14 May 2018 : Review article
Alkaloids, Nitric Oxide, and Nitrite Reductases: Evolutionary Coupling as Key Regulators of Cellular Bioenergetics with Special Relevance to the Human MicrobiomeGeorge B. Stefano12ACDEF*, Richard M. Kream3ACDEF
Med Sci Monit 2018; 24: REV3153-3158
Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of “morphinergic” signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.
Keywords: Morphine, Alkaloids, Nitric Oxide, Nitrite Reductases, Mitochondria, Evolution, Molecular
12 September 2022 : EditorialEditorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)
Med Sci Monit 2022; 28:e938365
16 September 2022 : Review articleEffects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...
Med Sci Monit In Press; DOI: 10.12659/MSM.938141
12 September 2022 : Clinical ResearchEffect of Vitamin D Concentration on Course of COVID-19
Med Sci Monit In Press; DOI: 10.12659/MSM.937741
29 August 2022 : Database AnalysisTranscriptome Analysis of Peripheral Blood Mononuclear Cells Response in Patients with Severe COVID-19 Reve...
Med Sci Monit 2022; 28:e937532
29 Sep 2022 : Animal ResearchEffect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap
Med Sci Monit In Press; DOI: 10.12659/MSM.937718
26 Sep 2022 : Clinical ResearchDistribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...
Med Sci Monit In Press; DOI: 10.12659/MSM.937987
26 Sep 2022 : Clinical ResearchLatency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing
Med Sci Monit In Press; DOI: 10.12659/MSM.937847
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292