ch21 biochem

• ATP synthase is made up of two components. The F1 component contains the active sites and protrudes into the mitochondrial matrix. The F0 component is embedded in the inner mitochondrial membrane and contains the proton channel.
• Each enzyme has three active sites located on the three β subunits. Each β subunit is distinct in that each subunit interacts differently with the γ subunit
• The proton gradient generated by the oxidation of NADH and FADH2 is called the proton-motive force. This also powers ATP synthesis.
• ATP and ADP must bind to Mg2+ to function as substrates.
• ATP synthase catalyzes the formation of ATP from ADP and Pi . The reaction proceeds through a pentacovalent intermediate.
• The three catalytic β subunits of the F1 component can exist in three conformations:

  In the O (open) form, nucleotides can bind to or be released from the β subunit. In the L (loose) form, nucleotides are trapped in the β subunit. In the T (tight) form, ATP is synthesized from ADP and Pi in the absence of a proton gradient but cannot be released from the enzyme.
• Proton flow around the c ring powers ATP synthesis. Subunit a has two channels that reach halfway into the a subunit. One half channel opens to the intermembrane space and the other to the matrix.
• Protons enter the half-channel facing the proton-rich intermembrane space, bind to a glutamate or aspartate residue on one of the subunits of the c ring, and then leave the c subunit once it rotates around to face the matrix half channel.
• NADH = 10/4 =2.5 ATP

  FADH2 = 6/4 = 1.5 ATP
• In muscle, electrons from cytoplasmic NADH can enter the electron-transport chain by using the glycerol 3-phosphate shuttle.
• In heart and liver, electrons from cytoplasmic NADH are used to generate mitochondrial NADH in the malate-aspartate shuttle.
• The ATP-ADP translocase enables the exchange of cytoplasmic ADP for mitochondrial ATP.

  The translocase is powered by the proton-motive force,
• ADP must enter the mitochondria for ATP to leave.
• The binding of ADP from the cytoplasm favors eversion of the transporter to release ADP into the matrix . Subsequent binding of ATP from the matrix to the everted form favors eversion back to the original conformation, releasing ATP into the cytoplasm.
• 26 ATP are formed in oxidative phosphorylation, 4 come from glycolysis.
• Electrons do not flow through the electron-transport chain unless ADP is available to be converted into ATP.
• Inhibition of the electron-transport chain prevents oxidative phosphorylation by preventing the formation of the proton-motive force.