Specific and general pathway etc(new)2013
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Transcript of Specific and general pathway etc(new)2013
Introduction to metabolism. Specific and general pathways
of carbohydrates, lipids and protein metabolism
METABOLISM
The series of changes that a substance undergoes after absorption from the gastrointestinal tract where by it is used for synthesis of some of the tissue components or is broken down or otherwise altered and eliminated from the body through urine, feces, sweat or respiration.
CATABOLISM AND ANABOLISM
The process by which it is used in the synthesis of tissue components are referred to as “anabolism”
And the process by which it is broken down into simpler products are referred to as “catabolism”
METABOLIC PATHWAYSThis is process of substance convertion in some
part of metabolism.
They can be :1.Aliphatic(glycolysis, -oxidation of fatty acids)
2.Cyclic(Kreb’s cycle, urea synthesis cycle)
3.Unbranched (Pentose pathway of glucose oxidation).
TYPES OF REACTIONEXERGONIC REACTION
(ENERGY LIBERATING)
ATP + H2O → ADP + PHOSPHATE + 34 KJ/MOLE
ENDERGONIC REACTION
(ENERGY REQUIRING)
ADP + PHOSPHATE -+34 KJ/MOL ATP + H20
The modern views on the biological oxidation
All the enzymes involved in this process of biological oxidation belong
to the major class of oxidoreductases 1. OxidasesAH2 + O2 —————— ——> A + H2O Cytochrome oxidase, which is the terminal component
of ETC, belongs to this category. It contains heme and is described under the components of ETC.
2. Aerobic Dehydrogenases AH2 + O2 ----—> A + H2O2. These enzymes are flavoproteins and the product is
usually hydrogen peroxide.
3. Anaerobic DehydrogenasesAH2 (reduced) + B (oxidised) → A (oxidised) + BH2 (reduced)
- NAD+ linked dehydrogenases AH2 + NAD+ → A + NADH + H+
- FAD-linked Dehydrogenases - Cytochromes 4. Hydroperoxidases (All these enzymes use H2O2 as a
reactant )a)Peroxidase: H2O2 + AH2 —(peroxidase)——> 2H2O + Ab) Catalase 2H2O2 -—----(catalase)— —> 2H2O + O2
5. Oxygenases These are enzymes which catalyse reactions where
oxygen is transferred and incorporated into a substrate a) Mono-oxygenases A-H + O2 + BH2 —(hydroxylase)—»
A-OH + H2O + Bb) Di-oxygenases A + O2 → AO2
Citric acid cycle
supplies NADH and FADH2 to
the electron transport
chain
Electrons of NADH or FADH2 are used to reduce molecular oxygen to water.
A large amount of free energy is liberated.
The electrons from NADH and FADH2 are not transported directly to O2 but are transferred through series of electron carriers that undergo reversible reduction and oxidation.
The resulting distribution of protons generates a pH gradient and a transmembrane electrical potential that creates a protonmotive force.
The flow of electrons through carriers leads to the pumping of protons out of the mitochondrial matrix.
ATP is synthesized when protons flow back to the mitochondrial matrix through an enzyme complex ATP synthase.
The oxidation of fuels and the phosphorylation of ADP are coupled by a proton gradient across the inner mitochondrial membrane.
THE ELECTRON TRANSPORT CHAINSeries of enzyme complexes (electron carriers) embedded in the inner mitochondrial membrane, which oxidize NADH2 and FADH2 and transport electrons to oxygen is called respiratory electron-transport chain (ETC).The sequence of electron carriers in ETC
cyt bNADH FMN Fe-S Co-Q Fe-S cyt c1 cyt c cyt a cyt a3 O2
succinate FAD Fe-S
High-Energy Electrons: Redox Potentials and Free-Energy Changes
In oxidative phosphorylation, the electron transfer potential of NADH or FADH2 is converted into the phosphoryl transfer potential of ATP.
Phosphoryl transfer potential is G°' (energy released during the hydrolysis of activated phos-phate compound). G°' for ATP = -7.3 kcal mol-1
Electron transfer potential is expressed as E'o, (also called redox potential, reduction potential, or oxidation-reduction potential) require 0.34 EV for 1 macroergic bond.
E'o (reduction potential) is a measure of how easily a compound can be reduced (how easily it can accept electron).
All compounds are compared to reduction potential of hydrogen wich is 0.0 V.
The larger the value of E'o of a carrier in ETC the better it functions as an electron acceptor (oxidizing factor).
Electrons flow through the ETC components spontaneously in the direction of increasing reduction potentials.
