Alkaline phosphatase

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Alkaline phosphatase_table_infobox_0

Alkaline phosphataseAlkaline phosphatase_header_cell_0_0_0
IdentifiersAlkaline phosphatase_header_cell_0_1_0
EC numberAlkaline phosphatase_header_cell_0_2_0 Alkaline phosphatase_cell_0_2_1
CAS numberAlkaline phosphatase_header_cell_0_3_0 Alkaline phosphatase_cell_0_3_1
DatabasesAlkaline phosphatase_header_cell_0_4_0
IntEnzAlkaline phosphatase_header_cell_0_5_0 Alkaline phosphatase_cell_0_5_1
BRENDAAlkaline phosphatase_header_cell_0_6_0 Alkaline phosphatase_cell_0_6_1
ExPASyAlkaline phosphatase_header_cell_0_7_0 Alkaline phosphatase_cell_0_7_1
KEGGAlkaline phosphatase_header_cell_0_8_0 Alkaline phosphatase_cell_0_8_1
MetaCycAlkaline phosphatase_header_cell_0_9_0 Alkaline phosphatase_cell_0_9_1
Alkaline phosphatase_header_cell_0_10_0 Alkaline phosphatase_cell_0_10_1
PDB structuresAlkaline phosphatase_header_cell_0_11_0 Alkaline phosphatase_cell_0_11_1
Gene OntologyAlkaline phosphatase_header_cell_0_12_0 /Alkaline phosphatase_cell_0_12_1
SearchPMCPubMedNCBIAlkaline phosphatase_cell_0_13_0
SearchAlkaline phosphatase_header_cell_0_14_0
PMCAlkaline phosphatase_header_cell_0_15_0 Alkaline phosphatase_cell_0_15_1
PubMedAlkaline phosphatase_header_cell_0_16_0 Alkaline phosphatase_cell_0_16_1
NCBIAlkaline phosphatase_header_cell_0_17_0 Alkaline phosphatase_cell_0_17_1

Alkaline phosphatase_table_infobox_1

Alkaline phosphataseAlkaline phosphatase_header_cell_1_0_0
IdentifiersAlkaline phosphatase_header_cell_1_1_0
SymbolAlkaline phosphatase_header_cell_1_2_0 Alk_phosphataseAlkaline phosphatase_cell_1_2_1
PfamAlkaline phosphatase_header_cell_1_3_0 Alkaline phosphatase_cell_1_3_1
InterProAlkaline phosphatase_header_cell_1_4_0 Alkaline phosphatase_cell_1_4_1
SMARTAlkaline phosphatase_header_cell_1_5_0 Alkaline phosphatase_cell_1_5_1
PROSITEAlkaline phosphatase_header_cell_1_6_0 Alkaline phosphatase_cell_1_6_1
SCOP2Alkaline phosphatase_header_cell_1_7_0 / /Alkaline phosphatase_cell_1_7_1
Available protein structures:Pfam
 PDB; ; PDBsumPDB​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​Alkaline phosphatase_cell_1_8_0
Available protein structures:Alkaline phosphatase_header_cell_1_9_0
PfamAlkaline phosphatase_header_cell_1_10_0 /Alkaline phosphatase_cell_1_10_1
PDBAlkaline phosphatase_header_cell_1_11_0 ; ;Alkaline phosphatase_cell_1_11_1
PDBsumAlkaline phosphatase_header_cell_1_12_0 Alkaline phosphatase_cell_1_12_1
PDBAlkaline phosphatase_header_cell_1_13_0 ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​, ​Alkaline phosphatase_cell_1_13_1

Alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos) (EC ), or basic phosphatase, is a homodimeric protein enzyme of 86 kilodaltons. Alkaline phosphatase_sentence_0

Each monomer contains five cysteine residues, two zinc atoms and one magnesium atom crucial to its catalytic function, and it is optimally active at alkaline pH environments. Alkaline phosphatase_sentence_1

ALP has the physiological role of dephosphorylating compounds. Alkaline phosphatase_sentence_2

