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Alkaline phosphatase
 
 
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Alkaline phosphatase (ALP) is a hydrolase
Hydrolase

In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:...
 enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 responsible for removing phosphate
Phosphate

A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
 groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation
Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes....
. As the name suggests, alkaline phosphatases are most effective in an alkaline environment.

acteria, alkaline phosphatase is located in the periplasmic space
Periplasmic space

The periplasmic space or periplasm is a space between the inner cytoplasmic membrane and external outer membrane of Gram-negative bacterium or the equivalent space between the cell membrane and cell wall in Gram-positive bacteria....
, external to the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
.






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Alkaline phosphatase (ALP) is a hydrolase
Hydrolase

In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:...
 enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 responsible for removing phosphate
Phosphate

A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
 groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation
Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes....
. As the name suggests, alkaline phosphatases are most effective in an alkaline environment.

Bacterial

In bacteria, alkaline phosphatase is located in the periplasmic space
Periplasmic space

The periplasmic space or periplasm is a space between the inner cytoplasmic membrane and external outer membrane of Gram-negative bacterium or the equivalent space between the cell membrane and cell wall in Gram-positive bacteria....
, external to the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
. Since this space is much more subject to environmental variation than the actual interior of the cell, bacterial alkaline phosphatase is comparatively resistant to inactivation, denaturation
Denaturation (biochemistry)

Denaturation is a process in which proteins or nucleic acids lose their structure by application of some external stress or compound for example, treatment of proteins with strong acids or bases, high concentrations of inorganic salts, organic compound solvents , or heat....
, and degradation
Degradation

Degradation may refer to;* Degradation , metal band from Chicago, IL USA* Biodegradation, the processes by which organic substances are broken down by living organisms...
, and also has a higher rate of activity. Although the actual purpose of the enzyme is still not fully understood, the simple hypothesis, that it is a means for the bacteria to generate free phosphate groups for uptake and use, is supported by the fact that alkaline phosphatase is usually only produced by the bacteria during phosphate starvation and not when phosphate is plentiful(citation needed). However, other possibilities exist; for instance, the presence of phosphate groups usually prevents organic molecules from passing through the membrane, therefore dephosphorylating them may be important for bacterial uptake of organic compounds in the wild. Some complexities of bacterial regulation
Regulation

Regulation refers to "controlling human or societal behaviour by rules or restrictions." Regulation can take many forms: law restrictions promulgated by a government authority, self-regulation, social regulation , co-regulation and market regulation....
 and metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
 suggest that other, more subtle, purposes for the enzyme may also play a role for the cell. In the laboratory
Laboratory

A laboratory is a facility that provides controlled conditions in which science research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories....
, however, mutant
Mutant

A mutant is an individual, organism, or new genetic character arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or Trait not found in the wild type....
 Escherichia coli
Escherichia coli

'Escherichia coli' , is a Gram negative bacterium that is commonly found in the lower gastrointestinal tract of warm-blooded animals. Most E....
 lacking alkaline phosphatase survive quite well, as do mutants unable to shut off alkaline phosphatase production.

Use in research

The most common alkaline phosphatases used in research are:
  • Bacterial alkaline phosphatase (BAP), from Escherichia coli
    Escherichia coli

    'Escherichia coli' , is a Gram negative bacterium that is commonly found in the lower gastrointestinal tract of warm-blooded animals. Most E....
     C4 cells
  • Shrimp alkaline phosphatase (SAP), from a species of Arctic shrimp
    Shrimp

    Shrimp are swimming, Decapoda crustaceans classified in the infraorder Caridea, found widely around the world in both fresh water and seawater. Adult shrimp are Filter feeder benthic animals living close to the bottom....
     (Pandalus borealis
    Pandalus borealis

    Pandalus borealis is a species of shrimp found in cold parts of the Atlantic Ocean and Pacific Oceans. Many different English language names are used, with little consensus ....
    )
  • Calf intestine alkaline phosphatase (CIAP), from calf
    Calf

    File:New Forest calf.jpgA calf is the young of various species of mammal. The term is most commonly used to refer to the young of cattle. The young of bison, camels, dolphins, elephants, giraffes, hippopotamuses, moose, rhinoceroses, whales, seals and yaks are also called calves....
     intestine
    Intestine

