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This means that electrons have to be "pushed uphill" from Fe(II) to NAD(P) against the redox potential gradient (uphill pathway).
Based on the cotranscription of the diheme cytochrome c4 gene (cycA1) with those encoding the bc1 complex, it was proposed that electrons from the diheme cytochrome c4 take a thermodynamically uphill pathway via the bc1 complex to a NADH complex driven energetically by proton motive force [ 2, 12- 14] (see Figure 1).
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And fire travels faster and with more vigor uphill, making those pathways extremely flammable.
To return to the mechanical analogy, enzymes cannot make water flow uphill, although they can provide specific pathways for a downhill flow.
He told reporters after his remarks at a Center for Immigration Studies event that he predicts an uphill battle for any bill with a pathway to citizenship, but that he hasn't spoken to House Speaker John Boehner (R-Ohio) about whether it could be passed.
From there, some of the electrons feed the "downhill electron pathway" through c-cytochrome Cyc1 to aa3 cytochrome oxidase, some the "uphill electron pathway" that regenerates the universal electron donor NADH by the reverse electron flow through c-cytochrome CycA1--> bc1 complex-->ubiquinone pool-->NADH dehydrogenase.
For example, there were 319 pathways (64%) corresponding to overall reaction [3] that involved a large uphill step where Δ r G'm was 12.5 ± 5.4 kcal/mol (three standard errors).
Uphill indeed.
Uphill again.
But uphill!
He was hiking uphill.
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