Adenosine triphosphates

Coenzymes effecting transfer of groups. Examples of this class are adenosine triphosphate (ATP), biotin, coenzyme A and pyridoxal phosphate. 

Calculation of Conformational Free Energies for a Model of a Bilobal Enzyme Protein kinases catalyze the transfer of phosphate from adenosine triphosphate (ATP) to protein substrates and are regulatory elements of most known pathways of signal transduction. 

A naturally occurring sulfonium salt S adenosylmethionme (SAM) is a key sub stance in certain biological processes It is formed by a nucleophilic substitution m which the sulfur atom of methionine attacks the primary carbon of adenosine triphosphate dis placing the triphosphate leaving group as shown m Figure 16 7... 

Adenosine triphosphate (ATP) is a key compound m biological energy storage and delivery... 

Glucose [50-99-7] urea [57-13-6] (qv), and cholesterol [57-88-5] (see Steroids) are the substrates most frequentiy measured, although there are many more substrates or metaboUtes that are determined in clinical laboratories using enzymes. Co-enzymes such as adenosine triphosphate [56-65-5] (ATP) and nicotinamide adenine dinucleotide [53-84-9] in its oxidized (NAD" ) or reduced (NADH) [58-68-4] form can be considered substrates. Enzymatic analysis is covered in detail elsewhere (9). 

Phosphorus. Eighty-five percent of the phosphoms, the second most abundant element in the human body, is located in bones and teeth (24,35). Whereas there is constant exchange of calcium and phosphoms between bones and blood, there is very Httle turnover in teeth (25). The Ca P ratio in bones is constant at about 2 1. Every tissue and cell contains phosphoms, generally as a salt or ester of mono-, di-, or tribasic phosphoric acid, as phosphoHpids, or as phosphorylated sugars (24). Phosphoms is involved in a large number and wide variety of metaboHc functions. Examples are carbohydrate metaboHsm (36,37), adenosine triphosphate (ATP) from fatty acid metaboHsm (38), and oxidative phosphorylation (36,39). Common food sources rich in phosphoms are Hsted in Table 5 (see also Phosphorus compounds). 

Active Transport. Maintenance of the appropriate concentrations of K" and Na" in the intra- and extracellular fluids involves active transport, ie, a process requiring energy (53). Sodium ion in the extracellular fluid (0.136—0.145 AfNa" ) diffuses passively and continuously into the intracellular fluid (<0.01 M Na" ) and must be removed. This sodium ion is pumped from the intracellular to the extracellular fluid, while K" is pumped from the extracellular (ca 0.004 M K" ) to the intracellular fluid (ca 0.14 M K" ) (53—55). The energy for these processes is provided by hydrolysis of adenosine triphosphate (ATP) and requires the enzyme Na" -K" ATPase, a membrane-bound enzyme which is widely distributed in the body. In some cells, eg, brain and kidney, 60—70 wt % of the ATP is used to maintain the required Na" -K" distribution. 

Molybdate is also known as an inhibitor of the important enzyme ATP sulfurylase where ATP is adenosine triphosphate, which activates sulfate for participation in biosynthetic pathways (56). The tetrahedral molybdate dianion, MoO , substitutes for the tetrahedral sulfate dianion, SO , and leads to futile cycling of the enzyme and total inhibition of sulfate activation. Molybdate is also a co-effector in the receptor for steroids (qv) in mammalian systems, a biochemical finding that may also have physiological implications (57). 

Adenosine Triphosphate. Adenosine triphosphate [56-65-5] (ATP), hke adenosine, is an important intracellular... 

Table 3. Agonists and Antagonists of Adenosine Triphosphate and Receptors...

Pig. 2. Proposed mechanism of inbition of smooth muscle contraction by P2" gonists, where AMP is adenosine monophosphate, cAMP is cycHc-3 5 adenosine monophosphate, ATP is adenosine triphosphate, and -P is an attached phosphate. 

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

Adenosine is not active orally, but adrninistered as an iv bolus dmg adenosine rapidly eliminates supraventricular tachycardias within 1—2 min after dosing. The dmg slows conduction through the AV node. Adenosine is rapidly removed from the circulation by uptake into red blood ceUs and vascular endothehal ceUs. Thus the plasma half-life is less than 10 s. Adenosine is rapidly metabolized to inosine or adenosine monophosphate and becomes part of the body pool for synthesis of adenosine-triphosphate. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

A good example of an affinity label for creatine kinase has been presented (35). This enzyme catalyzes the reversible transfer of a phosphoryl group from adenosine triphosphate [56-65-5] (17) to creatine [57-00-1] (18), leading to adenosine diphosphate [7584-99-8] (19) and phosphocreatine [67-07-2]... 

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