    In anatomy, the intestine is the segment of the Gastrointestinal tract extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine....
  • Placenta
    Placenta

    The placenta or afterbirth is a highly vascularized ephemeral organ present in Placentalia vertebrates that connects the developing fetal tissues to the uterine wall....
    l alkaline phosphatase (PALP) and its C terminally truncated version that lacks the last 24 amino acids (constituting the transmembrane domain) - the secreted alkaline phosphatase (SEAP)


Alkaline phosphatase has become a useful tool in molecular biology
Molecular biology

Molecular biology is the study of biology at a molecule level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry....
 laboratories, since DNA
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
 normally possesses phosphate groups on the 5'
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
 end. Removing these phosphates prevents the DNA from ligating
Ligation

Ligation may refer to:* The act of making a Ligature . In medicine, a ligature is a device, similar to a tourniquet, usually of thread or string, tied around a limb, blood vessel or similar to restrict blood flow....
 (the 5' end attaching to the 3'
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
 end), thereby keeping DNA molecules linear until the next step of the process for which they are being prepared; also, removal of the phosphate groups allows radiolabeling (replacement by radioactive phosphate groups) in order to measure the presence of the labeled DNA through further steps in the process or experiment. For these purposes, the alkaline phosphatase from shrimp is the most useful, as it is the easiest to inactivate once it has done its job.

Another important use of alkaline phosphatase is as a label for enzyme immunoassays.

One common use in the dairy industry is as a marker of pasteurisation in cows milk. This molecule is denatured by elevated temperatures found during pasteurisation, and can be tested for via colour change of a para-nitro-phenol phosphate substrate in a buffered solution (Aschaffenburg Mullen Test). Raw milk would typically produce a yellow colouration within a couple of minutes, whereas properly pasteurised milk should show no change. There are of course exceptions to this in the case of heat stable alkaline phophatases produced by some bacteria.

Inhibitors

All mammalian alkaline phosphatase isoenzymes except placenta
Placenta

The placenta or afterbirth is a highly vascularized ephemeral organ present in Placentalia vertebrates that connects the developing fetal tissues to the uterine wall....
l (PALP and SEAP) are inhibited by homoarginine and similarly all except the intestinal and placental ones are blocked by levamisole
Levamisole

Levamisole is an antibiotic belonging to a class of synthetic imidazothiazole derivatives. It was discovered at Janssen Pharmaceutica in 1966....
. Heating for ~2 hours at 65oC inactivated most isoenzymes except Placental isoforms (PALP and SEAP).

Human


Physiology

In humans, alkaline phosphatase is present in all tissues throughout the entire body, but is particularly concentrated in liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
, bile duct
Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine....
, kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
, bone
Bone

Bones are rigid organ that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red blood cell and white blood cells and store minerals....
, and the placenta
Placenta

The placenta or afterbirth is a highly vascularized ephemeral organ present in Placentalia vertebrates that connects the developing fetal tissues to the uterine wall....
. The optimal pH for the activity of the E. coli
Escherichia coli

'Escherichia coli' , is a Gram negative bacterium that is commonly found in the lower gastrointestinal tract of warm-blooded animals. Most E....
 enzyme is 8.0 while the bovine
Cattle

Cattle, colloquially referred to as cows, are domestication ungulates, a member of the subfamily Bovinae of the family Bovidae. They are raised as livestock for meat , dairy products , leather and as draft animals ....
 enzyme optimum pH is slightly higher at 8.5.

Diagnostic use

The normal range is 39-120. High ALP levels can show that the bile duct
Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine....
s are blocked. Levels are significantly higher in children and pregnant women.

Lowered levels of ALP are less common than elevated levels.

The following conditions can cause abnormal levels of ALP:

Elevated levels (hyperphosphatasemia)
If it is unclear why alkaline phosphatase is elevated, isoenzyme studies using electrophoresis
Electrophoresis

Electrophoresis is the best-known electrokinetic phenomena. It was discovered by Reuss in 1807. He observed that clay particles dispersed in water migrate under influence of an applied electric field....
 can confirm the source of the ALP. Heat stability also distinguishes bone and liver isoenzymes ("bone burns, liver lasts").

