1. Adenylate Energy Charge Some enzymes respond to absolute concentration, but most respond to ratios. Dan Atkinson introduced the concept of ENERGY CHARGE in 1968 to summarize the energy status of a cell. It is a measure of the relative concentration of high-energy phospho - anhydride bonds available in the adenylate pool. It is a measure of the relative concentration of high-energy phospho - anhydride bonds available in the adenylate pool.

3. The adenylate energy charge, or AEC, has the range 0 to 1.0. If all the adenylate is in the form of ATP, AEC = 1.0, and the potential for phosphoryl transfer is maximal. The adenylate energy charge, or AEC, has the range 0 to 1.0. If all the adenylate is in the form of ATP, AEC = 1.0, and the potential for phosphoryl transfer is maximal. At the other extreme, if AMP is the only adenylate form present, AEC = 0. At the other extreme, if AMP is the only adenylate form present, AEC = 0. Then the relative amounts of the three adenine nucleotides are fixed by the energy charge. The following figure shows the relative changes in the concentrations of the adenylates as energy charge varies from 0 to 1.0.

7. Regulatory enzymes in energy-producing catabolic pathways show greater activity at low energy charge, but the activity falls off sharbly as AEC approaches 1.0. In contrast, regulatory enzymes of anabolic sequences are not very active at low energy charge, but their activities increase as AEC nears 1.0. These contrasting responses are termed R, for ATP-regenerating, and U, for ATP-utilizing.

8. Regulatory enzymes such as PFK and pyrvuate kinase in glycolysis follow the R response curve as AEC is varied. Note that PFK itself is an ATP-utilizing enzyme, using ATP to phosphorylate fructose- 6-phosphate to yield fructose-1,6- bisphosphate. Nevertheless, because PFK acts physiologically as the valve controlling the flux of carbohydrate down the catabolic pathways of cellular respiration that lead to ATP regeneration, it responds as an “R” enzyme to energy charge.

9. Regulatory enzymes in anabolic pathways, such as acetyl-CoA carboxylase, which initiates fatty acid biosynthesis, respond as “U” enzymes. Regulatory enzymes in anabolic pathways, such as acetyl-CoA carboxylase, which initiates fatty acid biosynthesis, respond as “U” enzymes.

10. Cellular energy homoeostasis: maintenance of energy state by creatine kinase (CK) and adenylate kinase (AK) isoenzymes A fundamental principle in multicellular organisms is the strict maintenance of stable concentrations of intracellular oxygen and ATP as the universal energy currency of biological systems, as well as the tight regulation of energy utilization with energy supply.

11. Upon activation of excitable cells, such as skeletal and cardiac muscle, or brain and nerve cells, ATP turnover rates may increase by several orders of magnitude within seconds, but [ATP] remains remarkably stable and ATP/ADP ratios, as well as ATP/AMP ratios, are maintained as high as possible to guarantee optimal efficiency for cellular ATPases that are at work to perform a multitude of energy- dependent cellular activities, such as muscle contraction, cell motility and ion pumping.

12. concerted action of kinases involved in energy homoeostasis

13. ATP homoeostasis and maintenance of high ATP/ADP and ATP/AMP ratios are facilitated by the action of two well-known enzyme systems, working as very fast and efficient energy safeguards. First, CKs, efficiently regenerating ATP at the expense of phosphocreatine (PCr) by the following reaction. PCr+ADP ATP+Cr PCr+ADP ATP+Cr

15. Second, Adenylate kinase (AK), reconverting two ADP molecules into one ATP and one AMP. These two enzymes, working together in an subcellular energy distribution network or circuit temporally and, due to their subcellular microcompartmentation, to buffer subcellular ATP level. These two enzymes, working together in an subcellular energy distribution network or circuit temporally and, due to their subcellular microcompartmentation, to buffer subcellular ATP level.

17. A common cause of many diseases, like cardiac insufficiency, cardiac hypertrophy as well as most of the neurodegenerative pathologies, is a generally lowered cellular PCr/ATP ratio, indicating a lowered energy state of cells and tissues. This is often accompanied by elevated calcium levels, leading to chronic calcium overload with its host of negative consequences on cell function and viability. This is often accompanied by elevated calcium levels, leading to chronic calcium overload with its host of negative consequences on cell function and viability.