Properties of the acid phosphatases of erythrocytes and of the human prostate gland

Abul-Fadl, M. A. M.; King, E. J.

doi:10.1042/bj0450051

Cited by 262 publications

(53 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The phosphate esters 4a and 4b must undergo a chemical or enzymatic bioconversion to release the parent drug in order to fulfill the prodrug criteria. In addition to red blood cells 27 alkaline phosphatases have been found in various human tissues; e.g., placenta, intestine, liver, bone, and kidney, 28 and they have been reported to be the responsible enzymes for the hydrolysis of phosphate esters. 16,29 The susceptibility of buparvaquone phosphate esters (4a,b) to enzymatic hydrolysis was studied in alkaline phosphatase enzyme solution (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone

et al. 2003

View full text Add to dashboard Cite

Water-soluble phosphate prodrugs of buparvaquone (1), containing a hydroxynaphthoquinone structure, were synthesized and evaluated in vitro for improved topical and oral drug delivery against cutaneous and visceral leishmaniasis. The successfull prodrug synthesis involved a strong base; e.g., sodium hydride. Buparvaquone-3-phosphate (4a) and 3-phosphonooxymethylbuparvaquone (4b) prodrugs possessed significantly higher aqueous solubilities (>3.5 mg/mL) than the parent drug (e0.03 µg/mL) over a pH range of 3.0-7.4. Moreover, 4a and 4b maintained adequate lipophilicity as indicated by distribution coefficients (log D) between 0.5 and 3.0 over this pH range. Both 4a and 4b were also shown to be substrates for alkaline phosphatase in vitro and thus are promising bioreversible prodrugs for the improved topical and oral bioavailability of 1. Buparvaquone and its prodrugs showed nanomolar or lowmicromolar ED 50 activity values against species that cause cutaneous leishmaniasis, e.g., L. major, L. amazonensis, L. aethiopica, L. mexicana, and L. panamensis and also L. donovani, which is the causative agent of visceral leishmaniasis. From these results, the human skin permeation of the prodrugs 4a and 4b were studied in vitro. While no buparvaquone permeated across post mortem skin in vitro during 72 h of experiments, both prodrugs 4a and 4b permeated readily through the skin. In addition, 4b easily released the parent drug in human skin homogenate and, therefore, is a promising prodrug candidate to deliver buparvaquone through the skin for the treatment of cutaneous leishmaniasis.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone

et al. 2003

View full text Add to dashboard Cite

show abstract

“…In these respects, it behaves like the enzyme in normal serum (18,19). Others have shown that L-tartrate inhibits acid phosphatase from prostate, liver and spleen, but not the normal serum enzyme (18).…”

