Porphyrins Regulate the Metabolic and Endocrine System: Role in Generation of Warburg Phenotype, Endogenous Digoxin Synthesis and Metabolic Syndrome X with Type 2 Diabetes Mellitus
Objectives: Actinidic archaea have been related to the pathogenesis of metabolic syndrome x. An actinide dependent shadow biosphere of archaea and viroids has been described in metabolic syndrome x with type 2 diabetes mellitus. Actinidic archaea have a mevalonate pathway and are cholesterol catabolizing. They can use cholesterol as a carbon and energy source. Archaeal cholesterol catabolism can generate porphyrins via the cholesterol ring oxidase generated pyruvate and GABA shunt pathway. Archaea can produce a secondary porphyria by inducing the enzyme heme oxygenase resulting in heme depletion and activation of the enzyme ALA synthase. Porphyrins have been related to metabolic syndrome x and type 2 diabetes mellitus. The role of archaeal porphyrins in regulation of cell functions, metabolism and endocrine function is discussed. Porphyrins play a key role in the generation of the Warburg phenotype, endogenous digoxin synthesis and metabolic syndrome x with type 2 diabetes mellitus.
Methodology: The following groups were included in the study: - metabolic syndrome x with cerebrovascular thrombosis and coronary artery disease. There were 10 patients in each group and each patient had an age and sex matched healthy control selected randomly from the general population. The blood samples were drawn in the fasting state before treatment was initiated. Plasma from fasting heparinised blood was used and the experimental protocol was as follows (I) Plasma + phosphate buffered saline, (II) same as I + cholesterol substrate, (III) same as II + rutile 0.1 mg/ml, (IV) same as II + ciprofloxacine and doxycycline each in a concentration of 1 mg/ml. The following estimations were carried out: - Cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroxide, pyruvate, ammonia, glutamate, succinate, glycine, delta aminolevulinic acid and digoxin. The study also involved estimating the following parameters in the patient population- hexokinase, porphyrins, pyruvate, glutamate, ammonia, succinic acid, serine, glycine, HMG CoA reductase, cytochrome C, blood ATP and heme oxygenase.
Results: Plasma of control subjects showed increased levels of the above mentioned parameters with after incubation for 1 hour and addition of cholesterol substrate resulted in still further significant increase in these parameters. The plasma of patients showed similar results but the extent of increase was more. The addition of antibiotics to the control plasma caused a decrease in all the parameters while addition of rutile increased their levels. The addition of antibiotics and rutile to the patient’s plasma produced the same changes but the extent of change was more in patient’s sera as compared to controls. There was upregulated archaeal porphyrin synthesis in the patient population which was archaeal in origin as indicated by actinide catalysis of the reactions. The cholesterol oxidase pathway generated pyruvate which entered the GABA shunt pathway. This resulted in synthesis of succinate and glycine which are substrates for ALA synthase. The study showed the patient’s blood had increased heme oxygenase activity, increased serine, glycine, succinic acid and porphyrins. The hexokinase activity was high. The pyruvate, glutamate, ammonia, GABA and succinic acid levels were elevated indicating blockade of PDH activity, and operation of the GABA shunt pathway. The cytoC levels were increased in the serum indicating mitochondrial dysfunction suggested by low blood ATP levels. This was indicative of the Warburg’s phenotype. The HMG CoA reductase activity was high indicating cholesterol synthesis. The RHCD population had values similar to the patient population. The LHCD population had opposite values. Conclusion: An actinide dependent shadow biosphere of archaea and viroids in metabolic syndrome x with coronary and cerebrovascular diseases. The porphyrins can contribute to the pathogenesis of metabolic syndrome x with coronary and cerebrovascular diseases. Porphyrin synthesis is crucial in the pathogenesis of these disorders. Porphyrins may serve as regulatory molecules modulating immune, neural, endocrine, metabolic and genetic systems. The porphyrins photo-oxidation generated free radicals can produce immune activation, produce cell death, activate cell proliferation, produce insulin resistance and modulate conscious/quantal perception. Porphyrins can regulate hemispheric dominance. The archaeal porphyrins functions as key regulatory molecules with mitochondrial benzodiazepine receptors playing an important role.
Key words: Actinide; Archaea; Porphyrins; GABA shunt; Peripheral benzodiazepine receptor; Delta aminolevulinic acid; Metabolic syndrome x; Type 2 diabetes mellitus; Coronary artery disease; Cerebrovascular disease
Eckburg P.B., Lepp, P.W., & Relman, D.A. (2003). Archaea and Their Potential Role in Human Disease. Infect Immun, 71, 591-596.
Smit, A., & Mushegian, A. (2000). Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway.Genome Res, 10(10), 1468-84.
Puy, H., Gouya, L., & Deybach, J.C. (2010). Porphyrias. The Lancet, 375(9718), 924-937.
Kadish, K.M., Smith, K.M., & Guilard, C. (1999). Porphyrin Hand Book. Academic Press, New York: Elsevier.
Gavish, M., Bachman, I., Shoukrun, R., Katz, Y., Veenman, L., Weisinger, G., & Weizman, A. (1999). Enigma of the Peripheral Benzodiazepine Receptor. Pharmacological Reviews, 51(4), 629-650.
Richmond, W. (1973). Preparation and Properties of a Cholesterol Oxidase from Nocardia Species and Its Application to the Enzymatic Assay of Total Cholesterol in Serum. Clin Chem, 19, 1350-1356.
Snell, E.D., & Snell, C.T. (1961). Colorimetric Methods of Analysis (Vol. 3A). New York: Van NoStrand.
Glick, D. (1971). Methods of Biochemical Analysis (Vol. 5). New York: Interscience Publishers.
Colowick, Kaplan, N.O. (1955). Methods in Enzymology (Vol. 2). New York: Academic Press.
Van der Geize R., Yam, K., Heuser, T., Wilbrink, M.H., Hara, H., & Anderton, M.C. (2007). A Gene Cluster Encoding Cholesterol Catabolism in a Soil Actinomycete Provides Insight into Mycobacterium Tuberculosis Survival in Macrophages. Proc Natl Acad Sci USA, 104(6), 1947-52.
Francis, A.J. (1998). Biotransformation of Uranium and Other Actinides in Radioactive Wastes. Journal of Alloys and Compounds, 271(273), 78-84.
Schoner, W. (2002). Endogenous Cardiac Glycosides, a New Class of Steroid Hormones. Eur. J. Biochem, 269, 2440-2448.
Vainshtein, M., Suzina, N., Kudryashova, E., & Ariskina, E. (2002). New Magnet-Sensitive Structures in Bacterial and Archaeal Cells. Biol Cell, 94(1), 29-35.
Tsagris E.M., de Alba, A.E., Gozmanova, M., & Kalantidis, K. (2008). Viroids, Cell Microbiol, 10, 2168.
Horie, M., Honda, T., Suzuki, Y., Kobayashi, Y., Daito, T., & Oshida, T. (2010). Endogenous Non-Retroviral RNA Virus Elements in Mammalian Genomes, Nature, 463, 84-87.
Kurup, R., & Kurup, P.A. (2009). Hypothalamic Digoxin, Cerebral Dominance and Brain Function in Health and Diseases. New York: Nova Science Publishers.
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