05 May 2005 : Case report
Mammalian morphine: de novo formation of morphine in human cells.
Chotima PoeaknapoMed Sci Monit 2005; 11(5): MS6-17 :: ID: 16152
Abstract
BACKGROUND: Morphine, the major alkaloid of opium of Papaver somniferum, is one of the strongest analgesic compounds known. "Endogenous morphine" has been long isolated and authenticated by mass spectrometry in trace amounts from animal and human specific tissue or fluids. The most widely accepted explanation presently is that morphine detected in human and animal tissue is of exogenous sources (e.g. dietary origin). MATERIAL/METHODS: The biosynthetic experiments were performed with human neurobalstoma cells (SH-SY5Y) and human pancreas carcinoma (DAN-G) cells. The application experiments were done in the presence of isotopically labeled potential precursors such as (18)O(2) and [ring-(13)C(6)]-L-tyrosine. Benzylisoquinoline alkaloids present in mammalian cells were identified by GC-MS/MS. RESULTS: Growth of the SH-SY5Y cells in the presence of (18)O2 led to [(18)O(2)]-labeled morphine and [(18)O(2)]-labeled reticuline, each had a molecular mass four mass units higher than if grown in (16)O(2), indicating the presence of two atoms of (18)O per molecule. DAN-G cells cultured in an (18)O(2) atmosphere produced (S)-[ (18)O(2)]-norlaudanosoline and (S)-[ (18)O(2)]-reticuline, each labeled with (18)O atoms at only two of the four possible positions. Feeding of [ring-(13)C(6)]-tyramine, (S)-[1-(13)C, N-(13)CH(3)]-reticuline and [N-CD(3)]-thebaine to SH-SY5Y cells led each to the labeling of morphine, as established by GC-MS/MS. CONCLUSIONS: Taken together, morphine, reticuline and norlaudanosoline are unequivocally biosynthesized by cultured human cells. The precursors of morphine in the human cell lines were conclusively shown to be oxygen, tyramine, reticuline and thebaine.
Keywords: Benzylisoquinolines - chemistry, Benzylisoquinolines - metabolism, Morphine - chemistry, Tetrahydropapaveroline - chemistry, Tetrahydropapaveroline - metabolism, Tyramine - chemistry, Tyramine - metabolism, Alkaloids - metabolism, Benzylisoquinolines - metabolism, Carbon Isotopes, Chromatography, Liquid, Gas Chromatography-Mass Spectrometry, Molecular Structure, Morphine - metabolism, Oxygen Isotopes, Spectrometry, Mass, Electrospray Ionization, Tetrahydropapaveroline - metabolism, Tyramine - metabolism
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
18 Mar 2024 : Clinical Research
Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative StudyMed Sci Monit In Press; DOI: 10.12659/MSM.944136
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
Most Viewed Current Articles
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952