|Lecture Notes: 21 January||
Last semester we finished off our discussion with the ATP Synthase (Complex V; F0F1 ATP synthase, text Figure 19-23f, a-e).
We now need to address the problem resulting from the system enabling the synthase to operate, the very tight membrane which allows virtually no polar or charged molecules to pass through, which means the ATP made is in the wrong compartment and potentially stuck. So how did nature deal with this problem resulting from the ancient incorporation of a bacterial symbiote transformed to an organelle? That is our next discussion:
Given the requirement for a very tight inner-mitochondrial membrane in order to maintain the proton electrochemical gradient, how do important charged molecules such as ATP and NADH get across the membrane?
ADP & ATP are obviously among the most important substances to transport into and out of the mitochondria. Adenine nucleotide translocase exchanges matrix ATP for cytosolic ADP in their magnesium-free forms. (text Figure 19-26) Note that in this exchange ATP4- leaves the matrix as ADP3- goes in, resulting in a net loss of (1-) for the matrix. This increases the charge gradient across the membrane, and thus must be driven by the mitochondrial proton gradient. Of course Pi must also be transported across the membrane with ADP to make ATP in the matrix. This is accomplished using another transporter which co-transports a dihydrogen phosphate and a single proton in an electroneutral process. Note the addition of these two processes is equivalent to moving one proton from the cytosol to the matrix, costing the gradient one proton (moving a negative charge out is equivalent to moving a positive charge out).
The net cost of providing an ATP to the cytosol is thus four protons: three to convert ADP + Pi to ATP and one to transport ATP out of, while bringing ADP and Pi into, the matrix. This accounts for the theoretical yield of ATP: (10 H+/NADH)/(4 H+/ATP) = 2.5 ATP/NADH. (Note that this means that bacteria may get more ATP (up to 38 ATP's instead of the 32 expected in mammals).
Reducing Equivalent Shuttles: In aerobic metabolism NADH from glycolysis must be regenerated to NAD+ in the mitochondria. Two shuttles are important in different tissues/organisms for this process:
The glycerol-3-P is then reoxidized to dihydroxyacetone-P by Flavoprotein dehydrogenase. This enzyme is situated on the inner mitochondrial membranes outer surface. It uses FAD to oxidize the glycerol-3-P to dihydroxyacetone-P, passing the electrons to CoQ (note the similarity to succinate DH, except for the location on the outer instead of the inner surface of the membrane). The organism can thus get 1.5 ATP equivalents for this NADH.
Last modified 22 January 2009