Mitrochondrial enzyme by KK Sahu sir

1) Introductione

(2) History

(3) Structure

(4) list of mitochondrial enzymas

a) enzymes of outer membrane
b) enzymes of outer chamber
c) enzymes of inner membrane
d)enzymes of inner chambes

(5)Mitochondrial enzymes
1 Subtypes and tissue distribution
2 Function
3 Substrate specificities
4 Clinical significance
5 Genetics

(6) Enzymes of CAC

(7) Enzymes of oxidative phosphorilation

(8) Electron carrior and complex.

(9) Respiratory chain inhibitors.

(10) Conclution

(11) refrences

1. MITOCHONDRIAL ENZYMES By KAUSHAL KUMAR SAHU Assistant Professor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )

2. Contents :- (1) Introductione (2) History (3) Structure (4) list of mitochondrial enzymas a) enzymes of outer membrane b) enzymes of outer chamber c) enzymes of inner membrane d)enzymes of inner chambes (5)Mitochondrial enzymes 1 Subtypes and tissue distribution 2 Function 3 Substrate specificities 4 Clinical significance 5 Genetics (6) Enzymes of CAC (7) Enzymes of oxidative phosphorilation (8) Electron carrior and complex. (9) Respiratory chain inhibitors. (10) Conclution (11) refrences

3. introduction ; 1) Mitochondria are sometimes described as "cellular power plants“ because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy . 2) The word mitochondrion comes from the Greek μίτος or mitos , thread + χονδρίον or chondrion , granule. 3) the mitochondrion has its own independent genome history; Kolliker (1850) first seen mitochondria in street muscle cells. Flemming (1882) named fila . Altman (1892) named Bioplast . Benda (1898) named mitochondria. Nass (1963) Observed DNA in mitochondria .

4. structure; A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins . [6] 1 . outer membrane :- It contains large numbers of integral proteins called porins 2.inner membrane space :- , the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol .   3.inner membrane :- ; Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable . 4.Cristae:- inner mitochondrial membrane, enhancing its ability to produce ATP. These folds are studded with small round bodies known as F 1 particles or oxysomes . 5.matrix:- The major functions include oxidation of pyruvate and fatty acids , and the citric acid cycle . STRUCTURE OF MITOCHONDRIA

5. Outer membrane enzymes *monoamine oxidase *rotenone insensitive NADH cyt -c- reductace *kynurenine hydroxylase thiokinase Outer chamber enzymes * adenylate kinase * nucieoside diphosphokinase List of mitochondrial enzymes;

6. Inner membrane enzymes *respiratory chain enzymes *ATP synthetase orxidase *succinate dehydrogenase * carnitine fatty acid acyl transferase Inner chamber enzymes *isocitrate dehydrogenase *fumerase *aconitase *citrate snythetase * alfa-keto acid dehydroge *beta-oxidation enzymes *L-malate hydrogenase *L-amino levuline synthatase *L-glutamate dehyrogenase

7. {1}enzymes of outer membrane Monoamine oxidase :- Contents; 1. Subtypes and tissue distribution:- 2. Function:- 3. Substrate specificities (1) Serotonin, melatonin, norepinephrine , and epinephrine are mainly broken down by MAO-A. (2) Phenethylamine and benzylamine are mainly broken down by MAO-B. (3) Both forms break down dopamine, tyramine , and tryptamine equally. 4.Clinical significance 5. Genetics

8. Nuclieoside diphosphokinase :- . enzymes of outer chember ;- enzymes that catalyze the exchange of phosphate groups between different nucleoside diphosphates . Function :- GTP + ADP → GDP + ATP Prokaryotic systems (2 ) Eukaryotic systems :

9. { 3}enzymes of inner membrane { 1} carnitine fatty acid acyl transferase :- Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine . In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (fats) for the generation of metabolic energy Bi ochemistry Biosynthesis - Role in fatty acid metabolism – Potential uses as a pharmaceutical Heart conditions Kidney disease and dialysis Effect in male infertility As an antidote in valproic acid poisoning As a weight loss supplyment

10. {4}enzymes of inner chamber Three stages of ceel respiration :- Oxidative decarboxylation [ pyruvate to acetyl co-A CAC/ TCA/ Acetyl co-A catabolism/ kreb ’ s cycle ETC/ ETS/ oxidative phosphorylation .

11. [a]CAC/ KREB ’ S CYCLE ENZYMES;

12. Substrates Products Enzyme Reaction type Comment Oxaloacetate + Acetyl CoA + H 2 O Citrate + CoA-SH Citrate synthase Aldol condensation irreversible, extends the 4C oxaloacetate to a 6C molecule Citrate cis - Aconitate + H 2 O Aconitase Dehydration reversible isomerisation cis -Aconitate + H 2 O Isocitrate Hydration Isocitrate + NAD + Oxalosuccinate + NADH + H + Isocitrate dehydrogenase Oxidation generates NADH (equivalent of 2.5 ATP) ROLE OF CAC ENZYEM ’ S

