BIOLOGIC OXIDATION

ENERGI (ATP)

Source of ATP :1. Glycolysis.2. Krebs Cycle. 3. Oxidative Phosphorylation. Ox-red reactions O2 accept single electron

Ox-red reactions O2 accept single electronROS (radical or non radical)Cell damage linked to at least 100 deseasesCa, CV disorders, neurologic disordersAnti oxidantNatural & vitaminsBIOLOGIC OXIDATION

Oxidation-reduction potentialOxidation : the removal of electronsReduction : the gain of electronsRedox potential (E0) : the free energy change is proportionate to the tendency of reactants to donate or accept electronsRedox potential of a system (Eo) is compared with the potential of the hidrogen electrodeBiologic systems E0 expressed at PH 7 and electrode potential of H : 0,42 volts

SystemEO voltsH+/H2NAD+/ NADHLipoate; ox / redAcetoacetate/ 3 hydroxybutyratePyruvate/ lactateOxaloacetate/ malateFumarate/ succcinateCytochrome b; Fe3+/Fe2+Ubiquinone; ox/redCytocrome c1; Fe3+/Fe2+Cytocrome a; Fe3+/Fe2+Oxygen/ water -0.42-0.32-0.29-0.27-0.19-0.17+0.03+0.08+0.10+0.22+0.29+0.82

Enzymes in ox-redCalled oxidoreductases (class I), classified into 4 groups:- oxidases- dehydrogenases- hydroperoxidases- oxygenases

OxidasesCatalyzing the removal hydrogen and using oxygen as a acceptor form water or hydrogen peroxideSome oxidases contain copper and others are flavoproteinsCytochrome oxidase ( cyt.a.a3 ) :heme protein contain Cuterminal component of respiratory chaincontain two molecules of heme as prosthetic group and Cu

Flavoprotein enzyms contain FMN or FAD as prosthetic groupsFMN and FAD are formed in body from riboflavinThey are tightly bound to their apoenzymes but not covalentlyExampels: L-amino acid oxidase (in kidney), xanthine oxidase (in intestinal, kidney, liver), aldehyde oxidase (in liver) and glucose oxidase (in fungus)Oxidases

Dehydrogenases Can not use oxygen as a hydrogen acceptorPerforming two main functions: 1.transfer hydrogen in a coupled oxidation reduction reactionspecific for their substrates, but utilize common coenzymesuseful in enabling oxidative process to occur in the absence of oxygen2.components in respiratory chain transfer electron from substrate to oxygen

Dehydrogenases link NADUsing NAD+ or NADP+ as a coenzymeThese coenzyme are formed in body from niacin-freely and reversibly dissociate from their apoenzymes-NAD linked D-ase: oxidative pathways of metabolism (glycolysis, krebs cycle, respiratory chain)-NADP linked D-ase: characteristically in reductive synthesis (fatty acid synthesis, steroid synthesis and PMP-shunt)

Dehydrogenases link riboflavinUsing FMN and FAD as a coenzyme-more tightly bound to their apoenzymes -most of them are concerned with electron transport in / to resp chain-NADH D-ase carrier of electrons between NADH and components of higher redox potential-succinate D-ase, acyl Co-A D-ase, glycerol 3 P D-ase transfer electrons directly from substrate to resp. chain

Cytochromes as dehydrogenase Classified as dehydrogenases, except for cytochrome oxidase-as carriers of electrons from flavoproteins to cytochrome oxidase in the resp chain-exampels: cyt b, c1, c, a, a3 (resp chain) and cyt P 450, b5 (endoplasmic reticulum)

Hydroperoxidases Using hydrogen peroxide or an organic peroxide as substrateTwo type : -peroxidase -catalaseProtecting against harmful peroxides Peroxides generate free radicals disrupt membranes and cause cancer and atherosclerosis

PeroxidasesReducing peroxides using various electron acceptors (ascorbate, quinones, cyt c):H2O2 + AH2 2H2O + AFounding in milk, leukocytes, platelets, erythrocytes and other tissues involved in eicosanoid metabolismGlutathione peroxidase, containing selenium destruction of H2O2 and lipid hydroperoxidases protecting membrane lipids and Hb

Catalase

Using hydrogen peroxide as electron donor and electron acceptor:2 H2O2 2H2O + O2In addition to possessing peroxidase activity, it is able to use one of H2O2 as a substrate (electron donor) and another of H2O2 as an oxidant (electron acceptor)Founding in blood, bone marrow, mucous membranes, kidney and liver

OxygenasesCatalyzing the direct transfer and incorporation of oxygen into a substrateDivided into two subgroups: 1.Dioxygenases / oxygen transferaseIncorporating both atoms of oxygen into substrate: A + O2 AO2 2. MonooxygenasesMixed function oxidases and hydroxylases incorporate only 1 atom of oxygen into substrate, the other oxygen is reduced to water

MONOOXYGENASESNeed an additional electron donor / cosubstrate ( Z ):A-H + O2 + ZH2 A-OH + H2O + ZCytochromes P450 are monooxygenases (as cosubstrate ) important for detoxification of many drugs and for hydroxylation of steroids NADH and NADPH donate reducing equivalents for the reduction of cyt P450

Cytochrome P 450 Mitochondrial cyt P450 systems in steroidogenic tissues biosynthesis of steroid hormones from cholesterolMitochondrial cyt P450 systems in kidney metabolism of vitamin DMitochondrial cyt P450 systems in liver biosynthesis of bile acid

Superoxide free radicals (O2-)Generated from transfer of a single electron to O2It is formed reduced flavin, are reoxidized univalently by molecular oxygenSuperoxide dismutase in aerobic organisms removal O2- , the reaction: O2- + O2- + 2H+ H2O2 + O2Superoxide can reduce oxidized cyt c: O2- + cyt c (Fe3+) O2 + cyt c (Fe2+)Exposure to an atmosphere of 100% oxygen causes an adaptive increase in superoxide dismutase

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