Regulation of the interconversion of the phosphorylated and nonphosphorylated forms of pyruvate dehydrogenase in rat adipose tissue by insulin48-50 and in rat heart, liver, and kidney by long-chain fatty acids51 has been reported. Insulin apparently increases the proportion of the nonphosphorylated form of pyruvate dehydrogenase, and this effect is antagonized by adrenaline and by adrenocorticotrop-(50) S.

A model has been constructed using computer graphics for human renin based on the sequence derived from that of the gene and the 3-dimensional structure defined at high resolution for other homologous aspartic proteinases. Human renin can adopt a 3-dimensional structure close to that of other aspartic proteinases, in which amino acids corresponding to intron-exon junctions in the gene are at surface regions in the 3-dimensional structure. As expected, the essential catalytic residues are retained and the nearby residue 304 is alanine as in the mouse sequence, supporting the idea that Asp 304 of other aspartic proteinases may contribute to the low pH of their optimal activity. There are interesting differences at subsite S; which may contribute to the specificity of human renin. Certain residues at the surface of the enzyme adjacent to the active site cleft are unique to renins and may play a role in recognition and binding of angiotensinogen.

Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabinol (HHC). A new grouping, the 1‐methyl‐4‐phenylbutyloxy C‐3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.

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The synthetic approach to prostaglandins via bicyclo-[2.2.1]heptane derivatives, which has previously been 10