Serum Alkaline Phosphatase Activity As A Potential Biomarker For The Intergrity Of The Hepatic Drainage System In Acute Falciparum Malaria Infection
I Garba, U Gregory
blood, disease, enzyme, liver, malaria, phosphatase
I Garba, U Gregory. Serum Alkaline Phosphatase Activity As A Potential Biomarker For The Intergrity Of The Hepatic Drainage System In Acute Falciparum Malaria Infection. The Internet Journal of Infectious Diseases. 2004 Volume 4 Number 2.
Alkaline Phosphatase (Orthophosphoric monoester phosphohydrolase, alkaline optimum (E.C. 18.104.22.168)) is an enzyme which catalyses the hydrolysis of a number of phosphate esters, transferring the phosphate group to an acceptor molecule. The pH optimum for the reaction is in the alkaline range, around 10. Alkaline phosphatase is a membrane-bound metalloenzyme comprising a group of isoenzymes encoded by at least four different gene loci 1. They are: tissue-specific, placental, intestinal and germ cell alkaline phosphatase. Each isoform of this enzyme has a slightly different pH optimum as well as different substrate preferences and concentration for maximum activity2. The two major and clinically most relevant isoenzymes in human serum are bone and liver alkaline phosphatase formed through post-translational modifications of the tissue non-specific gene product 3. They mainly circulate in soluble dimeric forms. Several theories have been postulated with respect to the biochemical role of alkaline phosphatase isoenzymes4. The liver fraction is believed to be involved in the transport processes. The bone isoenzyme is thought to enhance bone formation via enzymic hydrolysis of orthophosphate, an inhibitor of calcium deposition 5. The intestinal fraction is thought to be involved in some manner with metabolite transport across cell membranes 6 and calcium absorption 3. Phosphate absorption is believed to be facilitated by both intestinal and kidney isoenzymes. All fractions show some ability to regulate the synthesis of DNA. No specific function has yet been suggested for the placental fraction, although some studies suggest it is part of the process of the nutrient transport to the fetus 7. Alkaline phosphatase is located in a wide variety of tissues. Significant amounts of the enzyme are found in the liver, placenta, intestine, kidney, bone and platelets in decreasing order 8. The primary clinical utility of alkaline phosphatase is in cases of suspected bone disorders and obstructive liver diseases. Raised serum levels are seen in different bone disorders including Paget's disease, osteomalacia, rickets, hyperparathyroidism, osteogenic sarcoma, fractures and osteoblastic metastases. Increased serum levels are also seen in liver disease associated with extra or intra-hepatic obstruction, obstructive jaundice, diabetes 9 infectious mononucleosis 10 biliary cirrhosis and cholestasis. Low serum levels are associated with protein-energy malnutrition, cardiac surgery, low dietary magnesium, hypothyroidism, pernicious anemia 11, hypervitaminosis D, scurvy, achondroplasia in children and estrogen replacement therapy in post-menopausal women with osteoporosis 12. In this work, we assayed for serum activity of alkaline phosphatase in adult patients with acute falciparum malaria infection. The location of this enzyme on the membrane of the hepatic drainage system 13 makes it a potentially important biomarker for the assessment of the integrity of this system during malaria infection.
Patients And Methods
A. World Medical Association's Declaration of Helsinki 20. B. APA Ethical Principles in the Conduct of Research With Human Participants 21. C. World Medical Association's Declaration of Lisbon on the Rights of the Patient 22. D. CIOMS / WHO International Guidelines for the Conduct of Research Involving Human Subjects 23.
The results are shown in tables 1 and 2 below.
Alkaline phosphatase activity in infected males was 5.85 ± 0.36 IU/L. This activity was found to differ significantly from the control alkaline phosphatase activity of 4.83 ± 0.35 IU/L in normal, healthy males, as shown in table 1, p = 0.001. The picture is similar in females. A significant increase was found in the serum activity of alkaline phosphatase in infected females. The mean serum alkaline phosphatase activity was found to be 6.35 ± 0.39 IU/L in infected females and 4.33 ± 0.23 IU/L in normal, healthy females, p = 0.003, table 1. Serum alkaline phosphatase level was also found to be lower in infected males (5.85 ± 0.36 IU/L) relative to their female counterparts (6.35 ± 0.39 IU/L) p > 0.05, table 2. Among the controls, alkaline phosphatase activity was not found to differ significantly between the males and the females p > 0.05.
In terms of pathogenesis, the host liver is among the organs affected in the early stage of