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The MALATE-ASPARTATE SHUTTLE gets reducing equivalents (electrons) from cytosolic NADH into the mitochondria so that 3 ATPs can be made
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Basic Concepts in Biochemistry
REGULATION
The rate of oxidative phosphorylation is controlled by the supply of ADP and phosphate Assuming that oxygen is available and that there is a supply of NADH- or FADH2-generating substrates, the activity of oxidative phosphorylation is determined by the availability of ADP If ADP is available and there is enough phosphate around (there usually is), the ADP and Pi are converted to ATP If not, not
P/O RATIOS
These are the numbers of ATP equivalents made per 2 electrons passed down the electron transport chain NADPH: P/O FADH2: P/O Succinate (with Acetate: P/O 3 2 rotenone present): P/O 25
The P/O ratio is the number of ATPs made for each O atom consumed by mitochondrial respiration The P stands for high-energy phosphate equivalents, and the O actually stands for the number of O2 s that are consumed by the electron transport chain The full reduction of O2 to 2 H2O takes 4 electrons Therefore, 2 electrons reduce of an O2 The oxidation of NADH to NAD and the oxidation of FADH2 to FAD are both 2-electron oxidations O can be read as the transfer of 2 electrons It s not quite as obscure as it sounds2 To figure out a P/O ratio3 you have to figure out two things the P and the O The P is easy if you ve learned to count ATPs made by various metabolic pathways The P is the net number of ATPs made by the metabolism of the substance you re dealing with The O is a little harder Here you must figure out how many times 2 electrons have been passed down the electron transport chain For each NADH or each FADH2 made during the metabolism of your substance, 1 O is consumed as 2 electrons are passed down the chain
2 It probably is as obscure as it sounds Remember O chain 3
transfer of 2 electrons down the entire
Pronounced pee to oh, pee over oh, or pee oh all are used
Electron Transport and Oxidative Phosphorylation
In the presence of the inhibitor rotenone (to prevent the oxidation of NADH by the electron transport chain), succinate can be metabolized only to fumarate, producing an FADH2 in the process Succinate FAD fumarate FADH2
The oxidation of the FADH2 makes 2 ATPs and consumes 1 O The P/O for succinate is 2 In the absence of rotenone, the NADH that is made from the conversion of succinate to oxaloacetate can be oxidized by the electron transport chain The metabolism of succinate then becomes Succinate FAD fumarate FADH2
Fumarate H2O malate Malate NAD oxaloacetate NADH H Net: Succinate FAD H2O NAD oxaloacetate FADH2 NADH
In this case, succinate metabolism to oxaloacetate produces 5 ATPs from the oxidation of the NADH and FADH2 2 from the FADH2 and 3 from the NADH Two O s are consumed, 1 for each of the NADH and FADH2 molecules The P/O is then 5/2 25 Thus the P/O can be a nonintegral number Just one more Let s do acetate Before it can be metabolized, acetate must be activated in a reaction that uses 2 ATP equivalents4 Acetate CoA ATP acetyl-CoA ADP PPi
Acetyl-CoA metabolized through the TCA cycle yields 3 NADH, 1 FADH2, and 1 GTP a total of 12 ATP equivalents (3 from each NADH, 2 from each FADH2, and 1 GTP 12 in all) Four O s are used, 1 for each NADH and FADH2 The P in this case is 10 (12 2 for the activation of acetate to acetyl-CoA) The P/O 10/4 25 P/O ratios for anything else are calculated in the same way
UNCOUPLERS
Allow protons back into the mitochondria without making any ATP Stimulate oxygen consumption
4 For reactions that make PPi (pyrophosphate), the PPi is rapidly hydrolyzed to 2 Pi in the cell, so we ll consider the formation of PPi to use 2 high-energy-phosphate bonds
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