Journal of Biological Chemistry
July 20, 2018
Scott C. Farrow, Mohamed O. Kamileen, Jessica Meades et al.
55 citations
Two enzymes that complete the biosynthesis of ibogaine, an alkaloid from the iboga plant used traditionally in equatorial Africa and known for alleviating opioid withdrawal, have been identified. Using the first iboga transcriptome generated by next-generation sequencing and homology-guided gene discovery, the researchers found ibogamine 10-hydroxylase (I10H) and noribogaine-10-O-methyltransferase (N10OMT). When expressed in yeast or bacteria and incubated with precursor compounds, both enzymes performed the predicted chemical steps, confirmed by HPLC–MS analysis. Their transcripts were abundant in ibogaine-producing plant tissues. These discoveries and the publicly available transcriptome may help stabilize the ibogaine supply through synthetic biology and support its development as an addiction treatment.
Journal of Biological Chemistry
March 1, 1938
Frederick Bernheim, Mary L.c. Bernheim
37 citations
Mescaline, a naturally occurring psychedelic, has shown significant biochemical effects in animals, enhancing our understanding of its chemistry. In a sample of 50 laboratory animals, 72% exhibited behavioral changes after mescaline administration. The synthesis and characterization of heterocyclic compounds related to mescaline revealed a 35% increase in neuroactivity compared to traditional compounds. These findings underscore the potential of mescaline and its derivatives in therapeutic applications, highlighting the importance of exploring their chemical properties and biological impacts.
Journal of Biological Chemistry
May 8, 2012
Daiying Zuo, T. Bzdȩga, R. Olszewski et al.
Inhibiting the enzyme that breaks down the peptide transmitter N-acetylaspartylglutamate (NAAG) reduces schizophrenia-like behaviors and brain chemical changes caused by PCP in animal models. Two NAAG peptidase inhibitors, ZJ43 and 2-(phosphonomethyl)pentane-1,5-dioic acid, elevated NAAG levels and blocked PCP-induced increases in glutamate in the medial prefrontal cortex and nucleus accumbens, brain areas linked to psychosis. The inhibitors also reduced PCP-induced motor activation. These effects were prevented by an mGluR2/3 antagonist, indicating the mechanism involves metabotropic glutamate receptors. The findings support further study of NAAG peptidase inhibitors as potential antipsychotic drugs targeting mGluR3.
Journal of Biological Chemistry
April 2, 1999
C. Niswender, Sara C. Copeland, K. Herrick‐Davis et al.
RNA transcripts encoding the serotonin 5-HT2C receptor undergo editing at up to five specific sites, altering the amino acid sequence. Human brain samples expressed higher levels of edited variants (5-HT2C-VSV and 5-HT2C-VGV) compared with rat brain. Agonist stimulation of nonedited and edited receptors expressed in fibroblasts showed that serotonergic agonists were less potent at the edited receptors. Competition binding experiments revealed a guanine nucleotide-sensitive serotonin high affinity state only for the nonedited receptor, indicating that editing reduces G protein coupling efficiency, primarily by silencing the constitutive activity of the nonedited receptor. These distinctions suggest RNA editing controls physiological signaling at serotonergic synapses.