Alkaline phosphatase (ALP)

Alkaline phosphatase (ALP, ALKP) is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation. As the name suggests, alkaline phosphatases are most effective in an alkaline environment. It is sometimes used synonymously as basic phosphatase.

In humans, alkaline phosphatase is present in all tissues throughout the entire body, but is particularly concentrated in liver, bile duct, kidney, bone, and the placenta. Humans and most other mammals contain the following alkaline phosphatase isozymes:

•        ALPI – intestinal

•        ALPL – tissue-nonspecific (liver/bone/kidney)

•        ALPP – placental (Regan isozyme)

Normal ALP levels in adults are approximately 20 to 140 IU/L, though levels are significantly higher in children and pregnant women. Blood tests should always be interpreted using the reference range from the laboratory that performed the test. High ALP levels can occur if the bile ducts are obstructed. Also, ALP increases if there is active bone formation occurring, as ALP is a byproduct of osteoblast activity (such as the case in Paget's disease of bone). Levels are also elevated in people with untreated Coeliac Disease. Reduced levels of ALP are less common than elevated levels.

Elevated levels

If it is unclear why alkaline phosphatase is elevated, isoenzyme studies using electrophoresis can confirm the source of the ALP. Heat stability also distinguishes bone and liver isoenzymes ("bone burns, liver lasts"). Placental alkaline phosphatase is elevated in seminomas and active form of Rickets.

Reduced levels

The following conditions or diseases may lead to reduced levels of alkaline phosphatase:

•        Hypophosphatasia, an autosomal recessive disease

•        Postmenopausal women receiving estrogen therapy because of osteoporosis

•        Men with recent heart surgery, malnutrition, magnesium deficiency, hypothyroidism, or severe anaemia

•        Children with achondroplasia and cretinism

•        Children after a severe episode of enteritis

•        Pernicious anaemia

•        Aplastic anaemia

•        Chronic myelogenous leukaemia

•        Wilson's disease

•        In addition, the following drugs have been demonstrated to reduce alkaline phosphatase:

•        Oral contraceptives

What does it mean if my alkaline phosphatase (ALP) is high?

It’s important to note that elevated levels of ALP can range in severity. While a very high ALP level often means you have liver damage or a bone disorder, mildly elevated levels can be caused by many different factors — not necessarily a medical condition that needs treatment. If you only have a mild elevation in your ALP levels, your healthcare provider will likely not have you undergo extensive evaluation. Instead, they’ll likely monitor your levels over time to make sure they don’t get worse.

High alkaline phosphatase (ALP) levels may indicate that there’s damage to your liver or that you have a type of bone disorder. Liver damage creates a different type of ALP than bone disorders do. If your test results reveal that you have high ALP levels, your provider may have you undergo additional tests, such as an ALP isoenzyme test, to determine where the excess ALP is coming from.

High alkaline phosphatase levels in the liver may indicate the following conditions:

Cholestasis of pregnancy: This is a common liver disease that can develop late in pregnancy.

Cirrhosis of the liver: Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged.

Hepatitis: Hepatitis is inflammation of the liver. There are many types of hepatitis.

Biliary atresia: This is a rare condition that happens when there’s a blockage in the tubes (ducts) that carry bile from your liver to your gallbladder. It occurs in infants.

Biliary stricture: This condition happens when the bile duct (the tube that takes bile from the liver to the small bowel) gets smaller or narrower.

Biliary obstruction due to cancer: Certain cancers, including cholangiocarcinoma and pancreatic head adenocarcinoma, can block your bile ducts or pancreatic ducts.

Mononucleosis (“mono”): This is a contagious infection that can sometimes cause swelling in your liver.

High bone alkaline phosphatase levels may indicate the following conditions:

Bone metastasis: This condition happens when cancer cells from elsewhere in your body spread to your bones.

Paget’s disease of the bone (osteitis derformans): This is a rare chronic bone disorder in which there is excessive breakdown and regrowth in the affected bone(s).

Osteogenic sarcoma: This is a type of cancer that starts in your bones.

Healing fractures.

Hyperparathyroidism: This condition happens when your parathyroid glands release too much parathyroid hormone, which causes calcium levels in your blood to rise.

Hyperthyroidism: This condition happens when your thyroid produces and releases too much thyroid hormone.

Osteomalacia: This is a disease that weakens your bones and can cause them to break more easily. It develops most commonly due to a vitamin D deficiency.

A high level of ALP may also be a sign of untreated celiac disease.

What does it mean if my alkaline phosphatase (ALP) is low?

Having an abnormally low level of alkaline phosphatase (ALP) is less common than having an elevated level. It may indicate the following conditions:

Malnutrition.

Zinc deficiency.

Magnesium deficiency.

Hypothyroidism.

Rare genetic conditions, including hypophosphatasia and Wilson disease.

1.       https://my.clevelandclinic.org/health/diagnostics/22029-alkaline-phosphatase-alp

2.       McComb RB, Bowers GN, Posen S. Alkaline phosphatase. New York: Plenum Publishing Corp; 1979.

3.       Tsai LC, Hung MW, Chen YH, Su WC, Chang GG, Chang TC. Expression and regulation of alkaline phosphatases in human breast cancer MCF-7 cells. Eur J Biochem. 2000;267:1330–1339. doi: 10.1046/j.1432-1327.2000.01100.x. - DOI - PubMed

4.       Chang TC, Wang JK, Hung MW, Chiao CH, Tsai LC, Chang GG. Regulation of the expression of alkaline phosphatase in a human breast cancer cell line. Biochem J. 1994;303:199–205. - PMC - PubMed

5.       Whyte MP, Landt M, Ryan LM, Mulivor RA, Henthorn PS, Fedde KN, Mahuren JD, Coburn SP. Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5′-phosphate substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. J Clin Invest. 1995;95:1440–1445. doi: 10.1172/JCI117814. - DOI - PMC - PubMed

6.       Calhau C, Martel F, Hipolito-Reis C, Azevedo I. Effect of P-glycoprotein modulators on alkaline phosphataseactivity in cultured rat hepatocytes. Cell Physiol Biochem. 2000;10:195–202. doi: 10.1159/000016350. - DOI - PubMed