Intracellular Phosphate Turnover on Bioenergetics

In all cells, most of the major energy changes and re­action couplings involve nucleotides. Although the cell draws on a number of different nucleotide pools,

ATP → ADP + phosphate

Exchanges are the most common. Other exchanges, such as

ATP → AMP + pyrophosphate

OTP → CDP + phosphate

Occur, for example, during lipid metabolism, as do reactions. Uridine triphosphate (UTP) is utilized in polysacharide synthesis and guanosine triphosphate (GTP) is consumed during protein synthesis. The de- oxy derivatives of the nucleotides, dATP, dGTP, dUTP, and dCTP, are used during DNA synthesis.

Regeneration of the nucleoside triphosphates is cat­alyzed by a relatively nonspecific nucleoside diphos­phate kinase,

CTP + ADP →CTP + ADP

UDP + ATP → UTP + ADP

GTP + ADP → GTP + ADP

dCDP + ATP → dCTP + ADP

dADP + GTP →dATP + GDP

The total concentration of all nucleotides in cells that are metabolizing in a steady state is relatively constant and most of the adenylate is present in the form of ATP. When cellular activity increases, the level of ATP decreases and the combined level of ADP + AMP increases.

The changes that take place in the levels of these compounds cause an increase in re­action sequences such as those of glycolysis. Which generate ATP Conversely, when cellular activity decreases, the transient rise in ATP acts to slow down the ATP-generating systems. The regula­tion of ATP synthesis is achieved through feedback control of allosteric en­zymes by ATP, ADP, and AMP.

Although ATP hydrolysis is a major source of free energy in cells, cells do not form substantial reser­voirs of ATP. The amount of ATP present in a cell lasts for only a short time during periods of increased cellu­lar activity. Most cells contain additional reservoirs of compounds that can quickly be consumed to generate additional ATP. For example, striated muscle, smooth muscle, and nerve cells contain reservoirs of phosphocreatine. When the ATP levels in these cells undergo a marked decline, the enzyme creatine kinase is acti­vated and catalyzes the reaction

Phosphocreatine + ADP → creatine + ATP (AG⁰‘ = – 12.6 kJ/mole)

Phosphoarginine and polymetaphosphate play a simi­lar role in invertebrate and bacterial cells, respectively.