products and >reactants are known, it will be unambiguous. No. pro-R / S have a precise definition. It requires that you prioritize the two identical groups (may be H but also may be anything else) with respect to each other. The priorities w/ respect to the other (two) attachments are retained as in the original compound. It IS true that biochemical literature has been using stereochemical terminology in a bastardized fashion for some time, but I cite the original Cahn, Ingold, and Prelog articles and follow ups by Helmchen and Prelog as the definitive source of these rules. Chirality is another matter. See Mislow JACS (1974) for a treatment of symmetry in chemical structure as it applies to the current nomenclature. > Finally, when I said that chemists cannot avoid a mixture of >enantiomers during a chemical synthesis, while enzymes can be stereochemically >specific, I did not preclude the possibility of chemists using and/or >designing enzymes -- but I thought that went without saying. Obviously, >to the nitpickers on the net, nothing goes without saying.... For crying out loud, since when is tartaric acid an enzyme? How about binaps's or any of the hundreds of C2 reagents for hydroboration. S-valinol? Nor-ephedrine? Chiral phase transfer catalysts? The list goes ever on. I respect your ability as a biochemist, but with respect to synthetic organic chemistry, quite a bit of your commentary SHOULD have gone without saying. -- Gerald Lotto - Harvard Chemistry Dept. UUCP: {seismo,harpo,ihnp4,linus,allegra,ut-sally}!harvard!lotto ARPA: lotto@harvard.harvard.edu