The enzyme is found across a multitude of organisms, prokaryotes and eukaryotes alike, with the same general function but in different structural forms suitable to the environment they function in. Alkaline phosphatase_sentence_3

Alkaline phosphatase is found in the periplasmic space of E. Alkaline phosphatase_sentence_4 coli bacteria. Alkaline phosphatase_sentence_5

This enzyme is heat stable and has its maximum activity at high pH. Alkaline phosphatase_sentence_6

In humans, it is found in many forms depending on its origin within the body – it plays an integral role in metabolism within the liver and development within the skeleton. Alkaline phosphatase_sentence_7

Due to its widespread prevalence in these areas, its concentration in the bloodstream is used by diagnosticians as a biomarker in helping determine diagnoses such as hepatitis or osteomalacia. Alkaline phosphatase_sentence_8

The level of alkaline phosphatase in the blood is checked through the ALP test, which is often part of routine blood tests. Alkaline phosphatase_sentence_9

The levels of this enzyme in the blood depend on factors such as age, sex, or blood type. Alkaline phosphatase_sentence_10

Blood levels of alkaline phosphatase also increase by two to four times during pregnancy. Alkaline phosphatase_sentence_11

This is a result of additional alkaline phosphatase produced by the placenta. Alkaline phosphatase_sentence_12

Additionally, abnormal levels of alkaline phosphatase in the blood could indicate issues relating to the liver, gall bladder or bones. Alkaline phosphatase_sentence_13

Kidney tumors and infections as well as malnutrition have also shown abnormal level of alkaline phosphatase in blood. Alkaline phosphatase_sentence_14

Alkaline phosphatase levels in a cell can be measured through a process called "The scoring method". Alkaline phosphatase_sentence_15

A blood smear is usually taken and stained to categorize each leukocyte into specific "leukocyte alkaline phosphatase indices". Alkaline phosphatase_sentence_16

This marker is designed to distinguish leukocytes and determine different enzyme activity from each sample's extent of staining. Alkaline phosphatase_sentence_17

Bacterial Alkaline phosphatase_section_0

In Gram-negative bacteria, such as Escherichia coli (E. coli), alkaline phosphatase is located in the periplasmic space, external to the inner cell membrane and within the peptidoglycan portion of the cell wall. Alkaline phosphatase_sentence_18

Since the periplasmic gap is more prone to environmental variation than the inner cell, alkaline phosphatase is suitably resistant to inactivation, denaturation, or degradation. Alkaline phosphatase_sentence_19

This characteristic of the enzyme is uncommon to many other proteins. Alkaline phosphatase_sentence_20

The precise structure and function of the four isozymes (Int in E.coli) are solely geared to supply a source of inorganic phosphate when the environment lacks this metabolite. Alkaline phosphatase_sentence_21

The four enzymes are dependent upon the location of the tissue expression. Alkaline phosphatase_sentence_22

The four sites of tissue expression are the Intestinal AlP, Placental ALP, Germ Cell ALP and Liver/Bone/Kidney ALP. Alkaline phosphatase_sentence_23

The inorganic phosphates produced by these isozymes are then bound to carrier proteins which deliver the inorganic phosphates to a specific high-affinity transport system, known as the Pst system, which transports phosphate across the cytoplasmic membrane. Alkaline phosphatase_sentence_24

While the outer membrane of E. coli contains porins that are permeable to phosphorylated compounds, the inner membrane does not. Alkaline phosphatase_sentence_25

Then, an issue arises in how to transport such compounds across the inner membrane and into the cytosol. Alkaline phosphatase_sentence_26

Surely, with the strong anionic charge of phosphate groups along with the remainder of the compound they are very much immiscible in the nonpolar region of the bilayer. Alkaline phosphatase_sentence_27

The solution arises in cleaving the phosphate group away from the compound via ALP. Alkaline phosphatase_sentence_28

In effect, along with the concomitant compound the phosphate was bound to, this enzyme yields pure inorganic phosphate which can be ultimately targeted by the phosphate-specific transport system (Pst system) for translocation into the cytosol. Alkaline phosphatase_sentence_29

As such, 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. Alkaline phosphatase_sentence_30

