this phosphate group is missing in NAD+ and NADH regenerates NADP+, it is the NADPH that is oxidized and the substrate that is reduced. The NADPH is an effective donor of its hydride ion to other molecules for the same reason that ATP readily transfers a phosphate: in both cases the transfer is accompanied by a large negative free-energy change. One example of the use of NADPH in biosynthesis is shown in Figure 2–37.
The extra phosphate group on NADPH has no effect on the electron-transfer properties of NADPH compared with NADH, being far away from the region involved in electron transfer (see Figure 2–36C). It does, however, give a molecule of NADPH a slightly different shape from that of NADH, making it possible for NADPH and NADH to bind as substrates to completely different sets of enzymes. Thus, the two types of carriers are used to transfer electrons (or hydride ions) between two different sets of molecules.
Why should there be this division of labor? The answer lies in the need to regulate two sets of electron-transfer reactions independently. NADPH operates chiefly with enzymes that catalyze anabolic reactions, supplying the high-energy electrons needed to synthesize energy-rich biological molecules. NADH, by contrast, has a special role as an intermediate in the catabolic system of reactions that generate ATP through the oxidation of food molecules, as we will discuss shortly. The genesis of NADH from NAD+, and of NADPH from NADP+, occur by different pathways and are independently regulated, so that the cell can adjust the supply of electrons for these two contrasting purposes. Inside the cell the ratio of NAD+ to NADH is kept high, whereas the ratio of NADP+ to NADPH is kept low. This provides plenty of NAD+ to act as an oxidizing agent and plenty of NADPH to act as a reducing agent (Figure 2–37B)—as required for their special roles in catabolism and anabolism, respectively.
There are many other activated Carrier molecules in Cells
Other activated carriers also pick up and carry a chemical group in an easily transferred, high-energy linkage. For example, coenzyme A carries a readily transferable
Figure 2–37 NaDPH as a reducing agent. (a) The final stage in the biosynthetic route leading to cholesterol. as in many other biosynthetic reactions, the reduction of the C=C bond is achieved by the transfer of a hydride ion from the carrier molecule naDph, plus a proton (h+) from the solution.
(B) Keeping naDph levels high and naDh levels low alters their affinities for electrons (see panel 14–1, p. 765). This causes naDph to be a much stronger electron donor (reducing agent) than naDh, and naD+ therefore to be a much better electron acceptor (oxidizing agent) than naDp+, as indicated.
acetyl group in a thioester linkage, and in this activated form is known as acetyl CoA (acetyl coenzyme A). Acetyl CoA (Figure 2–38) is used to add two carbon units in the biosynthesis of larger molecules.
In acetyl CoA, as in other carrier molecules, the transferable group makes up only a small part of the molecule. The rest consists of a large organic portion that serves as a convenient “handle,” facilitating the recognition of the carrier molecule by specific enzymes. As with acetyl CoA, this handle portion very often contains a nucleotide (usually adenosine), a curious fact that may be a relic from an early stage of evolution. It is currently thought that the main catalysts for early life-forms—before DNA or proteins—were RNA molecules (or their close relatives), as described in Chapter 6. It is tempting to speculate that many of the carrier molecules that we find today originated in this earlier RNA world, where their nucleotide portions could have been useful for binding them to RNA enzymes (ribozymes).