Ball and stick model of alkaline phosphatase

Alkaline phosphatase (ALP) (EC 3.1.3.1) 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. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... armchair conformational isomerism of cyclohexane. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... In biochemistry, a hydrolase is an enzyme that can break a chemical bond by hydrolysis. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... A phosphate, in inorganic chemistry, is a salt of phosphoric acid. ... A nucleotide is an organic molecule consisting of a heterocyclic nucleobase (a purine or a pyrimidine), a pentose sugar (deoxyribose in DNA or ribose in RNA), and a phosphate or polyphosphate group. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and other animals. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... The common (Arrhenius) definition of a base is a chemical compound that either donates hydroxide ions or absorbs hydrogen ions when dissolved in water. ...

Bacterial

In bacteria, alkaline phosphatase is located in the periplasmic space, external to the cell membrane. 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, and degradation, 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. 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 and metabolism suggest that other, more subtle, purposes for the enzyme may also play a role for the cell. In the laboratory, however, mutant Escherichia coli lacking alkaline phosphatase survive quite well, as do mutants unable to shut off alkaline phosphatase production. Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... The periplasmic space is the space seen between the plasma membrane and the outer membrane in the gram-negative bacteria. ... Look up cell membrane in Wiktionary, the free dictionary. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) Denaturation is the alteration of a protein or nucleic acids shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no... Look up degradation in Wiktionary, the free dictionary. ... An organic compound is any of a large class of chemical compounds whose molecules contain carbon, with exception of carbides, carbonates and carbon oxides. ... Structure of the coenzyme adenosine triphosphate, a central intermediate in energy metabolism. ... This article does not cite any references or sources. ... This article is about biological mutants. ... E. coli redirects here. ...

Use in research

The most common alkaline phosphatases used in research are:

• Bacterial alkaline phosphatase (BAP), from Escherichia coli C4 cells
• Shrimp alkaline phosphatase (SAP), from a species of arctic shrimp (Pandalus borealis)
• Calf intestine alkaline phosphatase (CIAP), from calf intestine
• Placental alkaline phosphatase (PLAP) 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 laboratories, since DNA normally possesses phosphate groups on the 5' end. Removing these phosphates prevents the DNA from ligating (the 5' end attaching to the 3' end of another molecule), thereby preventing DNA degradation until the next step of the process for which it is 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. E. coli redirects here. ... Superfamilies Alpheoidea Atyoidea Bresilioidea Campylonotoidea Crangonoidea Galatheacaridoidea Nematocarcinoidea Oplophoroidea Palaemonoidea Pandaloidea Pasiphaeoidea Procaridoidea Processoidea Psalidopodoidea Stylodactyloidea True shrimp are swimming, decapod crustaceans classified in the infraorder Caridea, found widely around the world in both fresh and salt water. ... Binomial name Pandalus borealis Krøyer, 1838 Pandalus borealis (also called Pandalus eous) is a species of shrimp found in cold parts of the Atlantic and Pacific Oceans. ... For the anatomical feature, see calf muscle. ... In anatomy, the intestine is the segment of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine. ... The placenta is a sack of fat present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy). ... Molecular biology is the study of biology at a molecular level. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... In biochemistry, a ligase (from the Latin verb ligāre — to bind or to glue together) is an enzyme that can catalyse the joining of two molecules by forming a new chemical bond, with accompanying hydrolysis of adenosine triphosphate or other similar molecules. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... It has been suggested that this article or section be merged into Isotopic labeling. ...

Another important use of alkaline phosphatase is as a label for enzyme immunoassays. An immunoassay is a biochemical test that measures the level of bodily reaction to a foreign object. ...

One common use in the dairy industry is as a marker of pasteurisation. 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 placental (PLAP and SEAP) are inhibited by homoarginine and similarly all except the intestinal and placental ones are blocked by levamisole. Heating for ~2 hours at 65^oC inactivated most isoenzymes except Placental isoforms (PLAP and SEAP). The placenta is a sack of fat present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy). ... Levamisole hydrochloride (Ergamisol®) is an antibiotic medication used in combination with fluorouracil to treat colon cancer. ...