  • Liver
    Liver

    The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
     (Liver ALP):
    • Cholestasis
      Cholestasis

      In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. Bile formation is a secretory function of the liver....
      , cholecystitis
      Cholecystitis

      Cholecystitis is inflammation of the gall bladder....
      , cholangitis
      Cholangitis

      Cholangitis is inflammation of the bile duct. The most common cause is a bacterial infection, and the problem is then an ascending cholangitis. However, there are other types of cholangitis as well....
      , cirrhosis
      Cirrhosis

      Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver Tissue by fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
      , hepatitis
      Hepatitis

      Hepatitis implies injury to the liver characterized by the presence of inflammatory cell s in the Tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation" ....
      , fatty liver
      Fatty liver

      Fatty liver, also known as fatty liver disease , steatorrhoeic hepatosis, or steatosis hepatitis, is a reversible condition where large vacuoles of triglyceride fat accumulate in hepatocyte via the process of steatosis....
      , liver tumor, liver metastases, drug intoxication
      • N.B. concurrently elevated GGT (gamma glutamyl transpeptidase
        Gamma glutamyl transpeptidase

        Gamma-glutamyl transferase is primarily a liver enzyme which catalyzes the following chemical reaction:-peptide + an amino acid peptide + 5-L-glutamyl amino acid...
        ) helps rule in favor of liver metastasis (rather than bone, kidney, etc.) when assessing spread of cancer.
    • Drugs
      Medication

      A pharmaceutical drug, also referred to as medicine or medicament, can be loosely defined as any substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease....
      : e.g. verapamil
      Verapamil

      Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches....
      , carbamazepine
      Carbamazepine

      Carbamazepine is an anticonvulsant and mood stabilizer drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat Attention-deficit hyperactivity disorder, ADHD, schizophrenia, phantom limb syndrome, paroxysmal extreme pain disorder, and trigeminal neuralgia....
      , phenytoin
      Phenytoin

      Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage gated sodium channels....
      , erythromycin
      Erythromycin

      Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins....
      , allopurinol
      Allopurinol

      Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout....
      , ranitidine
      Ranitidine

      Ranitidine hydrochloride is a histamine H2-receptor antagonist that inhibits gastric acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease ....
  • Bone
    Bone

    Bones are rigid organ that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red blood cell and white blood cells and store minerals....
     disease (Bone ALP):
    • Paget's disease
      Paget's disease

      Sir James Paget, a prolific surgeon and pathologist, described several diseases, including:* Paget's disease of bone * Paget's disease of the breast...
      , osteosarcoma
      Osteosarcoma

      Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. There is a preference for the metaphysis region of tubular long bones....
      , bone metastases of prostatic cancer (High / very high ALP values)
    • Other bone metastases
    • Fractured bone
    • Multiple myeloma
      Multiple myeloma

      Multiple myeloma is a cancer of plasma cells. These immune system cells are formed in bone marrow, are numerous in lymphatics and produce antibody....
       (only when associated with fractures)
  • Skeletal involvement of other primary diseases:
    • Osteomalacia
      Osteomalacia

      Osteomalacia is the general term for the softening of the bones due to defective bone mineralization. Osteomalacia in children is known as rickets, and because of this, osteomalacia is often restricted to the milder, adult form of the disease....
      , rickets
      Rickets

      Rickets is a softening of bones in children potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries....
      , vitamin D deficiency, (Moderate rise)
    • Malignant tumors (ALP originating from tumor)
    • Renal disease (secondary hyperparathyroidism
      Hyperparathyroidism

      Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels....
      )
    • Primary hypothyroidism
      Hypothyroidism

      Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
  • Polycythemia vera
    Polycythemia vera

    Primary polycythemia, often called polycythemia vera , polycythemia rubra vera , or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow and occasionally in the kidneys....
  • Myelofibrosis
    Myelofibrosis

    Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, and primary myelofibrosis, is a disorder of the bone marrow, in which the marrow undergoes fibrosis - replacement by fibrous tissue ....
  • Leukemoid reaction
    Leukemoid reaction

    The term leukemoid reaction, also referred to as transient myeloproliferative disorder, describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection ....
     to infection
  • Women using hormonal contraception
    Hormonal contraception

    Hormonal contraception refers to birth control methods that act on the hormone system.Currently, all hormonal contraceptives are designed for use by women rather than men, though research on a male oral contraceptive has been underway for some time....
  • Pregnancy
    Pregnancy

    Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or Multiple birth....
  • Biliary obstruction
  • Transient hyperphosphatasaemia of infancy: benign
    Benign

    A benign tumor is a tumor that lacks all three of the malignant properties of a cancer. Thus, by definition, a benign tumor does not grow in an unlimited, aggressive manner, does not invade surrounding tissue , and does not metastasize....
    , often associated with infection


Lowered levels (hypophosphatasemia)
  • Hypophosphatasia
    Hypophosphatasia

    Hypophosphatasia is a rare inherited metabolic disorder of decreased tissue nonspecific alkaline phosphatase and defective bone mineralization....
    , an autosomal recessive disease
  • Postmenopausal
    Menopause

    The Menopause is the permanent cessation of menstruation which occurs a considerable length of time before the end of the lifespan.The word was first applied to humans, and because of this it literally means the cessation of monthly cycles or menstrual cycles, from the Greek roots meno and pausis ....
     women receiving estrogen therapy because of osteoporosis
    Osteoporosis

    Osteoporosis is a disease of bone that leads to an increased risk of bone fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of collagen proteins in bone is altered....
  • Men with recent heart surgery, malnutrition
    Malnutrition

    Malnutrition is a general term for a medical condition caused by an improper or inadequate diet and nutrition.According to the World Health Organization, hunger and malnutrition are the single gravest threats to the world's public health and malnutrition is by far the biggest contributor to child mortality, present in half of all cases....
    , magnesium
    Magnesium

    Magnesium is a chemical element with the symbol Mg, atomic number 12, atomic weight 24.3050 and common oxidation number +2.Magnesium, an alkaline earth metal, is the ninth most abundance of the chemical elements in the universe by mass....
     deficiency, hypothyroidism
    Hypothyroidism

    Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
     or severe anemia
    Anemia

    Anemia or an?mia/anaemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells ....
  • Children with achondroplasia
    Achondroplasia

    Achondroplasia dwarfism is a type of autosomal Dominance genetic disorder that is a common cause of dwarfism. Achondroplastic dwarfs have short stature, with an average adult height of 131 centimeter for males and 123 cm for females....
     and cretinism
    Cretinism

    Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital disorder deficiency of thyroid hormones or from prolonged nutritional deficiency of iodine....
  • Children after a severe enteritis
    Enteritis

    In medicine, enteritis refers to inflammation of the small intestine. See also inflammation of related organs of the gastrointestinal system: gastritis , gastroenteritis , colitis , and enterocolitis ....
  • Pernicious anemia
    Pernicious anemia

    Pernicious anemia is a form of megaloblastic anemia due to vitamin B-12 Avitaminosis, caused by impaired absorption of vitamin B-12 due to the absence of intrinsic factor in the setting of atrophic gastritis, and more specifically of loss of stomach parietal cells....
  • Aplastic anemia
    Aplastic anemia

    Aplastic anemia is a condition where bone marrow does not produce sufficient new cell s to replenish blood cells.The term 'aplastic' means the marrow suffers from an aplasia that renders it unable to function properly....
  • Chronic myelogenous leukemia
    Chronic myelogenous leukemia

    Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood....


Other notes
Leukocyte alkaline phosphatase (LAP) is found within white blood cell
White blood cell

White blood cells , or leukocytes , are cell of the immune system defending the body against both infectious disease and foreign materials....
s. Blood levels of LAP can help in the diagnosis of chronic myelogenous leukemia
Chronic myelogenous leukemia

Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood....
 (CML), polycythemia vera
Polycythemia vera

Primary polycythemia, often called polycythemia vera , polycythemia rubra vera , or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow and occasionally in the kidneys....
 (PV), essential thrombocytosis (ET), primary myelofibrosis (PM), and the leukemoid reaction
Leukemoid reaction

The term leukemoid reaction, also referred to as transient myeloproliferative disorder, describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection ....
.

See also

  • Liver function tests
    Liver function tests

    Liver function tests , which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver....
  • Acid phosphatase
    Acid phosphatase

    Acid phosphatase is a phosphatase, a type of enzyme, used to free attached phosphate groups from other molecules during digestion. It is basically a phosphomonoesterase....


External links

  • [Veritas Microplate Luminometer Method for Alkaline Phosphatase