Section: Discussionmentioning

confidence: 99%

Platelets as a Source of Serum Acid Nitrophenylphosphatase*

Zucker¹,

Borrelli²

1959

J. Clin. Invest.

View full text Add to dashboard Cite

Recent interest in serum enzyme activity in pathological conditions has led to renewed curiosity concerning the source of the enzymes present in serum under normal conditions. Since blood platelets contain acid phosphatase (1-8), it seemed possible that they might liberate this enzyme during blood coagulation. This possibility was investigated by comparing the acid phosphatase activity of serum prepared from platelet-rich and platelet-poor plasmas. Preliminary studies suggested that the platelets contribute virtually all of the activity of normal serum against 8-glycerophosphate at acid pH (9). The present investigation was carried out using p-nitrophenylphosphate as substrate. METHODSAcid phosphatase activity was measured using p-nitrophenylphosphate 1 as substrate (10-12). This method gave highly reproducible values; for example, nine out of 10 determinations on a sample of fresh serum were 0.39 FM per ml. per hour and the tenth was 0.41.The subjects were either healthy young adults or, in a few instances, patients with metastatic carcinoma of the prostate.2 To avoid the use of anticoagulants, native platelet-rich and platelet-poor plasmas were prepared by centrifugation of blood drawn in chilled siliconed syringes and cooled in an ice bath in siliconed tubes. Most of the red and white cells were sedimented by centrifuging for five to 10 minutes at about 1,000 rpm. Two ml. of the supernatant platelet-rich plasma was set aside in an ice bath and a platelet count taken. The remainder of the native blood and platelet-rich plasma was centrifuged in a multispeed attachment at about 10,000 rpm for 10 minutes to obtain platelet-poor plasma. About removed with an applicator stick at the end of incubation, and acid phosphatase activity was measured. These samples are designated as "serum from platelet-rich plasma" and "serum from platelet-poor plasma." The time course of acid phosphatase liberation was studied by placing 0.4 ml. of native platelet-rich plasma in each of a series of new glass tubes (rinsed with distilled water and oven-dried) at 370 C. and, at intervals, removing the platelets. In the samples which had not yet clotted, this was accomplished by brief high-speed centrifugation and the fibrin which formed subsequently in the platelet-poor plasma was removed with an applicator stick. In the samples which had clotted, the clot and entrapped platelets were removed together.To determine whether anticoagulants inhibited enzyme activity, one-fifth volume of 0.1 M sodium oxalate, 0.11 M sodium citrate, or 0.027 M (1 per cent) disodium ethylenediaminetetraacetate in saline (EDTA) was added to serum separated from native platelet-rich plasma or from whole blood. To study the effect of the anticoagulants on the color of nitrophenol, saline was used instead of serum. The activity of whole platelets was tested by comparing the acid phosphatase activity of platelet-rich and platelet-poor plasmas separated from blood in which clotting was prevented by the addition of one-ninth volume of anticoagulant. Other studies we...

show abstract

“…The Acid-phosphatase activity was assessed at pH 4-9 (citrate) by the method described by Bell & Siller (1962) (Mann, 1954). Human prostatic acid phosphatase shows properties towards certain inhibitory substances that distinguish it from acid phosphatases from other sources (see Abul-Fadl & King, 1949). The effects of Ca2+, Cu2+, Mg2+, F~, and dextrorotatory tartrate on the acid-phosphatase activity of cock seminal-plasma acid phosphatase have already been reported (Bell & Lake, 1960, 1962 The results of the boar analyses show that the bulk of the alkaline phos¬ phatase accompanies the first or spermatozoon-rich wave of ejaculation.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Phosphomonoesterase Activities in the Seminal Plasmas of the Domestic Cock, Turkey Tom, Boar, Bull, Buck Rabbit and of Man

Bell¹,

Lake²

1962

Reproduction

View full text Add to dashboard Cite

Summary. A comparison of the phosphomonoesterase activity, against 4-nitrophenyl phosphate, in the seminal plasma of the domestic cock, turkey torn, boar, bull, buck rabbit and of man has been made. The acid-phosphatase(s) activity at pH 4-9 was highest in man, the cock and turkey torn, and lowest in the boar and rabbit, with the bull inter¬ mediate. Alkaline-phosphatase activity was highest in the boar and rabbit, lowest in the cock, turkey torn and in man, with the bull again intermediate. It is possible that much of the alkaline phosphatase in the boar semen was derived from the epididymis or testis or both.Unlike that of the mammals, the acid phosphatase (s) of cock seminal plasma was unable to hydrolyse choline-O-phosphate and the enzyme (s) activity in seminal plasma was only slightly, if at all, inhibited by dextrorotatory tartrate. The significance of these findings has been briefly discussed.

show abstract

Properties of the acid phosphatases of erythrocytes and of the human prostate gland

Cited by 262 publications

References 9 publications

Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone

Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone

Platelets as a Source of Serum Acid Nitrophenylphosphatase*

A Comparison of Phosphomonoesterase Activities in the Seminal Plasmas of the Domestic Cock, Turkey Tom, Boar, Bull, Buck Rabbit and of Man

Contact Info

Product

Resources

About