Phosphorylases animal

BVdU is degraded by thymidine phosphorylase more rapidly than the natural substrate, thymidine. This rapid enzymic degradation may present a problem in its clinical use. Moreover, herpes vimses develop resistance to BVdU, apparendy because of mutant vimses that have lower thymidine kinase activity. G. D. Seade has dropped further development of BVdU because of increased animal tumor incidence induced by prolonged dosing (1). 

Experiments were also carried out injecting [3 -3H]xylosyl-MTA. The results indicated that the molecule has a very low turnover rate in D. verrucosa, since 96% of the recovered radioactivity after 24 h was associated with xylosyl-MTA. Accordingly, it was observed [126] that xylosyl-MTA is resistant to the enzyme MTA-phosphorylase which cleaves MTA but not the xylose analog, which therefore accumulates in the animal. Since xylosyl-MTA is mainly concentrated in the hermaphrodite gland of D. verrucosa and is very abundant in the eggmasses [103], it may play a role in the reproductive biology of D. verrucosa. 

Alkaline phosphatases [AP, orthophosphoric-monoester phosphorylase (alkaline optimum) EC 3.1.3.1] represent a large family of almost ubiquitous isoenzymes found in organisms from bacteria to animals. In mammals, there are two forms of AP, one form present in a variety of tissues and another form found only in the intestines. They share common attributes in that the phosphatase activity is optimal at pH 8-10, is activated by the presence of divalent cations, and is inhibited by cysteine, cyanides, arsenate, various metal chelators, and phosphate ions. Most conjugates created with AP utilize the form isolated from calf intestine. 

Since D-fructose and D-glucose phosphates are amongst the first products of photosynthesis, and since starch (in plants) and glycogen (in animals) are converted by phosphorylase to D-glucosyl phosphate, biosynthesis of carbohydrates revolves around these ubiquitous compounds... 

Glycogen and its enzymes are compartmentalized. Glycogen granules are only present in astrocytes of adult animals but are found in both astrocytes and neurons of immature animals. Of the enzymes involved in glycogen metabolism, glycogen phosphorylase is found in astrocytes only. Under steady-state conditions, it is probable that less than 10% of phosphorylase in brain is in the unphosphorylated b form (requiring AMP). This form is probably not very active at the low AMP concentrations present when intracellular glucose is sufficient to maintain ATP synthesis. Brain phosphorylase b kinase is activated indirectly by cAMP and by the molar concentrations... 

In a second class of regulatory enzymes the active and inactive forms are inter-converted by covalent modifications of their structures by enzymes. The classic example of this type of control is the use of glycogen phosphorylase from animal tissues to catalyse the breakdown of the polysaccharide glycogen yielding glucose-1-phosphate, as illustrated in Fig. 5.37. 

Figure 6.1 also includes the sequence comparison with the rabbit muscle phosphorylase.I6,30) The sequence homologies of the animal enzyme with the potato type-L and type-H phosphorylase isozymes are 38% and 47%, respectively. Further sequence comparison of the plant and animal enzymes with the enzyme from E. co/i82 reveals an overall homology of at least 40%. These high similarities indicate that the phosphorylase family is one of the well-conserved protein groups. 

In conclusion, it should be pointed out that in marked contrast to the very extensive studies on rabbit muscle phosphorylase, little attention has been paid to enzymes from other sources. However, primary structures of plant phosphorylases have now been determined and bacterial expression systems for the plant enzymes have also been made available as reviewed in this article. We hope that future studies on the structure and function of plant phosphorylases without allosteric regulation and comparison with those of the highly regulated animal enzyme will provide valuable information on this interesting group of enzymes, phosphorylases. 

Evidence for the presence of hyperglycemic factors in the CC were reported first in P. americana (1) and supported subsequently in B. discoidalis (3). The HGHs act on the fat body, the synthetic source for trehalose in insects (22), to elevate phosphorylase activity and the conversion of glycogen stores to the precursors for trehalose synthesis (2,3). Initially, it was believed that HGHs activated phosphorylase via the synthesis of adenosine 3 5 -cyclic monophosphate (cAMP) in the same manner that glucagon or epinephrine activate liver phosphorylase in vertebrate animals (23). Injections of intact adult P. americana with synthetic Pea-CAH-I and -II result in a 50% net increase in fat body cAMP over water-injected controls accompanied by a more than 3-fold increase in fat body phosphorylase activity (24). However, the CAHs fail to elevate cAMP levels of fat bodies from P. americana in vitro even though both phosphorylase activity and trehalose synthesis increase (25). In the latter case, Ca + is essential for the action of the CAHs, and its omission from the incubation medium inhibits the hypertrehalosemic response. 

The probable mode of action of the fluorides is the inhibition of a large number of metal-containing enzymes with which the fluoride forms complexes. These enzymes include phosphatases and phosphorylases. Because sodium fluoride may complex with many key enzymes, it is highly toxic to all plant and animal life. An example of a commercial product is Florocid. 

Phosphorylase is an enzyme of wide, if not universal, occurrence in plants. It is also found in animal skeletal muscle, liver, and heart. In animals, phosphorylases usually exist in two forms, the a form and the b form. The b form is converted enzymically into the active a form by phosphorylation. Phosphorylases isolated from different sources appear to differ in structure, but it is not yet known whether they differ in action pattern. 

Phosphorylase activity has been found in a large number of tissues and animal species. Muscle phosphorylase b is converted to phosphorylase a under the catalytic influence of phosphorylase kinase by a reaction requiring both Ca and Mg" Figure 6.3). Both forms of muscle phosphorylase require 5 -AMP, although the for phosphorylase a is so low that for physiological processes the assumption of independence is... 

Phosphorylases from animal, bacterial, and plant sources can be distinguished by their substrate preferences. Animal and bacterial phosphorylases prefer the short outer branches of highly branched cz-glucans, such as glycogen. The phosphorylase from Corynebacterium cal-luna, which accumulates a starch-like polysaccharide, is exceptional among bacterial enzymes... 

Purine nucleosides are cleaved by the action of purine nucleoside phosphorylase with the liberation of ribose 1-phosphate (Kl, PI). The enzyme is apparently specific for purines. The material from erythrocytes catalyzes the phosphorolysis of purine but not pyrimidine nucleosides (T6.) Purine phosphorylase activity is found widespread in nature and in many animal tissues (FIO). Friedkin and Kalckar investigated an enzyme capable of cleaving purine deoxynucleosides to the aglycone and deoxy-ribose 1-phosphate. They concluded that the enzyme was identical to that which splits purine ribonucleosides (F8, F9). This enzyme is capable of degrading inosine, xanthosine, and guanosine to forms readily attacked by other enzymes. In so doing, it permits living cells to retain the ribose and deoxyribose moieties. 

---