Alkaline phosphatase is a zinc-containing dimeric enzyme with the MW: 86,000 Da, each subunit containing 429 amino acids with four cysteine residues linking the two subunits. Alkaline phosphatase_sentence_31

Alkaline phosphatase contains four Zn ions and two Mg ions, with Zn occupying active sites A and B, and Mg occupying site C, so the fully active native alkaline phosphatase is referred to as (ZnAZnBMgC)2 enzyme. Alkaline phosphatase_sentence_32

The mechanism of action of alkaline phosphatase involves the geometric coordination of the substrate between the Zn ions in the active sites, whereas the Mg site doesn't appear to be close enough to directly partake in the hydrolysis mechanism, however, it may contribute to the shape of the electrostatic potential around the active center. Alkaline phosphatase_sentence_33

Alkaline phosphatase has a Km of 8.4 x 10. Alkaline phosphatase_sentence_34

Alkaline phosphatase in E. coli is uncommonly soluble and active within elevated temperature conditions such as 80 °C. Alkaline phosphatase_sentence_35

Due to the kinetic energy induced by this temperature the weak hydrogen bonds and hydrophobic interactions of common proteins become degraded and therefore coalesce and precipitate. Alkaline phosphatase_sentence_36

However, upon dimerization of ALP the bonds maintaining its secondary and tertiary structures are effectively buried such that they are not affected as much at this temperature. Alkaline phosphatase_sentence_37

Furthermore, even at more elevated temperatures such as 90 °C ALP has the uncommon characteristic of reverse denaturation. Alkaline phosphatase_sentence_38

Due to this, while ALP ultimately denatures at about 90 °C it has the added ability to accurately reform its bonds and return to its original structure and function once cooled back down. Alkaline phosphatase_sentence_39

Alkaline phosphatase in E. coli is located in the periplasmic space and can thus be released using techniques that weaken the cell wall and release the protein. Alkaline phosphatase_sentence_40

Due to the location of the enzyme, and the protein layout of the enzyme, the enzyme is in solution with a smaller amount of proteins than there are in another portion of the cell. Alkaline phosphatase_sentence_41

The proteins' heat stability can also be taken advantage of when isolating this enzyme (through heat denaturation). Alkaline phosphatase_sentence_42

In addition, alkaline phosphatase can be assayed using p-Nitrophenyl phosphate. Alkaline phosphatase_sentence_43

A reaction where alkaline phosphatase dephosphorylates the non-specific substrate, p-Nitrophenyl phosphate in order to produce p-Nitrophenol(PNP) and inorganic phosphate. Alkaline phosphatase_sentence_44

PNP's yellow color, and its λmax at 410 allows spectrophotometry to determine important information about enzymatic activity. Alkaline phosphatase_sentence_45

Some complexities of bacterial regulation and metabolism suggest that other, more subtle, purposes for the enzyme may also play a role for the cell. Alkaline phosphatase_sentence_46

In the laboratory, however, mutant Escherichia coli lacking alkaline phosphatase survive quite well, as do mutants unable to shut off alkaline phosphatase production. Alkaline phosphatase_sentence_47

The optimal pH for the activity of the E. coli enzyme is 8.0 while the bovine enzyme optimum pH is slightly higher at 8.5. Alkaline phosphatase_sentence_48

Alkaline phosphatase accounts for 6% of all proteins in derepressed cells. Alkaline phosphatase_sentence_49

Intragenic complementation Alkaline phosphatase_section_1

When multiple copies of a polypeptide encoded by a gene form an aggregate, this protein structure is referred to as a multimer. Alkaline phosphatase_sentence_50

When a multimer is formed from polypeptides produced by two different mutant alleles of a particular gene, the mixed multimer may exhibit greater functional activity than the unmixed multimers formed by each of the mutants alone. Alkaline phosphatase_sentence_51

In such a case, the phenomenon is referred to as intragenic complementation. Alkaline phosphatase_sentence_52

