|MadSci Network: Biochemistry|
Introduction Chemical isomers are molecules that have the same chemical formula (the same number and types of atoms) but have different structural formulae (different arrangements of those atoms). In general, isomers fall into two broad categories: structural isomers and stereoisomers. Structural isomers, are molecules in which the atoms are arranged in different patterns about the bonds. The bonds, themselves may also be different. The difference in structural formulae can be simple - subtle changes in the arrangements around common bonds, such as with iso-propanol and n-propanol (Figure 1, I/II) – or more obvious, such as with propanol and methyl ethyl ether (Figure 1, I/II vs. III). Figure 1: n-propanol (I), isopropanol (II), methyl ethyl ether (III) Stereoisomers isomers take several forms but have one property in common. They are isomers in which the pattern of bonds is the same, only the geometric positioning of the atoms differs. Stereoisomers will commonly fall into two types: those with geometric variations about a double bond (called ‘cis-trans isomers’) and those with geometric changes in the positioning of substituent atoms about a core atom (called enantiomers). There are also conformational and rotational isomers, which I won’t discuss here. A common biological example of cis-trans isomers are the all-trans retinal and 11-cis retinal (Figure 2), while alpha- and beta- D-glucose are common forms of enantiomeric isomers (Figure 3). Figure 2: Retinal isomers, cis-11 retinal (a), all-trans retinal (b) Figure 3: Glucose enantiomers, beta-D-glucose and alpha-D-glucose. Note the different arrangement of the atoms around the carbon attached to the green and red oxygens. Furthermore, a very large molecule with a complex three dimensional shape, may have the ability to take on multiple ‘shapes’ due to its flexibility. In such a case, the different forms are called ‘topoisomers’ (topological isomers). These are most common in polymer and protein chemistry. And now…the answer Isomers of all types are biologically abundant. Their importance comes, primarily, from two significant facts. First, virtually every biologically important molecule has one or more isomers. This is due, in part, to the necessary complexity of those molecules, which require numerous different types of atoms (a minimun of carbon, oxygen, hydrogen and often nitrogen, phosphorus and others) and will commonly contain a mixture of single and double bonds. Second, evolution, in almost all cases, has favoured the use of one isomer for a given purpose over the use of the others that exist. This second fact is more easily understood if you think that the molecules selecting the isomer to use (invariably proteins of some kind), are also isomers themselves and therefore it is not surprising that they have a ‘built-in’ bias. Thus, isomers are important because our entire biology, and that of every organism on the planet, is built on them. This dependence come in many forms, but invades every aspect of our body as you can see from some examples below. Our vision requires a protein called rhodopsin (itself an isomer, as are all proteins). Rhodopsin, however, has a small helper molecule -- cis-11 retinal, which is made from Vitamin A. Cis-11 retinal is converted to all-trans retinal (Figure 4) when exposed to light. Therefore, the light energy is absorbed during the retinal ‘isomerization’ (conversion between isomers). It is then given off to the protein and transported through the visual system to enable us to see. Figure 4: Light-induced isomerization of cis-11 retinal to all-trans retinal Another very common biological difference produced by isomers is with that of starch versus cellulose. Both starch and cellulose are polymers of (1,4) D-glucose, yet one (starch) is the principle dietary component of every culture on earth (whether from corn, wheat, rice, potato…) while cellulose is the principle structural component of a large portion of the world’s plant-life and is indigestible to most animals (except with the help of microorganisms or insects). What is the difference between the two? The glucose monomers used in their construction are enantiomers. Starch is composed of alpha-D-glucose while cellulose is composed of beta-D-glucose (Figure 5). Clearly, isomers play an important part in the world! Figure 5a: The simplified structures of starch, an alpha-(1,4) glucose polymer (A), and cellulose, a beta-(1,4) glucose polymer (B) In modern times and technologies, humans desire to create drugs that will help us overcome pain, allergies, psychological problems, infection, and many other medical conditions. Many, if not most, of these drugs will interact with proteins -- either receptors on cell membranes or enzymes. Such proteins are highly specific in recognizing their targets and therefore drugs must be made carefully to mimic such targets. This included creating the correct isomer, as only one isomer will be functional. Often, for technical reasons, a drug will be made in what is called a ‘racemic’ mixture, where both isomers exist in the solution. Then, the two isomers will be separated, if possible. The separation is important because, not only is one isomer generally ineffective, but that isomer may also be harmful. It is occasionally the case that side-effects from drugs come from isomeric impurities (of course, there are other reasons for side-effects also). These are but a few examples of the importance of isomers. As you can see, without isomers, life as we know it would not exist. References 1) Figures 1,2 4 were acquired from Wikipedia, searching for: Isomers 2) There is a good discussion of starch and cellulose at the London South Bank University web site (where I acquired the components of figure 5): Starch Cellulose 3) Frank R. Gorga has a nice, basic web course in isomers using CHIME demonstrations (Internet Explorer only - requires the CHIME plugin). 4) Elmhurst College has a discussion of glucose (where I got Figure 3). 5) A discussion of the biological importance of ‘chirality’ and isomers can be found in virtually all organic chemistry or biochemistry text books such as: Biochemistry by Donald Voet, Judith Voet. J.Wiley&Sons, 2004, 3rd ed. or Lehninger Principles of Biochemistry by Albert L. Lehninger, David L. Nelson, Michael M. Cox. W H Freeman & Co, 2004, 4th ed.
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