The following outlines explain the MECHANISMS of 
   growth PROMOTION by REDUCTANTS and 

         ~~~  GRAND  SCHEME  OF  MANAGING 
 Carbohydrates, Fats, Proteins, Supplements 
 Glycolysis, Hexose Monophosphate Shunt, 
 Tricarboxylic Acid Cycle, Oxidative Detoxification 
 NADH, NADPH, GSH, Certain Phenols 
 myriad BETS 
 Synthesis, Energy Production, Reduction of Oxidants, 
 Various Reductases, Physiologic Controls, 
 Mixed Function Oxidases 

Proliferation of cells requires a high level of synthetic activity. Many synthetic processes require ample supplies of reducing equivalents. Alteration of the relative demand of each reductant consuming pathway will alter the final distribution of reducing equivalents. Diversion of reducing equivalents to energy production or to oxidant removal depletes the carrier pool. Depleted carrier pools result in decreased supplies for synthesis. Inhibition of synthesis inhibits proliferation. ~~~ KEY PROCESSES NECESSARY TO PROLIFERATION WHICH DEPEND ON REDUCTANTS ~~~ activation of FOLATE to tetrahydrofolate: needed to produce thymine from uracil etc. activation of THIOREDOXIN: needed to produce deoxyribonucleosides activation of ORNITHINE DECARBOXYLASE: needed to produce putrescine and polyamines activation of GLYOXALASE by reduced glutathione: needed to remove alpha-keto-aldehydes activation of beta-ketoacyl-ACP-REDUCTASE, crotonyl-ACP-REDUCTASE, other reductases: needed to synthesize fatty acids activation of beta-hydroxy-beta-methylglutaryl- CoA-REDUCTASE: needed to synthesize turpenoids and cholesterol ~~~ DISEASES ASSOCIATED WITH ~~~ PROLIFERATION & SYNTHESIS & REDUCTANT DEPENDENCY = ALLERGIES: humoral cellular = INFECTIONS: viral inclusion bacterial fungal parasitic = NEOPLASMS: benign malignant ~~~ "OXIDATION-REDUCTION POTENTIALS IN BACTERIOLOGY AND BIOCHEMISTRY" ~~~ by LF HEWITT, 6th Ed, E. & S. LIVINGSTONE LTD., 1950 TOPICS: oxidation-reduction processes electrode potentials and polarography redox indicator methods effects of pH biologic electron/hydrogen carriers metabolic reductant production systems lag phase versus log growth phase peroxide resistance bactericidal dyes, mold products, quinones redox potentials of different bacteria redox potentials and virulence ~~~ REFERENCES BY ALBERT SZENT-GYORGYI, MD, PhD, NI ~~~ BIOELECTRONICS - A STUDY IN CELLULAR REGULATION, DEFENSE, AND CANCER 1968, Academic Press THE LIVING STATE - WITH OBSERVATIONS ON CANCER 1972, Academic Press THE LIVING STATE AND CANCER 1978, Marcel Dekker TOPICS DISCUSSED: - semiconductor characteristics of hydrated proteins - pools of exchangeable hydrogen carriers - how primitive and dividing cells require an abundance of reductants - phenol oxidases and peroxidases as defense systems against infection in higher plants - physiologic effects of ratios of alphaketoaldehydes to thiols and to amines - methylglyoxal as growth regulator - mechanism of glyoxalase activation by reduced glutathione BIOCHEMICAL PECULIARITIES OF TUMORS WHICH CAUSE INTERNAL REDOSIS: 1) glucose / insulin receptors overabundant 2) hexose monophosphate shunt upregulated 3) glycerol-3-phosphate dehydrogenase deficient 4) cysteine sequestration upregulated 5) glutathione peroxidase deficient BIOCHEMICAL ADVANTAGES OF REDOSIS WHICH FAVOR TUMOR GROWTH AND SURVIVAL: 1) ensure sufficient hydrogen donors for synthesis 2) toggle transcription factors and growth factors towards mode 3) enhance antioxidant protection against environment 4) enhance resistance to oxyradical attack by killer cells 5) maintain apoptosis triggers in mode ~~~ HOW TO DIVERT REDUCING EQUIVALENTS TOWARDS ENERGY PRODUCTION ~~~ EXERCISE - - - - - ADP activates mitochondrial ETC function increases perfusion RIBOFLAVIN - - - - precursor to FAD oxidoreductases THYROID & DHEA - - both induce G3PDH QUINONES - - - - - shuttle reductants to cytochromes HYDROGEN PEROXIDE - activates cytochromes OXYGEN - - - - - - activates cytochrome A COPPER - - - - - - ensures adequate cytochrome A LIGAND DETOX * - - ensures active cytochrome A AMMONIA DETOX - - - ensures active carbonyl carriers MANGANESE - - - - - ensures adequate mitochondrial SOD * HS- CN- NN- CO ~~~ HOW TO DIVERT REDUCING EQUIVALENTS TOWARDS OXIDANT QUENCHING PATHWAYS ~~~ OXYRADICALS (bad choice): radiation, selenium deficiency, toxic metals, iron overload or quinone overdose HYDROGEN PEROXIDE: IV-H2O2, PO-H2O2, PO-MgO2 ozone, quinones, autoregeneration LIPID PEROXIDES: auto-oxidation of PUFA's, ene reaction of singlet oxygen OXIDES OF CHLORINE: ClO2 HClO HClO2 HClO3 HClO4 ULTRAVIOLET BLOOD IRRADIATION: photoreduction consumes reductants singlet oxygen produces peroxides and quinones produces vitamin D a redifferentiator COPPER: activates many endogenous oxidases SELENIUM: activates glutathione peroxidase pathway GLUTATHIONE: activates glutathione peroxidase pathway activates reductive antioxidant family activates oxidant sensitive immunoreceptors ~~~ HOW EXCESS ACCUMULATION OF REDUCTANTS OCCURS ~~~ CAUSES: MECHANISMS: overeating - - - - - - - - substrates for NADPH production inactivity - - - - - - - - depressed reductant consumption hypothyroidism - - - - - - depressed reductant consumption depressed GPDH shuttling DHEA deficiency - - - - - elevates G6PDH activity cortisol excess - - - - - elevated gluconeogenesis insulin insensitivity - - elevated glucose Se deficiency - - - - - - failure of glutathione peroxidase failure of T4 to T3 conversion Cu deficiency - - - - - - failure of numerous oxidases carbon monoxide - - - - - blocks Hb and CytA hydrogen sulfide - - - - - blocks CytA and other Cu enzymes xenobiotic exposure - - - depletes glutathione induces quinone reductases ~~~ HOW TO STARVE THE SUPPLY SIDE ~~~ LOW CALORIE DIET FASTING EXERCISE CORRECT HYPERGLYCEMIA HYDRAZINE SULFATE GLUCOCORTICOID AVOIDANCE G6PDH DEFICIENCY DHEA SILVER XENOBIOTIC AVOIDANCE MAGADOSE REDUCTANT AVOIDANCE