E. coli alkaline phosphatase, a dimer enzyme, exhibits intragenic complementation. Alkaline phosphatase_sentence_53

When particular mutant versions of alkaline phosphatase were combined, the heterodimeric enzymes formed as a result exhibited a higher level of activity than would be expected based on the relative activities of the parental enzymes. Alkaline phosphatase_sentence_54

These findings indicated that the dimer structure of E.coli alkaline phosphatase allows cooperative interactions between the constituent monomers that can generate a more functional form of the holoenzyme. Alkaline phosphatase_sentence_55

Use in research Alkaline phosphatase_section_2

By changing the amino acids of the wild-type alkaline phosphatase enzyme produced by Escherichia coli, a mutant alkaline phosphatase is created which not only has a 36-fold increase in enzyme activity, but also retains thermal stability. Alkaline phosphatase_sentence_56

Typical uses in the lab for alkaline phosphatases include removing phosphate monoesters to prevent self-ligation, which is undesirable during plasmid DNA cloning. Alkaline phosphatase_sentence_57

Common alkaline phosphatases used in research include: Alkaline phosphatase_sentence_58

Alkaline phosphatase_unordered_list_0

  • Shrimp alkaline phosphatase (SAP), from a species of Arctic shrimp (Pandalus borealis). This phosphatase is easily inactivated by heat, a useful feature in some applications.Alkaline phosphatase_item_0_0
  • Calf-intestinal alkaline phosphatase (CIP)Alkaline phosphatase_item_0_1
  • Placental alkaline phosphatase (PLAP) and its C terminally truncated version that lacks the last 24 amino acids (constituting the domain that targets for GPI membrane anchoring) – the secreted alkaline phosphatase (SEAP). It presents certain characteristics like heat stability, substrate specificity, and resistance to chemical inactivation.Alkaline phosphatase_item_0_2
  • Human-intestinal alkaline phosphatase. The human body has multiple types of alkaline phosphatase present, which are determined by a minimum of three gene loci. Each one of these three loci controls a different kind of alkaline phosphatase isozyme. However, the development of this enzyme can be strictly regulated by other factors such as thermostability, electrophoresis, inhibition, or immunology.Alkaline phosphatase_item_0_3

Human-intestinal ALPase shows around 80% homology with bovine intestinal ALPase, which holds true their shared evolutionary origins. Alkaline phosphatase_sentence_59

That same bovine enzyme has more than 70% homology with human placental enzyme. Alkaline phosphatase_sentence_60

However, the human intestinal enzyme and the placental enzyme only share 20% homology despite their structural similarities. Alkaline phosphatase_sentence_61

Alkaline phosphatase has become a useful tool in molecular biology laboratories, since DNA normally possesses phosphate groups on the 5' end. Alkaline phosphatase_sentence_62

Removing these phosphates prevents the DNA from ligating (the 5' end attaching to the 3' 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. Alkaline phosphatase_sentence_63

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. Alkaline phosphatase_sentence_64

Another important use of alkaline phosphatase is as a label for enzyme immunoassays. Alkaline phosphatase_sentence_65

Undifferentiated pluripotent stem cells have elevated levels of alkaline phosphatase on their cell membrane, therefore alkaline phosphatase staining is used to detect these cells and to test pluripotency (i.e., embryonic stem cells or embryonal carcinoma cells). Alkaline phosphatase_sentence_66

There is a positive correlation between serum bone alkaline phosphatase (B-ALP) levels and bone formation in humans, although its use as a biomarker in clinical practice is not recommended. Alkaline phosphatase_sentence_67

Ongoing research Alkaline phosphatase_section_3

Current researchers are looking into the increase of tumor necrosis factor-α and its direct effect on the expression of alkaline phosphatase in vascular smooth muscle cells as well as how alkaline phosphatase (AP) affects the inflammatory responses and may play a direct role in preventing organ damage. Alkaline phosphatase_sentence_68

