A mechanism for molecular asymmetry

Summary The origin of the molecular asymmetry of biological systems has been speculated upon extensively, and has been the object of numerous inconclusive experimental studies. That circularly polarized light (CPL) might have been the cause of this asymmetry was suggested in 1874 (van't Hoff 1897; Le Bel 1874). During the daylight morning (AM) there is a significant component of left (L) CPL in skylight, which reverses to right (R) CPL in the afternoon (PM) (Wolstencroft 1985). The rates or photochemical reactions of LCPL and RCPL are different for the R (right) and S (left) forms of chiral molecules (Flores et al. 1977). At sunset the ambient temperature at the surface of the earth is approximately 10°C higher than at sunrise. Most chemical reactions proceed faster at higher temperatures and for each 10°C rise in temperature chemical reaction rates increase by a factor of 1.8–4.1 (Taylor 1925). It is proposed that the combination of these four factors, LCPL in the AM compared to the RCPL in the PM, the different rates of photochemical reaction of the R and the S forms of an R-S racemic mixture with RCPL (and LCPL), the higher PM temperature, and the faster reaction rates in the PM could lead to a substantial deviation from equality in the degradation and formation of R and S enantiomeric forms of chiral molecules.     

Analyses of polypeptides in the liver of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma by two-dimensional gel electrophoresis: identification of P29/6.8 as carbonic anhydrase III and triosephosphate isomerase.

1. Total cellular proteins from the livers of 4-, 16- and 52-week-old hepatitis- and hepatoma-predisposed Long-Evans Cinnamon (LEC) rats were compared to those from the livers of the corresponding control rats [Long-Evans Agouti (LEA) rats] by two-dimensional gel electrophoresis. 2. A polypeptide, p50/7.2 (molecular weight x 10(-3)/isoelectric point) was only found in the LEC rats, and the p43/6.4 component was greater and the p51/6.8 component was less in the LEC rats than in the LEA rats during aging. 3. A polypeptide, p29/6.8, was dramatically greater in 4-week-old LEC rats than in 4-week-old LEA rats. 4. By sequencing and Western blotting analysis, the marked differences in the level of the p29/6.8 component were found to be due to carbonic anhydrase III.     

Pegylation: a method for assessing topological accessibilities in Kv1.3.

Each subunit of a voltage-gated potassium channel (Kv) contains six putative transmembrane segments, S1-S6, and a cytosolic N-terminal recognition domain, T1. Although it is well-established that Kv channels are tetrameric structures, the protein-protein, protein-lipid, and protein-aqueous interfaces are not precisely mapped. The topological accessibility of specific amino acids may help to identify these border residues. Toward this end, a variant of the substituted-cysteine-accessibility method that relies on mass-labeling of accessible SH groups with a large SH reagent, methoxy-polyethylene glycol maleimide, and gel shift assay has been used. Pegylation of full-length Kv1.3, as well as Kv1.3 fragments, integrated into microsomal membranes, allows topological characterization of the 12 native cysteines (C1-C12), as well as cysteines engineered into a T1-T1 interface. Cysteines engineered into the T1-T1 interface had lower rates of pegylation than cytosolic-facing cysteines, namely, C5 in the T1 domain and C10-C12 in the C terminus.