Human

The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 2 is one of the 23 pairs of chromosomes in humans. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Alkaline phosphatase, liver/bone/kidney, also known as ALPL, is a human gene. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Alkaline phosphatase, liver/bone/kidney, also known as ALPL, is a human gene. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 1 is, by convention, the designation for the largest human chromosome. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 2 is one of the 23 pairs of chromosomes in humans. ...

Physiology

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. The optimal pH for the enzyme activity is pH=10^{[citation needed]} in standard conditions (298K,1 atm). For the bird, see Liver bird. ... A bile duct is any of a number of long tube-like structures that carry bile. ... The kidneys are the organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... This article is about the skeletal organs. ... The placenta is a sack of fat present in placental vertebrates, such as some mammals and sharks during gestation (pregnancy). ...

Diagnostic use

Blood plasma (serum) levels of ALP are typically 20-70 units per liter in adults (Reference - USMLE),^{[citation needed]} depending on the assay and local normal guidelines (. Levels are significantly higher in children and pregnant women. Blood plasma is the liquid component of blood, in which the blood cells are suspended. ...

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 can confirm the source of the ALP. Heat stability also distinguishes bone and liver isoenzymes ("bone burns, liver lasts"). Isozymes, (or isoenzymes) are isoforms (closely related variants) of enzymes. ... For specific types of electrophoresis (for example, the process of administering medicine, iontophoresis), see electrophoresis (disambiguation). ...

• Liver (Liver ALP):
  • Cholestasis, cholecystitis, cholangitis, cirrhosis, hepatitis, fatty liver, liver tumor, liver metastases, drug intoxication
    • N.B. concurrently elevated GGT(gamma glutamyl transpeptidase) helps rule in favor of liver metastasis (rather than bone, kidney, etc.) when assessing spread of cancer.
  • Drugs: e.g. verapamil, carbamazepine, phenytoin, erythromycin, allopurinol, ranitidine
• Bone disease (Bone ALP):
  • Paget's disease, osteosarcoma, bone metastases of prostatic cancer (High / very high ALP values)
  • Other bone metastases
  • Fractured bone
  • Multiple myeloma (only when associated with fractures)
• Skeletal involvement of other primary diseases:
  • Osteomalacia, rickets, vitamin D deficiency, (Moderate rise)
  • Malignant tumors (ALP originating from tumor)
  • Renal disease (secondary hyperparathyroidism)
  • Primary hypothyroidism
• Polycythemia vera
• Myelofibrosis
• Leukemoid reaction to infection
• Women using hormonal contraception
• Pregnancy
• Biliary obstruction
• Transient hyperphosphatasaemia of infancy: benign, often associated with infection

For the bird, see Liver bird. ... In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. ... Cholecystitis is inflammation of the gall bladder. ... Cholangitis is one of a number of problems associated with the bile duct. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... Hepatitis (plural hepatitides) implies injury to liver characterised by presence of inflammatory cells in the liver tissue. ... Different stages of liver damage Fatty liver (also known as steatorrhoeic hepatosis or steatosis hepatis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis. ... Hepatic tumours are tumours or growths on or in the liver. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body (e. ... Gamma glutamyl transferase (GGT or GGTP, or Gamma-GT) (EC 2. ... This article does not cite any references or sources. ... Verapamil (brand names: Isoptin®, Verelan®, Calan®) is a medical drug that acts as an L-type calcium channel blocker. ... Carbamazepine (CBZ) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. ... Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK, by Parke-Davis, now part of Pfizer) is a commonly used antiepileptic. ... Erythromycin is a macrolide antibiotic which 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 is a drug used primarily to treat conditions arising from excess uric acid, most notably chronic gout. ... Ranitidine (INN) (IPA: ) is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). ... This article is about the skeletal organs. ... Sir James Paget, a prolific surgeon and pathologist, described several diseases, all called Pagets disease: The term is most commonly used to refer to Pagets disease of bone It can also mean Pagets disease of the breast Or: Pagets disease of the penis. ... Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. ... Prostate cancer is a group of cancerous cells (a malignant tumor) that begins most often in the outer part of the prostate. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... A fractured bone in a living person is typically treated by restoring the fractured pieces of bone to their natural positions (if necessary), and maintaining those positions while the bone heals. ... Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahlers disease after Otto Kahler) is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. ... Skeleton is also a winter sport: see skeleton (sport). ... Osteomalacia is a softening of the bones, resulting from defective bone mineralisation. ... Rickets is a softening of the bones in children potentially leading to fractures and deformity. ... Tumor (American English) or tumour (British English) originally means swelling, and is sometimes still used with that meaning. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). ... This article or section does not cite its references or sources. ... Primary polycythemia, often called polycythemia vera (PCV), polycythemia rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow. ... Myelofibrosis with myeloid metaplasia, also known as agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, and primary myelofibrosis,[1] was first described in 1879 and is currently classified as a myeloproliferative disease caused by the growth and proliferation of an abnormal bone marrow stem cell, resulting in the replacement of the bone... The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). ... Hormonal contraception refers to birth control methods that act on the hormonal system. ... This article is about human pregnancy in biological females. ... X-Ray of the bile duct during a laprascopic cholecystectomy A bile duct is any of a number of long tube-like structures that carry bile. ... Look up Benign in Wiktionary, the free dictionary. ...