Alkaline phosphatase_unordered_list_1

  • Alkaline phosphatase (AP) affects the inflammatory responses in patients with Chronic kidney disease and is directly associated with Erythropoiesis stimulating agent resistant anemia.Alkaline phosphatase_item_1_4
  • Intestinal alkaline phosphatase (IAP) and the mechanism it uses to regulate pH and ATP hydrolysis in rat duodenum.Alkaline phosphatase_item_1_5
  • Testing the effectiveness of the inhibitor and its impact on IAP in acute intestinal inflammation as well as explore the molecular mechanisms of IAP in "ameliorating intestinal permeability."Alkaline phosphatase_item_1_6

Dairy industry Alkaline phosphatase_section_4

Main article: Pasteurization § Verification Alkaline phosphatase_sentence_69

Alkaline phosphatase is commonly used in the dairy industry as an indicator of successful pasteurization. Alkaline phosphatase_sentence_70

This is because the most heat stable bacterium found in milk, Mycobacterium paratuberculosis, is destroyed by temperatures lower than those required to denature ALP. Alkaline phosphatase_sentence_71

Therefore, ALP presence is ideal for indicating failed pasteurization. Alkaline phosphatase_sentence_72

Pasteurization verification is typically performed by measuring the fluorescence of a solution which becomes fluorescent when exposed to active ALP. Alkaline phosphatase_sentence_73

Fluorimetry assays are required by milk producers in the UK to prove alkaline phosphatase has been denatured, as p-Nitrophenylphosphate tests are not considered accurate enough to meet health standards. Alkaline phosphatase_sentence_74

Alternatively the colour change of a para-Nitrophenylphosphate substrate in a buffered solution (Aschaffenburg Mullen Test) can be used. Alkaline phosphatase_sentence_75

Raw milk would typically produce a yellow colouration within a couple of minutes, whereas properly pasteurised milk should show no change. Alkaline phosphatase_sentence_76

There are exceptions to this, as in the case of heat-stable alkaline phophatases produced by some bacteria, but these bacteria should not be present in milk. Alkaline phosphatase_sentence_77

Inhibitors Alkaline phosphatase_section_5

All mammalian alkaline phosphatase isoenzymes except placental (PALP and SEAP) are inhibited by homoarginine, and, in similar manner, all except the intestinal and placental ones are blocked by levamisole. Alkaline phosphatase_sentence_78

Phosphate is another inhibitor which competitively inhibits alkaline phosphatase. Alkaline phosphatase_sentence_79

Another known example of an alkaline phosphatase inhibitor is [(4-Nitrophenyl)methyl]phosphonic acid. Alkaline phosphatase_sentence_80

In metal contaminated soil, alkaline phosphatase are inhibited by Cd (Cadmium). Alkaline phosphatase_sentence_81

In addition, temperature enhances the inhibition of Cd on ALP activity, which is shown in the increasing values of Km. Alkaline phosphatase_sentence_82

Human Alkaline phosphatase_section_6

Physiology Alkaline phosphatase_section_7

In humans, alkaline phosphatase is present in all tissues throughout the body, but is particularly concentrated in the liver, bile duct, kidney, bone, intestinal mucosa and placenta. Alkaline phosphatase_sentence_83

In the serum, two types of alkaline phosphatase isozymes predominate: skeletal and liver. Alkaline phosphatase_sentence_84

During childhood the majority of alkaline phosphatase are of skeletal origin. Alkaline phosphatase_sentence_85

Humans and most other mammals contain the following alkaline phosphatase isozymes: Alkaline phosphatase_sentence_86

Alkaline phosphatase_unordered_list_2

  • ALPI – intestinal (molecular weight of 150 kDa)Alkaline phosphatase_item_2_7
  • ALPL – tissue-nonspecific (expressed mainly in liver, bone, and kidney)Alkaline phosphatase_item_2_8
  • ALPP – placental (Regan isozyme)Alkaline phosphatase_item_2_9
  • ALPG – germ cellAlkaline phosphatase_item_2_10

Four genes encode the four isozymes. Alkaline phosphatase_sentence_87

The gene for tissue-nonspecific alkaline phosphatase is located on chromosome 1, and the genes for the other three isoforms are located on chromosome 2. Alkaline phosphatase_sentence_88

