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Alkaline phosphatase: causes of variations

ALP
 

WHAT IS ALKALINE PHOSPHATASE

Structure of alkaline phosphatase molecule and mechanism of action
Structure of alkaline phosphatase molecule and mechanism of action.By Boghog2

Alkaline phosphatase (ALP, ALKP) is an enzyme of the hydrolase class. It performs dephosphorylation, i.e. splitting a phosphate (PO43-) off from the molecules of various organic compounds. The ultimate goal of such a manipulation is to move substances across the cell membranes. This enzyme is the most active under alkaline Ph - 8,6-10,1, as it is reflected in the term.

Alkaline phosphatase belongs to the number of the most prevalent and universal enzymes.

ALP molecule is made up of two protein submolecules, each of which normally has three active nuclei. Zinc plays a key role in alkaline phosphatase operation. While each active nucleus contains only one atom of Zinc, it still is of the utmost importance as a coenzyme that catalyzes a reaction of dephosphorylation. Studies show that alkaline phosphatase loses its functions right after atoms of Zinc are removed from it. Likewise, Magnesium is also required for ALP to be fully functional.

ALKALINE PHOSPHATASE ISOENZYMES

Alkaline phosphatase is present throughout all tissues of the human's body. It comprises three subsets, which are called "isoenzymes":

  • tissue-nonspecific ALP — ALPL (produced in all of the tissues)
  • intestinal ALP — ALPI (produced in an inner lining of the intestine)
  • placental ALP — ALPP (produced in placenta)

Genetic code for these isoenzymes is not stored in the same genes and even the same chromosomes. Therefore they have different structure, while performing the same job.

Similarly, tissue-nonspecific ALP is subdivided into:

  • liver ALP — ALPL-1 (produced in the linings of bile ducts)
  • bone ALP — ALPL-2 (produced in a bone tissue)
  • kidney ALP — ALPL-3 (produced in the linings of urinary tract)

They are also often referred to as isoenzymes. Though, researchers consider the term "isoenzymes" as somewhat of a misnomer, since initially they are manufactured identical from the same gene, and only then undergo additional modifications. That's why the right term for them is "isoforms", not "isoenzymes".

But in practice these theoretical nuances don't matter that much. What's really important is that any difference in structure gives an opportunity to distinguish between ALPs, because in most cases it's a way to find out, which tissue or organ is responsible for high level of the enzyme in blood.

A source of liver alkaline phosphatase are inner linings of intrahepatic and extrahepatic bile ducts. Any obstruction of bile outflow in any pathology of the liver or extrahepatic bile ducts pathology contributes to excess ALP in blood.

Bone alkaline phosphatase is produced in the bone tissue by specific cells - 'osteoblasts' that are in charge of a formation of bones.

Alkaline phosphatase in serum of adults is, in the main, represented by liver and bone isoenzymes in approximately equal quantities. Other isoenzymes are present in minor amounts.

ALP (and the other enzymes) is usually measured in the units of activity instead of units of weight. That is an expression of operation rate of the enzyme in given volume under strictly standardized conditions.

DIAGNOSTIC USE OF ALKALINE PHOSPHATASE

Unfortunately, total alkaline phosphatase proved not to be a reliable diagnostic marker. Oftentimes, it falls outside a healthy range in a perfectly healthy person, and vice versa, it's normal when it obviously shouldn't be. Analysis of ALP isoenzymes provides more information.

NORMAL LEVEL OF ALKALINE PHOSPHATASE

Total ALP 20 -140 ME/L

* Normal ALP values may vary with equipment used for measurements at the lab.

PHYSIOLOGICAL CAUSES OF ELEVATED ALKALINE PHOSPHATASE LEVEL

Normal level of alkaline phosphatase in children and adolescents is 2-3 times higher than its normal level in adults. In this case there is high bone isoenzyme level that results from an active bone growth, and as it slows down, the level decreases.

In pregnant women, alkaline phosphatase increases 2-3 times in the 3rd trimester of pregnancy because of placental isoenzyme, this elevation is physiologically normal.

CAUSES OF HIGH LEVEL OF ALKALINE PHOSPHATASE:

  1. Diseases of liver and bile ducts (excess liver isoenzyme):
    • viral, drug-induced, toxic hepatitis
    • intrahepatic cholestasis (slowing/stopping of bile flow)
    • cirrhosis
    • fatty liver
    • liver tumors
    • cholelithiasis
    • tumors and other diseases of pancreas and duodenum accomponied with blockage of a common bile duct
  2. Drugs that induce cholestasis (excess liver isoenzyme):
    • oral contraceptives
    • some antibiotics (erythromycin, flucloxacillin)
    • anabolic steroids
  3. Bone conditions (excess bone isoenzyme):
    • healing fractures
    • vitamin D-dependent rickets
    • osteoporosis (reduced mineralisation of bone tissue)
    • bone tumors
    • Paget's disease
  4. Nonskeletal conditions and factors that induce systemic disorders of bone metabolism and mineralization (excess bone isoenzyme):
    • Hodgkin's disease
    • multiple myeloma
    • hyperparathyroidism (overactivity of the parathyroid glands that results in excess calcium in blood)
    • chronic kidney disease
    • antiepileptic drugs (AEDs)

Total alkaline phosphatase increases 2-3 times in bone conditions and 3-10 times in biliary obstruction.

Total blockage of a common bile duct (so-called obstructive jaundice) results in extremely high level of alkaline phosphatase because of liver isoenzyme.

CAUSES OF LOW LEVEL OF ALKALINE PHOSPHATASE

  • vitamin B6, B12, C deficiency
  • Zink and Magnesium deficiency
  • folic acid deficiency
  • low phosphorus
  • malnutrution
  • lack of proteins
  • excess consumption of vitamin D
  • hypothyroidism (reduction of thyroid function)
  • hypoparathyroidism (reduction of parathyroids function)