- Topic: Coupled reactions and synthesis. Biochemical processes move downhill in free energy: they too must follow the laws of physics. To see how, we'll explore generic mechanisms of reaction coupling and a few key examples of synthesis powered by that ultimate activated carrier, ATP.
- Reading: Big Alberts, sections on reaction coupling and activated carriers (pp. 81-91 in the 4th ed.), as well as tidbits on DNA synthesis (pp. 239, 242-243), and protein synthesis (p. 339).
We managed to get a pretty concrete sense of how a non-equilibrium (i.e., typical) ATP concentration could be coupled to a bio-synthetic reaction, forcing the latter to proceed in an unfavorable direction. To that end, we considered in detail an example from Big Alberts Ch. 2, which is representative of some critical biosyntheses:
A-H + B-OH --> A-B + H20
The cell forces this reaction to proceed in two steps.
B-OH + ATP <--> B-Pi + ADP (fwd rate a, reverse rate b)
A-H + B-Pi <--> A-B + Pi (fwd rate c, reverse rate c)
First, ATP is hydrolyzed (very favorable) in a reaction that releases ADP and adds a phosphate group to B, forming a compound we'll abbreviate as B-Pi. But B-Pi is itself "activated" in being out of equilibrium with more favorable potential products, especially the free form of Pi. (Regarding activation, see summary April 18, 2012 meeting http://biops-pgh.blogspot.com/2012/05/biops-weds-4182012-meeting-here-was.html) The release of Pi is then enzymatically coupled to the formation of A-B.
The preceding qualitative explanation can be made more precise by modeling the steady state of the two coupled reactions assuming reactants A-H, B-OH, and ATP are added and products A-B, ADP, and Pi are removed. Using the rate constants from above, one finds
d[A-B]/dt = a[B-OH][ATP] - b[B-Pi][ADP],
in terms of the steady-state concentrations. Our basic question of whether A-B can in fact be synthesized is equivalent to whether the sign of this derivative is positive. The sign will be positive for a sufficiently large [ATP]/[ADP] ratio. Of course, "sufficiently large" will depend on the particular system (i.e., all rate constants) - qualitatively, on how unfavorable the synthesis of A-B truly is.
In brief, then, synthesis proceeds by harnessing energy from some carrier, which can be coupled to the desired synthesis in a clever step-wise fashion.
A very interesting example is DNA synthesis during replication, drawing on Ch. 5 from Big Alberts. In this case, the carrier is the "incoming" nucleotide tri-phosphate itself, which makes sense. The interesting part is that the need for potential error correction (i.e., removal of an incorrect base and attachment of correct base) actually dictates that replication should occur in the 5' to 3' direction. As illustrated in a lovely figure in big Alberts (5-11 in my edition), if the other direction were used the phosphate groups of the incoming nucleotide would not be available to power the required attachment.