Intestinal alkaline phosphatase Alkaline phosphatase_section_8

Intestinal alkaline phosphatase is secreted by enterocytes, and seems to play a pivotal role in intestinal homeostasis and protection as well as in mediation of inflammation via repression of the downstream Toll-like receptor (TLR)-4-dependent and MyD88-dependent inflammatory cascade. Alkaline phosphatase_sentence_89

It dephosphorylates toxic/inflammatory microbial ligands like lipopolysaccharides, unmethylated cytosine-guanine dinucleotides, flagellin, and extracellular nucleotides such as uridine diphosphate or ATP. Alkaline phosphatase_sentence_90

Thus, altered IAP expression has been implicated in chronic inflammatory diseases such as inflammatory bowel disease (IBD). Alkaline phosphatase_sentence_91

It also seems to regulate lipid absorption and bicarbonate secretion in the duodenal mucosa, which regulates the surface pH. Alkaline phosphatase_sentence_92

In cancer cells Alkaline phosphatase_section_9

Studies show that the alkaline phosphatase protein found in cancer cells is similar to that found in nonmalignant body tissues and that the protein originates from the same gene in both. Alkaline phosphatase_sentence_93

One study compared the enzymes of liver metastases of giant-cell lung carcinoma and nonmalignant placental cells. Alkaline phosphatase_sentence_94

The two were similar in NH2-terminal sequence, peptide map, subunit molecular weight, and isoelectronic point. Alkaline phosphatase_sentence_95

In a different study in which scientists examined alkaline phosphatase protein presence in a human colon cancer cell line, also known as HT-29, results showed that the enzyme activity was similar to that of the non-malignant intestinal type. Alkaline phosphatase_sentence_96

However, this study revealed that without the influence of sodium butyrate, alkaline phosphatase activity is fairly low in cancer cells. Alkaline phosphatase_sentence_97

A study based on sodium butyrate effects on cancer cells conveys that it has an effect on androgen receptor co-regulator expression, transcription activity, and also on histone acetylation in cancer cells. Alkaline phosphatase_sentence_98

This explains why the addition of sodium butyrate show increased activity of alkaline phosphatase in the cancer cells of the human colon. Alkaline phosphatase_sentence_99

In addition, this further supports the theory that alkaline phosphatase enzyme activity is actually present in cancer cells. Alkaline phosphatase_sentence_100

In another study, choriocarcinoma cells were grown in the presence of 5-bromo-2’-deoxyuridine (BrdUrd) and results conveyed a 30- to 40- fold increase in alkaline phosphatase activity. Alkaline phosphatase_sentence_101

This procedure of enhancing the activity of the enzyme is known as enzyme induction. Alkaline phosphatase_sentence_102

The evidence shows that there is in fact activity of alkaline phosphatase in tumor cells, but it is minimal and needs to be enhanced. Alkaline phosphatase_sentence_103

Results from this study further indicate that activities of this enzyme vary among the different choriocarcinoma cell lines and that the activity of the alkaline phosphatase protein in these cells is lower than in the non-malignant placenta cells. Alkaline phosphatase_sentence_104

but levels are significantly higher in children and pregnant women. Alkaline phosphatase_sentence_105

Blood tests should always be interpreted using the reference range from the laboratory that performed the test. Alkaline phosphatase_sentence_106

High ALP levels can occur if the bile ducts are obstructed. Alkaline phosphatase_sentence_107

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). Alkaline phosphatase_sentence_108

ALP is much more elevated in metastatic prostate cancer cells than non-metastatic prostate cancer cells. Alkaline phosphatase_sentence_109

High levels of ALP in prostate cancer patients is associated with a significant decrease in survival. Alkaline phosphatase_sentence_110

Levels are also elevated in people with untreated coeliac disease. Alkaline phosphatase_sentence_111

Lowered levels of ALP are less common than elevated levels. Alkaline phosphatase_sentence_112

The source of elevated ALP levels can be deduced by obtaining serum levels of gamma glutamyltransferase (GGT). Alkaline phosphatase_sentence_113

Concomitant increases of ALP with GGT should raise the suspicion of hepatobiliary disease. Alkaline phosphatase_sentence_114

