Alkaline phosphatase in pregnancy

C18. Coryn, G., Elevation of seriun alkaline phosphatase in pregnancy. J. Chir. (Paris) 33, 213 (1934). 

L9. Leroux, M., and Perry, W. F., Serum heat-stable alkaline phosphatase in pregnancy. 

R26. Romslo, I., Sagen, N., and Haram, K., Serum alkaline phosphatase in pregnancy. Acta Obstet. Gynecol. Scand. 54, 437-442 (1975). 

Z4. Zuckerman, H., Sadovsky, E., and Kallner, B., Serum alkaline phosphatase in pregnancy and puerperium. Obstet. Gynecol. 25, 819-824 (1965). 

Historically, bile salts were first (B29) found to inhibit bone but not intestinal alkaline phosphatase, a fact that suggested organ differences in this enzyme. Somewhat later, the serum alkaline phosphatase of pregnancy was found to be similarly insensitive to bile salts. 

The resolution of the isozymes of human alkaline phosphatase in normal individuals by starch-gel electrophoresis was systematically studied in 1961 by Boyer, who observed a characteristic alkaline phosphatase pattern similar in pregnancy sera and in placenta (B38). With regard to placenta, recent work (H5, R15, R16) has indicated genetic variation of placental alkaline phosphatase in human placenta when the starch-gel electrophoresis is carried out at two different pH s (8.6 and 6.0). Other tissues could not be differentiated by their starch-gel patterns by Boyer (B38, B39). 

French workers (C4, CIS) discovered in 1934 that pregnancy serum exhibits elevations in alkaline phosphatase. The origin of the enzyme has been attributed variously to maternal osteoblastic activity, to fetal osteoblastic activity, and to placenta. Following Boyer s electrophoretic studies (B38), which showed that serum exhibits a strong enzyme band in the placental region, and Posen s demonstration of heat-stable placenta-type alkaline phosphatase in serum (C13), the reasonable view now is that the placenta supplies alkaline phosphatase to the circulation. 

Donayre and Pincus have studied serum alkaline phosphatase in the menstrual cycle (D19), and Climie et al. (Cll) have related neutrophile alkaline phosphatase and pregnancy. 

With the aid of photomicrographs of the L-phenylalanine-sensitive placental alkaline phosphatase, one can picture the placental villi in contact with the maternal circulation (H3) and so enriching it with alkaline phosphatase. In support of this view, we have demonstrated a progressive rise in pregnancy of heat-stable LPSAP with an optimum pH of 10.7. 

Fig. 4. Serum alkaline phosphatase in 31 healthy women during the second and third trimesters of pregnancy. The continuous line represents the mean and the shaded area, the 2.5-97.5 percentiles. (A) represents total alkaline phosphatase and (B) the placental fraction. Most of the increase is due to the placental enzyme. From Romslo et al. (R26) with permis-...

DeCarli et al., 1963). Also, hormone induction of alkaline phosphatase in HeLa cell cultures has been extensively studied (GriflFen and Cox, 1966 Melnykovych et al., 1967) with attention to chromosomal number (GriflFen and Bottomley, 1969). In the area of development, the diflFer-entiation of alkaline phosphatase has been evaluated (Moog et al., 1969) and in pregnancy, interesting work in the rat (Manning et al., 1969) and in the human (Posen et al., 1969 Fishman et al., 1972) have been conducted. Biochemical work has centered on the role of zinc (Simpson and... 

Whyte MP, Landt M, Ryan LM, Mulivor RA, Henthorn PS, Fedde KN, Mahuren JD, Coburn SP. 1995. Alkaline phosphatase placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5 -phosphate. Substrate accumulation in carriers of hypophos-phatasia corrects during pregnancy. J Clin Invest 95 1440-5. 

However, other isoenzymes of alkaline phosphatase are found in parts of the body such as bone, kidney, intestine and placenta, hence an isolated raised alkaline phosphatase may not be associated with liver dysfunction. In late pregnancy, alkaline phosphatase can increase to three times ULN, which may persist for several months after delivery, particularly if the mother is breastfeeding, owing to bone effects. In... 

Diagnosis of renal problems, xanthinuria, and toxemia of pregnancy via determination of the ratio of hypoxanthine to xanthine in plasma is facilitated by the use of biosensors. Xanthine oxidase immobilized on aminopropyl-CPG (controlled pore glass) activated with glutaraldehyde oxidizes hypoxanthine first to xanthine and then to uric acid. Use of an IMER with biosensors for hypoxanthine, xanthine, and uric acid provides the necessary data. Pre- or postcolumn enzymatic reactions catalyzed by creatinine deiminase, urease, alkaline phosphatase, ATPase, inorganic pyrophosphatase, or arylsufatase facilitate analysis of uremic toxins (simultaneous detection of electrolytes, serum urea, uric acid, creatinine, and methylguanidine). 

By contrast, the placental enzyme is distinguished by great heat stability, its activity unchanged after 30 minutes at 70°C in the presence of Mg +, according to Neale et al. (N18). It is noteworthy that pregnancy serum, especially in the third trimester, possesses a preponderance of heat-stable alkaline phosphatase (M15, N18). 

Human leukocytes possess alkaline phosphatase (L13, 03, RIO, T6, V3, V4) whose activity parallels the concentration of certain circulating steroids. Thus, during the menstrual cycle, the leukocyte alkaline phosphatase evidences a peak at midcycle corresponding to the higher estrogen level. In the later stages of pregnancy the enzyme level increases. Corti-coid hormones also exert an effect on leukocyte alkaline phosphatase. 

This section has been organized around the findings in the normal followed by examination of the same type of information in disease. The following and last section of this chapter concerns clinical entities (pregnancy and disease) in which the current status of our understanding of the significance of the serum alkaline phosphatase is described, as well as the inferences which may now be permitted from the foregoing biochemical approach. 

In general, it would seem that osteoblasts could not compare as a source of alkaline phosphatase with intestine or placenta. In pregnancy the level of alkaline phosphatase is rarely increased above 10 Bodansky or Shinowara units, and yet the placenta s microvilli, which are extremely rich in alkaline phosphatase, are directly immersed in the ample and efficient maternal blood supply (H3). In the nonpregnant individual, therefore, before hyperphosphatasemia can be attributed to bone it would appear necessary to evaluate the intestinal contribution that is evident as heat-sensitive non-LPSAP protein. 

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