disagreement about the total energy cost of mRNA translation. In addition to the one ATP per peptide required for capping the 5-prime end of the peptide, at least one GTP per peptide bond is required for initiation, two GTP per bond for elongation, and one GTP per peptide for termination. However, recent evidence suggests that one additional molecule of GTP is required for chain elongation (Schimmel, 1993), and hydrolysis of an additional GTP might be required during initiation and/or at the termination step as well. If hydrolysis of these additional high-energy bonds is proven correct, the net energy cost of protein synthesis alone will increase significantly from estimates made a decade ago.

In addition, there are a variety of other costs that are difficult to estimate. All of the additional sequences that are involved in, for example, synthesizing ''pre-proteins" and "pre-pro-proteins" and the costs of alternate splicing are not easy to quantify. In a sense, synthesizing and then removing these unused peptide sequences is wasted energy unless some as-yet-unknown energy advantage is discovered for this process. Similarly, the cost of synthesizing nonessential amino acids that are required for protein synthesis and the costs of posttranslational modifications are not known with certainty.

Further, the folding (Hartl, 1996) and the movement of the synthesized proteins to their sites of action (Rothman and Wieland, 1996) are highly energy-dependent processes. ATP-dependent mechanisms are required for polypeptide chain folding by heat-shock protein 70 and the chaperonin families of molecular chaperones (Hartl, 1996). Translocation across the membrane of the rough endoplasmic reticulum is an energy-dependent process, as is each transport step to the cis, medial, and trans Golgi compartments (Rothman and Wieland, 1996).