13. Oxalosuccinate α-Ketoglutarate + CO 2 Decarboxylation rate-limiting, irreversible stage, generates a 5C molecule α-Ketoglutarate + NAD + + CoA-SH Succinyl-CoA + NADH + H + + CO 2 α-Ketoglutarate dehydrogenase Oxidative decarboxylation irreversible stage, generates NADH (equivalent of 2.5 ATP), regenerates the 4C chain (CoA excluded) Succinyl-CoA + GDP + P i Succinate + CoA-SH + GTP Succinyl-CoA synthetase substrate-level phosphorylation or ADP → ATP instead of GDP→GTP, [7] generates 1 ATP or equivalent

14. Succinate + ubiquinone (Q) Fumarate + ubiquinol (QH 2 ) Succinate dehydrogenase Oxidation uses FAD as a prosthetic group (FAD→FADH 2 in the first step of the reaction) in the enzyme, [7] generates the equivalent of 1.5 ATP Fumarate + H 2 O L - Malate Fumarase H 2 O addition ( hydration ) L -Malate + NAD + Oxaloacetate + NADH + H + Malate dehydrogenase Oxidation reversible (in fact, equilibrium favors malate ), generates NADH (equivalent of 2.5 ATP)

15. 1)ACONITASE ;- Aconitase has an active [Fe 4 S 4 ] 2+ cluster, which may convert to an inactive [Fe 3 S 4 ] + form. ISOCITRATE DEHYDROGENASE :- Isozymes NADP + dependent Each NADP + -dependent isozyme functions as a homodimer : NAD + dependent The isocitrate dehydrogenase 3 isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit.

16. (3) FUMERASE :- MACHANISM OF FUMARASE Clinical significance Fumarase deficiency is characterized by polyhydramnios and fetal brain abnormalitie . In the newborn period, findings include severe neurologic abnormalities, poor feeding, failure to thrive, and hypotonia .

17. (4) BETA –OXIDATION ENZYMES :- Activation of fatty acids in the cytosol Transport of fatty acids into mitochondria ( carnitine shuttle ) 3. Beta oxidation proper in the mitochondrial matrix . (5) L- malate dehydrogenase BETA OXIDATION CYCLE

18. {2} OXIDATIVE PHOSPHORILASION ENZYMES

19. Photosynthetic electron transport chain of the thylakoid membrane .

20. Electron carriers F MN – 2) Coenzyme Q

21. 3) Heme – A prosthetic group of cytochromes . Heme contains an iron atom embedded in a porphyrin ring system. The porphyrin ring structure is planar. The iron atom of heme is usually bonded to two axial ligands , in addition to the 4 N of the porphyrin ring system.

22. 4) Cytochromes – Are proteins with heme prosthetic groups. . 2) Some cytochromes are part of large integral membrane complexes , each consisting of several polypeptides and including multiple electron carriers. . For example, hemes a and a 3 that are part of the respiratory chain complex IV are often referred to as cytochromes a and a 3 . Cytochrome c is instead a small, water-soluble protein, with a single heme group. 5) Iron-sulfur centers (Fe-S Electron transfer proteins may contain multiple iron-sulfur centers .  

23. R espiratory chain 1) Most constituents of the respiratory chain are embedded in the innen Mitochondria membrane (or in the cytoplasmic membrane of aerobic bacteria 2) Electrons are transferred from NADH to O 2 via multi-subunit inner membrane complexes I, III, & IV , plus coenzyme Q and cytochrome c . Within each complex, electrons pass sequentially through a series of electron carriers.

24. Complex Name No. of Proteins Prosthetic Groups Complex I NADH Dehydrogenase 46 FMN, 9 Fe-S centers Complex II Succinate-CoQ Reductase 5 FAD, cyt b 560 , 3 Fe-S centers Complex III CoQ-cyt c Reductase 11 cyt b H , cyt b L , cyt c 1 , Fe- S Rieske Complex IV Cytochrome Oxidase 13 cyt a, cyt a 3 , Cu A , Cu B

25. Respiratory chain inhibitors include the following :     (A) Rotenone (a common rat poison) blocks electron transfer in complex I.    (B) Antimycin A blocks electron transfer in complex III.     (C) Cyanide and carbon monoxide inhibit complex IV. C omplex I catalyzes oxidation of NADH, with reduction of coenzyme Q:   NADH + H + + Q � NAD + + QH 2 The initial electron transfers are:     NADH + H + + FMN � NAD + + FMNH 2     FMNH 2 + (Fe-S) ox � FMNH�  + (Fe- S) red + H + S uccinate Dehydrogenase of the Krebs Cycle   is also called complex II or Succinate-CoQ Reductase . .

26. Complex III accepts electrons from coenzyme QH 2 that is generated by electron transfer in complexes I and II. The structure and roles of complex III are discussed in the section on oxidative phosphorylation . Cytochrome c 1 , a prosthetic group within complex III, reduces cytochrome c , which is the electron donor to complex IV. C ytochrome oxidase (complex IV) carries out the following irreversible reaction: O 2 + 4 H + + 4 e - � 2 H 2 O So the ETC cycle has been completed.

27. REFERENCE 1.Advanced biology-Kent michael 2.Cell and molecular Biology- Gerald Karp 3. Geoffrey M.Cooper -The cell a moleculer approach. 4. molecular and cell biology- Lodish et.al. Websites: www.kbiotech.com www.wikipedia.com