The Demand for ATP

Details of the mechanisms of repression of nitrogenase synthesis by dioxygen or fixed nitrogen involved genetical research and are outined later in this article. 

---

Sophorolipid is a glycolipid, ie it is composed of carbohydrate and lipid. It therefore contains moieties of widely different oxidation levels and its synthesis from single demand carbon sources has a high ATP demand. However, the demand for ATP is reduced if a mixture of glucose and C-18 alkane is used. If glucose and fatty add is used the ATP demand is reduced further and relatively high spedfic production rates can be achieved. 

The control of the rate of ATP synthesis is shared by several processes including the demand for ATP, the rate of ADP/ATP exchange, the activities of the enzymes... 

When a human muscle, which comprises exclusively anaerobic (i.e. type II6) fibres is physically active, glycogen conversion to lactate generates all the ATP that is required to support the activity. Type I or Ila fibres use this process only when the demand for ATP exceeds that which can be generated from aerobic metabolism, e.g. during hypoxia. The significance of fhese processes for generation of ATP by muscle during various athletic events is discussed in Chapter 13. 

Blood-bome fuels are glucose, which is derived from liver glycogen, and fatty acids derived from adipose tissue. Uptake depends on the flow of blood through the muscle, the concentration of the fuel in the blood and the demand for ATP within the muscle. During sustained exercise the flow of blood to the muscle can increase up to 50-fold and the rate of utilisation of the fuel can increase to a similar extent, yet the concentration of the fuels in blood remains remarkably constant (Table 13.5). 

Inhibition or failure to activate any one of these factors could result in fatigue. The primary change within a muscle fibre that results in fatigue is a decrease in the ATP/ADP concentration ratio. This arises when the demand for ATP by physical activity exceeds the ability of the biochemical processes within the fibre to generate ATP at a sufficient rate to satisfy this demand. The raison d etre for fatigue is to restrict the extent of the physical activity so that the ATP/TYDP ratio does not fall to such low values that sufficient energy cannot be transferred to power processes that are essential to the life of the cell (e.g. maintenance of the ion balance within the cell). Two key questions arise ... 

Uncouplers of Oxidative Phosphorylation In normal mitochondria the rate of electron transfer is tightly coupled to the demand for ATP. When the rate of use of ATP is relatively low, the rate of electron transfer is low when demand for ATP increases, electron-transfer rate increases. Under these conditions of tight coupling, the number of ATP molecules produced per atom of oxygen consumed when NADH is the electron donor—the P/O ratio-is about 2.5. 

Creatine functions as a phosphagen in muscle. Neither the small amount of ATP in muscle nor the speed with which metabolic activity can be increased, and hence ADP be rephosphorylated, matches the demand for ATP for rapid or sustained muscle contraction. Muscle contains a relatively large amount... 

Fatty acid oxidation is regulated by the mechanisms that control oxidative phosphorylation—by the demand for ATP. 

The TCA cycle occurs in the mitochondrion, where its flux is tightly coordinated with the rate of the electron transport chain and oxidative phosphorylation through feedback regulation that reflects the demand for ATP. The rate of the TCA cycle is increased when ATP utilization in the cell is increased through the response of several enzymes to ADP levels, the NADH/ NAD ratio, the rate of FAD(2H) oxidation or the Ccf concentration. For example, isocitrate dehydrogenase is allosterically activated by ADP. 

Using the simple rules of the system, it is easy to deduce that a lack of work equates with a decrease in ATP consumption that causes a slowing or even stopping of the oxidation of fuels by a cell. The driving force for the oxidation of fuels comes from the demand for ATP. It is not the supply of fuel but the demand for energy that determines if fuels are oxidized. 

The demand for ATP in the red blood cell appears to control the flux via glycolysis. ATP consumption by Na, K-ATPase is at a rate of -3 mmol [L cells] h. Since this ATP turnover constitutes -40% of the total turnover (Prob. 11.48) and knowing the volume of one red blood cell to be 86 fL, we can compute the number to be -30. 

In the initial stages of light exercise, therefore, the demand for ATP is met by the full oxidation of glucose through the Krebs cycle. 

It may seem logical that a rise in fatty acid availability will cause an increase in the rate of fatty acid oxidation. However, the rate of oxidation of fuel is matched purely to the demand for ATP and if glucose oxidation provides sufficient ATP, the extra supply of fatty acids is not metabolized. Fatty acid oxidation can be regulated by controlling the rate at which the fatty acids enter the mitochondria, and this, in turn, is dependent on the activity of carnitine acyl transferase I. This transferase is inhibited by malonyl CoA, the production of which (by acetyl-CoA carboxylase) is stimulated by insulin. So, under conditions of hypo-insulinemia, malonyl-CoA concentrations fall and carnitine acyl transferase I is activated. This stimulates the uptake of fatty acids into the mitochondrial matrix and promotes P-oxidation. It is not so much the rise in fatty acids in the blood that stimulates P-oxidation, but the fall in insulin concentration. 

It was noted above that the small amount of ATP in the body turns over rapidly, and ADP is rapidly rephosphorylated to ATP However, neither the small amount of ATP in muscle nor the speed with which metabolic activity can be increased, and hence ADP can be rephosphorylated, matches the demand for ATP for rapid or sustained muscle contraction. Muscle contains about four times more creatine phosphate than ATP as shown in Figure 3.11, this acts as a reservoir or buffer to maintain a supply of ATP for muscle contraction until metabolic activity increases. Creatine phosphate is sometimes called a phosphagen because it can be used to rephosphorylate ADP to ADP. 

An example of sensitive regulation at a branch point may be provided by the pathways of fatty acid utilization and oxidation in tissues. An increase in the extracellular long-chain fatty acid concentration results in many mammalian tissues in an increase in the rate of fatty acid oxidation. This is considered to be important in providing an alternative fuel for the tissue when the carbohydrate stores of the body are being depleted. Nonetheless the rate of fatty acid oxidation should also be controlled by the tissue in response to the demand for ATP this could be produced by... 

---