Lowered levels (hypophosphatasemia)

• Hypophosphatasia, an autosomal recessive disease
• Postmenopausal women receiving estrogen therapy because of osteoporosis
• Men with recent heart surgery, malnutrition, magnesium deficiency, hypothyroidism or severe anemia
• Children with achondroplasia and cretinism
• Children after a severe enteritis
• Pernicious anemia
• Aplastic anemia
• Chronic myelogenous leukemia

Hypophosphatasia is a rare inherited metabolic disease of decreased tissue nonspecific alkaline phosphatase (TNSALP) and defective bone mineralization. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Menopause is the physiological cessation of menstrual cycles associated with advancing age in women. ... Hormone replacement therapy (HRT) is a system of medical treatment for postmenopausal women, based on the assumption that it may prevent discomfort and health problems caused by diminished circulating estrogen hormones. ... Osteoporosis is a disease of bone - leading to an increased risk of fracture. ... Cardiac surgery is surgery on the heart, typically to correct congenital heart disease or the complications of ischaemic heart disease or valve problems caused by endocarditis. ... Percentage of population affected by malnutrition by country, according to United Nations statistics. ... General Name, symbol, number magnesium, Mg, 12 Chemical series alkaline earth metals Group, period, block 2, 3, s Appearance silvery white solid at room temp Standard atomic weight 24. ... This article or section does not cite its references or sources. ... This article discusses the medical condition. ... Circus Busch, 1906 Achondroplasia is a type of autosomal dominant genetic disorder that is a common cause of dwarfism. ... This article is about the medical term. ... Enteritis is the inflammation of the small intestine (inflammation of the large intestine is termed colitis). ... Pernicious anemia (also known as Biermers anaemia or Addisons anaemia or Addison-Biermer anaemia) is a form of megaloblastic anaemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12 in the setting of atrophic gastritis, and more specifically of loss of gastric parietal cells. ... Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. ... Chronic myelogenous leukemia (CML) is a form of chronic leukemia characterized by increased and unregulated clonal production of predominantly myeloid cells in the bone marrow. ...

Other notes

Leukocyte alkaline phosphatase (LAP) is found within white blood cells. Blood levels of LAP can help in the diagnosis of chronic myelogenous leukemia (CML) and leukemoid reaction. Alkaline phosphatase, drawn from PDB 1ANI. Alkaline phosphatase (ALP) (EC 3. ... White Blood Cells redirects here. ... Chronic myelogenous leukemia (CML) is a form of chronic leukemia characterized by increased and unregulated clonal production of predominantly myeloid cells in the bone marrow. ... The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). ...

See also

• Liver function tests
• Acid phosphatase

Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patients liver. ... Acid phosphatase is a phosphatase, a type of enzyme, used to free attached phosphate groups from other molecules during digestion. ...

External links

• IUBMB Enzyme Nomenclature
• Structure and Mechanism of Alkaline Phosphatase