Hh Oh Oh

FIGURE 13-11 Nucleoside triphosphates in RNA synthesis. With each nucleoside monophosphate added to the growing chain, one PP, is released and hydrolyzed to two Ph The hydrolysis of two phospho-anhydride bonds for each nucleotide added provides the energy for forming the bonds in the RNA polymer and for assembling a specific sequence of nucleotides.

molecules results in the sliding of myosin fibrils along actin filaments (see Fig. 5-32), which translates into macroscopic contraction of the muscle fiber.

As we noted earlier, this production of mechanical motion at the expense of ATP is one of the few cases in which ATP hydrolysis per se, rather than group transfer from ATP, is the source of the chemical energy in a coupled process.

Transphosphorylations between Nucleotides Occur in All Cell Types

Although we have focused on ATP as the cell's energy currency and donor of phosphoryl groups, all other nu-cleoside triphosphates (GTP, UTP, and CTP) and all the deoxynucleoside triphosphates (dATP, dGTP, dTTP, and dCTP) are energetically equivalent to ATP. The free-energy changes associated with hydrolysis of their phosphoanhydride linkages are very nearly identical with those shown in Table 13-6 for ATP. In preparation for their various biological roles, these other nucleotides are generated and maintained as the nucleoside triphos-phate (NTP) forms by phosphoryl group transfer to the corresponding nucleoside diphosphates (NDPs) and monophosphates (NMPs).

ATP is the primary high-energy phosphate compound produced by catabolism, in the processes of gly-colysis, oxidative phosphorylation, and, in photosyn-thetic cells, photophosphorylation. Several enzymes then carry phosphoryl groups from ATP to the other nu-cleotides. Nucleoside diphosphate kinase, found in all cells, catalyzes the reaction

Mg2+

Although this reaction is fully reversible, the relatively high [ATP]/[ADP] ratio in cells normally drives the reaction to the right, with the net formation of NTPs and dNTPs. The enzyme actually catalyzes a two-step phos-phoryl transfer, which is a classic case of a double-displacement (Ping-Pong) mechanism (Fig. 13-12; see also Fig. 6-13b). First, phosphoryl group transfer from ATP to an active-site His residue produces a phosphoenzyme intermediate; then the phosphoryl group is transferred from the (P)-His residue to an NDP acceptor. Because the enzyme is nonspecific for the base in the NDP and works equally well on dNDPs and NDPs, it can synthesize all NTPs and dNTPs, given the corresponding NDPs and a supply of ATP.

Phosphoryl group transfers from ATP result in an accumulation of ADP; for example, when muscle is contracting vigorously, ADP accumulates and interferes with ATP-dependent contraction. During periods of intense demand for ATP, the cell lowers the ADP concentration, and at the same time acquires ATP, by the action of adenylate kinase:

This reaction is fully reversible, so after the intense demand for ATP ends, the enzyme can recycle AMP by converting it to ADP, which can then be phosphorylated to ATP in mitochondria. A similar enzyme, guanylate ki-nase, converts GMP to GDP at the expense of ATP. By pathways such as these, energy conserved in the cata-bolic production of ATP is used to supply the cell with all required NTPs and dNTPs.

Phosphocreatine (Fig. 13-5), also called creatine phosphate, serves as a ready source of phosphoryl groups for the quick synthesis of ATP from ADP. The phosphocreatine (PCr) concentration in skeletal muscle is approximately 30 mm, nearly ten times the concentration of ATP, and in other tissues such as smooth muscle, brain, and kidney [PCr] is 5 to 10 mm. The enzyme creatine kinase catalyzes the reversible reaction

Mg2+

When a sudden demand for energy depletes ATP, the PCr reservoir is used to replenish ATP at a rate considerably faster than ATP can be synthesized by catabolic pathways. When the demand for energy slackens, ATP produced by catabolism is used to replenish the PCr reservoir by reversal of the creatine kinase reaction. Organisms in the lower phyla employ other PCr-like molecules (collectively called phosphagens) as phosphoryl reservoirs.

Ping

FIGURE 13-12 Ping-Pong mechanism of nucleoside diphosphate kinase. The enzyme binds its first substrate (ATP in our example), and a phosphoryl group is transferred to the side chain of a His residue. ADP departs, and another nucleoside (or deoxynucleoside) diphos phate replaces it, and this is converted to the corresponding triphosphate by transfer of the phosphoryl group from the phosphohistidine residue.

Inorganic Polyphosphate Is a Potential Phosphoryl Group Donor

Inorganic polyphosphate (polyP) is a linear polymer composed of many tens or hundreds of Pi residues linked through phosphoanhydride bonds. This polymer, present in all organisms, may accumulate to high levels in some cells. In yeast, for example, the amount of polyP that accumulates in the vacuoles would represent, if distributed uniformly throughout the cell, a concentration of 200 mM! (Compare this with the concentrations of other phosphoryl donors listed in Table 13-5.)

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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