Chapter 4
Molecular Asymmetry and Sterol Evolution W. David Nes and M. Venkatramesh
Downloaded by CORNELL UNIV on May 19, 2017 | http://pubs.acs.org Publication Date: August 5, 1994 | doi: 10.1021/bk-1994-0562.ch004
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, T X 79409-1061
Sterols are chiral natural products that form biomolecular complexes in cells. In this review, we examine the biomimetic and catalytic forces that may have acted to create -ex nihilo suiet subjecti- optical purity in sterol structure and stereochemistry. The causal factors that may have contributed to the maintenance and change in three-dimensional shape of sterols during evolution is also discussed. The recognition that life and biochemical change on planet Earth is based on the biological properties of simple asymmetric natural products (such as, amino acids and sugars (monocyclic)) has been the subject of thoughtful speculation for over a century (7,2). The origin and phylogeny of optical purity in these molecules and proteins has generated much discussion (3-6). We now consider a more complex class of compounds - isopentenoid polycycles. Specific isopentenoids, like amino acids, are vital to the survival and reproductive fitness of the cell (7). Two groups of amphiphilic polycycles are examined here: sterols (tetracycles) and hopanoids (pentacycles). Their study is of interest for several reasons: first, hopanoids have been found to be the most abundant biomolecules on Earth (8); second, hopanoids share structural and functional (as membrane inserts) equivalence with sterols in bacteria (9,10); third, there exist 512 stereoisomers (resulting from nine stereogenic centers) of tetrahymanol (a hopanoid) and 216 stereoisomers (resulting from eight stereogenic centers) of cholesterol, but only one stereoisomer is known to be synthesized of each compound in nature (7); fourth, sterols and triterpenes act as geomarkers and chemical fossils (77J. In this review we are also concerned with the causal forces, chemical and biochemical, that evolved specifically to make and break stereocenters in sterols. Several opposing views are examined as possible mechanisms for the origin of optically pure sterols and for introducing change in the sterol structure during evolution: Vitality (also referred to as the teleonomic or organization principle (7,12))is the principle where the degree of variation in point mutations leading to a change in sterol enzyme architecture and catalytic efficiency is controlled by the type and amount of reactant and product (and product utilization) in the cell, and by the reaction mechanism, not chance; Vitalism- is the principle in which variation in structure results from non-physiochemical force (13); Lamarckism- is the principle that structural
0097-6156/94/0562-0055$10.70/0 © 1994 American Chemical Society Nes; Isopentenoids and Other Natural Products ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
56
ISOPENTENOIDS AND OTHER NATURAL PRODUCTS
change results from heritable transmission of acquired characteristics and functions; Darwinism- is the principle that structural change in biomolecules is driven by random mutations in heritable material that give rise to new enzymes that catalyze different reactions. Natural selection of the biomolecules, according to Darwinism, operates at the population level by survival of the fittest organisms (75-75).
Downloaded by CORNELL UNIV on May 19, 2017 | http://pubs.acs.org Publication Date: August 5, 1994 | doi: 10.1021/bk-1994-0562.ch004
The Molecular Basis of Optical Purity The most apparent and universal chemical characteristic of natural products is their intramolecular asymmetry which affects the size, shape and function of the compound. Cells apparently have selected particular stereoisomers from pairs of antipodes, because, one of the antipodes has special functions (resulting from its 3-dimensional shape) that maintains life, uniquely. The general phenomenon of asymmetry is sufficiently important to evolution that it is frequently considered with models (Figure 1) that examine the origin and early development of life (3,5,76). Phylogenetic trees that show the origin of progenotes (first living entities) and branching lines of descent are continuing to undergo revision (17,18). The molecular paradigm for evolution shows the formation of racemic mixtures of compounds precede the formation of optically pure compounds: prebiotic systems being primitive, produced racemic mixtures abiotically and use the antipodes indiscriminately; biological systems being sophisticated, use biochemical recognition systems, e.g., binding of the molecule to protein or lipid, that discriminate (thereby, serving as the mechanism for selection) the order and arrangement of the molecule's constitution. Thus we begin our examination of molecular asymmetry and sterol evolution with a brief review of chemical terms. Asymmetry and molecular chirality (a term coined by Kelvin from the Greek word Khair meaning hand) are equivalent terms that refer to a geometrical property whereby an object cannot be superimposed on its mirror image by simple rotations and translations (cf. the example given in Human anatomy, Figure 2). That is, the object lacks specific symmetry properties- a plane, axis and center of symmetry (19). A n
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Downloaded by CORNELL UNIV on May 19, 2017 | http://pubs.acs.org Publication Date: August 5, 1994 | doi: 10.1021/bk-1994-0562.ch004
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