Some diseases do not affect the levels of alkaline phosphatase, for example, hepatitis C. A high level of this enzyme does not reflect any damage in the liver, even though high alkaline phosphatase levels may result from a blockage of flow in the biliary tract or an increase in the pressure of the liver. Alkaline phosphatase_sentence_115

Elevated levels Alkaline phosphatase_section_10

Main article: Elevated alkaline phosphatase Alkaline phosphatase_sentence_116

If it is unclear why alkaline phosphatase is elevated, isoenzyme studies using electrophoresis can confirm the source of the ALP. Alkaline phosphatase_sentence_117

Skelphosphatase (which is localized in osteoblasts and extracellular layers of newly synthesized matrix) is released into circulation by a yet unclear mechanism. Alkaline phosphatase_sentence_118

Placental alkaline phosphatase is elevated in seminomas and active forms of rickets, as well as in the following diseases and conditions: Alkaline phosphatase_sentence_119

Alkaline phosphatase_unordered_list_3

Lowered levels Alkaline phosphatase_section_11

The following conditions or diseases may lead to reduced levels of alkaline phosphatase: Alkaline phosphatase_sentence_120

Alkaline phosphatase_unordered_list_4

In addition, oral contraceptives have been demonstrated to reduce alkaline phosphatase. Alkaline phosphatase_sentence_121

Prognostic uses Alkaline phosphatase_section_12

Measuring alkaline phosphatase (along with prostate specific antigen) during, and after six months of hormone treated metastatic prostate cancer was shown to predict the survival of patients. Alkaline phosphatase_sentence_122

Leukocyte alkaline phosphatase Alkaline phosphatase_section_13

Leukocyte alkaline phosphatase (LAP) is found within mature white blood cells. Alkaline phosphatase_sentence_123

White blood cell levels of LAP can help in the diagnosis of certain conditions. Alkaline phosphatase_sentence_124

Alkaline phosphatase_unordered_list_5

Structure and properties Alkaline phosphatase_section_14

Alkaline phosphatase is homodimeric enzyme, meaning it is formed with two molecules. Alkaline phosphatase_sentence_125

Three metal ions, two Zn and one Mg, are contained in the catalytic sites, and both types are crucial for enzymatic activity to occur. Alkaline phosphatase_sentence_126

The enzymes catalyze the hydrolysis of monoesters in phosphoric acid which can additionally catalyze a transphosphorylation reaction with large concentrations of phosphate acceptors. Alkaline phosphatase_sentence_127

While the main features of the catalytic mechanism and activity are conserved between mammalian and bacterial alkaline phosphate, mammalian alkaline phosphatase has a higher specific activity and Km values thus a lower affinity, more alkaline pH optimum, lower heat stability, and are typically membrane bound and are inhibited by l-amino acids and peptides via a means of uncompetitive mechanism. Alkaline phosphatase_sentence_128

These properties noticeably differ between different mammalian alkaline phosphatase isozymes and therefore showcase a difference in in vivo functions. Alkaline phosphatase_sentence_129

Alkaline phosphatase has homology in a large number of other enzymes and composes part of a superfamily of enzymes with several overlapping catalytic aspects and substrate traits. Alkaline phosphatase_sentence_130

This explains why most salient structural features of mammalian alkaline are the way they are and reference their substrate specificity and homology to other members of the nucleoside pyrophosphatase/phosphodiesterase family of isozyme. Alkaline phosphatase_sentence_131

Research has shown a relationship between members of the alkaline phosphatase family with aryl sulfatases. Alkaline phosphatase_sentence_132

The similarities in structure indicate that these two enzyme families came from a common ancestor. Alkaline phosphatase_sentence_133

Further analysis has linked alkaline phosphates and aryl sulfatases to a larger superfamily. Alkaline phosphatase_sentence_134

Some of the common genes found in this superfamily, are ones that encode phosphodiesterases as well as autotoxin. Alkaline phosphatase_sentence_135

See also Alkaline phosphatase_section_15

Alkaline phosphatase_unordered_list_6

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: phosphatase.