E'o of NADH = -0.32 Evolts (strong reducing agent)E'o of O2 = +0.82 Evolts (strong oxidizing agent)
Important characteristic of ETC is the amount of energy released upon electron transfer from one carrier to another.This energy can be calculated using the formula:
Go’=-nFE’o
n – number of electrons transferred from one carrier to another; F – the Faraday constant (23.06 kcal/volt mol); E’o – the difference in reduction potential between two carriers.When two electrons pass from NADH to O2 :
Go’=-2*96,5*(+0,82-(-0,32)) = -52.6 kcal/mol
And 43.4 kcal/mol (FADH2).
• Mobile coenzymes: ubiquinone (Q) and cytochrome c serve as links between ETC complexes
• Complex IV reduces O2 to water
Components of electron-transport chain are arranged in the inner membrane of mitochondria in packages called respiratory assemblies (complexes).
THE RESPIRATORY CHAIN CONSISTS OF FOUR COMPLEXES
cyt bNADH FMN Fe-S Co-Q Fe-S cyt c1 cyt c cyt a cyt a3 O2
succinate FAD Fe-S
I
III
II
IV
I
II
III IV
Transfers electrons from NADH to Co Q (ubiquinone) Consist of: - enzyme NADH dehydrogenase (FMN - prosthetic group) - iron-sulfur clusters. NADH reduces FMN to FMNH2. Electrons from FMNH2 pass to a Fe-S clusters. Fe-S proteins convey electrons to ubiquinone. QH2 is formed.
Complex I (NADH-ubiquinone oxidoreductase)
The flow of two electrons from NADH to coenzym Q leads to the pumping of four hydrogen ions out of the matrix.
Complex II (succinate-ubiquinon oxidoreductase)
Transfers electrons from succinate to Co Q. Form 1 consist of: - enzyme succinate dehydrogenase (FAD – prosthetic group) - iron-sulfur clusters. Succinate reduces FAD to FADH2. Then electrons pass to Fe-S proteins which reduce Q to QH2
Form 2 and 3 contains enzymes acyl-CoA dehydrogenase (oxidation of fatty acids) and glycerol phosphate dehydrogenase (oxidation of glycerol) which direct the transfer of electrons from acyl CoA to Fe-S proteins.
Complex II does not contribute to proton gradient.
Complex III (ubiquinol-cytochrome c oxidoreductase)
Transfers electrons from ubiquinol to cytochrome c. Consist of: cytochrome b, Fe-S clusters and cytochrome c1. Cytochromes – electron transferring proteins containing a heme prosthetic group (Fe2+ Fe3+).
Oxidation of one QH2 is accompanied by the translocation of 4 H+ across the inner mitochondrial membrane. Two H+ are from the matrix, two from QH2
Complex IV (cytochrome c oxidase)
Transfers electrons from cytochrome c to O2. Composed of: cytochromes a and a3. Catalyzes a four-electron reduction of molecular oxygen (O2) to water (H2O): O2 + 4e- + 4H+ 2H2O
Translocates 2H+ into the intermembrane space
•Proposed by Peter Mitchell in the 1960’s (Nobel Prize, 1978)
•Chemiosmotic theory: electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane
Mitchell’s postulates for chemiosmotic theory
1. Intact inner mitochondrial membrane is required
2. Electron transport through the ETC generates a proton gradient
3. ATP synthase catalyzes the phosphorylation of ADP in a reaction driven by movement of H+ across the inner membrane into the matrix
The Chemiosmotic Theory
• ATP must be transported to the cytosol, and ADP and Pi must enter the matrix
• ADP/ATP carrier, adenine nucleotide translocase, exchanges mitochondrial ATP4- for cytosolic ADP3-
• The exchange causes a net loss of -1 in the matrix (draws some energy from the H+ gradient)
• Phosphate (H2PO4-) is transported into matrix in symport
with H+. Phosphate carrier draws on pH.
• Both transporters consume proton-motive force
Active Transport of ATP, ADP and Pi Across the Inner Mitochondrial Membrane
The most important factor in determining the rate of oxidative phosphorylation is the level of ADP.
The regulation of the rate of oxidative phosphorylation by the ADP level is called respiratory control
Respiratory control
REGULATION OF OXIDATIVE PHOSPHORYLATION
Coupling of Electron Transport with ATP SynthesisElectron transport is tightly coupled to phosphorylation.
ATP can not be synthesized by oxidative phosphorylation unless there is energy from electron transport.
Electrons do not flow through the electron-transport chain to O2 unless ADP is phosphorylated to ATP.
Important substrates: NADH, O2, ADP
Intramitochondrial ratio ATP/ADP is a control mechanism
High ratio inhibits oxidative phosphorylation as ATP allosterically binds to a subunit of Complex IV