Alkaline phosphatase (ALP) is a homodimeric protein optimally active at alkaline pH.
It role is dephosphorylating compounds.
It plays an integral role in metabolism within the liver and development within the skeleton.
It is used by diagnosticians as a biomarker to determine diagnoses such as hepatitis or osteomalacia.
Its blood levels depend on factors such as age, gender, and blood type.
Blood levels increase two to four times during pregnancy, as a result of additional alkaline phosphatase produced by the placenta.
Abnormal levels could indicate issues relating to the liver, gall bladder or bones.
Abnormal levels may be seen in infections and kidney tumors.
Differential centrifugation of the blood to isolate leukocytes and staining can categorize each leukocyte into specific leukocyte alkaline phosphatase levels.
There are four sites of tissue expression: Intestinal, Placental, Germ Cell, and Liver/Bone/Kidney ALP.
The inorganic phosphates produced by these isozymes are then bound to carrier proteins which deliver the inorganic phosphates across the cytoplasmic membrane.
The main purpose of dephosphorylation by alkaline phosphatase is to increase the rate of diffusion of the molecules into the cells and inhibit them from diffusing out.
There is a positive correlation between serum bone alkaline phosphatase (B-ALP) levels and bone formation in humans.
AP affects the inflammatory responses in patients with chronic kidney disease and is directly associated with erythropoiesis stimulating agent resistant anemia.
It is present in all tissues throughout the entire body, but is particularly concentrated in the liver, bile duct, kidney, bone, intestinal mucosa and placenta.
In the serum, two types of alkaline phosphatase isozymes predominate: skeletal and liver.
During childhood the majority of alkaline phosphatase are of skeletal origin.
Humans and most other mammals contain the following alkaline phosphatase isozymes:
ALPI – intestinal
ALPL – tissue-nonspecific
ALPP – placental
GCAP – germ cell
Four genes encode the four isozymes.
The gene for tissue-nonspecific alkaline phosphatase is located on chromosome 1.
The genes for the other three isoforms are located on chromosome 2.
Intestinal alkaline phosphatase is secreted by enterocytes, and has a role in intestinal homeostasis and protection as well as in mediation of inflammation.
It represses the inflammatory cascade in the bowel, and regulates lipid absorption and bicarbonate secretion in the duodenal mucosa, which regulates the surface pH.
Significantly higher levels occur in children and pregnant women.
High ALP levels can occur if the bile ducts are obstructed.
It increases if there is active bone formation occurring, as ALP is a byproduct of osteoblast activity.
Levels are also elevated in people with untreated coeliac disease.
The concomitant increase of ALP with GGT should raise the suspicion of hepatobiliary disease.
Hepatitis C. does not affect the levels of alkaline phosphatase.
Elevated alkaline phosphatase seen in:
Biliary obstruction
Bone conditions
Osteoblastic bone tumors
Osteomalacia
Osteoporosis
Hepatitis
Cirrhosis
Myelofibrosis
Leukemoid reaction
Lymphoma
Paget’s disease
Sarcoidosis
Hyperthyroidism
Hyperparathyroidism
Myocardial infarction
Pregnancy
Reduced levels of alkaline phosphatase may be associated with:
Hypophosphatasia
Postmenopausal women receiving estrogen therapy because of aging.
Men with recent heart surgery, malnutrition, magnesium deficiency, or severe anemia.
Children with achondroplasia and cretinism.
Children after enteritis
Pernicious anemia
Aplastic anemia
Wilson’s disease
Hypothyroidism
Oral contraceptives
Levels along with prostate specific antigen during, and after six months of hormone treated metastatic prostate cancer was shown to predict the survival of patients.
Leukocyte alkaline phosphatase (LAP) is found within mature white blood cells.
Leukocyte alkaline phosphatase elevated levels are seen in the physiological response, the leukemoid reaction, and in pathologies that include mature white blood cells, such as polycythemia vera (PV), essential thrombocytosis (ET), and in primary myelofibrosis (PM).
Lower levels are found in pathologies that involve undeveloped leukocytes, such as chronic myelogenous leukemia[65] (CML), paroxysmal nocturnal hemoglobinuria (PNH) and acute myelogenous leukaemia (AML).