BIOQUÍMICA E BIOLOGIA CELULAR António Ascensão, José Magalhães Krebs cycle, electron transport chain and oxidative phosphorylation Faculdade de Desporto, Universidade do Porto, 1º Ciclo, 1º Ano 2011_2012
Oxida'on Catabolism of proteins, fats and carbohydrates occurs in the three stages of cellular respiration. Stage 1: Oxidation of fatty acids, glucose and some amino acids yields acetyl-coa. Stage 2: Oxidation of acetyl groups via the TCA cycle includes four steps in which electrons are abstracted. Stage3: Electrons carried by NADH and FADH 2 are funneled into a chain of mitochondrial electron carriers, the respiratory chain, ultimately reducing O 2 to H 2 O. This electron flow drives the synthesis of ATP, the process of oxidative phosphorylation.
Outline Mitochondrial structure and func1on Pyruvate dehydrogenase ac1va1on Krebs cycle Electron transport chain Oxida1ve phosphoryla1on
Mitochondrial structure
Mitochondrial structure
Mitochondrial func'on Oxidative phosphorylation Together they account for most of the ATP made in the biosphere. Reduction of O 2 to H 2 O with electrons from NADH and FADH 2 The processes involve: Chemiosmotic theory Flow of electrons through chain of membrane bound carriers Trapping energy through proton pumping to create a proton gradient Discharge of proton gradient through ATP synthase to create ATP
Mitochondrial transport systems Major inner mitochondrial membrane transport systems for respiratory substrates and products. The phosphate translocase and the adenine nucleotide translocase move substrates for oxidative phosphorylation (ADP and Pi) into the mitochondrion and the product (ATP) out. The other transport systems move substrates and products for citric acid cycle oxidation into or out of the matrix, as dictated by the metabolic need of the cell.
Mitochondrial transport systems ATP/ADP
PDH complex activation
Bioenergetics Aerobic ATP production Krebs cycle (citric acid cycle) Pyruvic acid (3 C) is converted to acetyl- CoA (2 C) CO 2 is given off Acetyl- CoA combines with oxaloacetate (4 C) to form citrate (6 C) Citrate is metabolized to oxaloacetate Two CO 2 molecules given off Produces three molecules of NADH and one FADH Also forms one molecule of GTP Produces one ATP
Krebs Cycle CS IDH CDH
Krebs Cycle
Bioenergetics
Bioenergetics
Mitochondrial electron transport chain organization Summary of the flow of electrons and protons through the four complexes of the respiratory chain. Electrons reach CoQ via Complexes I and II. CoQH 2 serves as a mobile carrier of electrons and protons. It transfers electrons to Complex III, which transfers them to another mobile connecting link, cytochrome c. Complex IV transfers electrons from reduced cytochrome c to O 2. Electron flow through Complexes I, III and IV is accompanied by proton flow from the matrix to the intermembrane space. Electrons from fatty acid b-oxidation can also enter the respiratory chain though UQ.
Mitochondrial electron transport chain organization Multiprotein complexes in the respiratory assembly, showing the prosthetic groups associated with each complex. Complexes I-IV are involved in electron transport; complex V uses the energy derived from electron transport to synthesize ATP. The subscripts for the b cytochromes denote their spectral maxima. The two b hemes in complex III are bound in the same polypeptide chain.
Mitochondrial electron transport chain organization
Mitochondrial electron transport bioenergetics
Mitochondrial electron transport chain organization
Mitochondrial electron transport chain organization
Mitochondrial electron transport chain organization
Mitochondrial electron transport chain organization Complex III
Mitochondrial electron transport chain organization Complex IV
Mitochondrial electron transport pathway
Mitochondrial electron transport pathway
ATP synthesis F 1 F o
Modulation of ETC and oxidative phosphorylation
Ox Phosph regula'on
Brown fat provides heat by uncoupling oxidative phosphorylation from electron transport. Dinitrophenol is an uncoupling agent once used as a diet pill. In spite of warnings from Stanford scientists, some enterprising physicians started to administer dinitrophenol to obese patients without proper precautions. The results were striking. Unfortunately in some cases the treatment eliminated not only the fat but also the patients, and several fatalities were reported in the Journal of the American Medical Association in 1929. (E. Racker, A New Look at Mechanisms In Bioenergetics, p 155)