Alkalinphosphat

3/14/2020 Alkaline phosphatase - Wikipedia
Alkaline phosphatase
Alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos)
Alkaline phosphatase
(EC 3.1.3.1 (https://enzyme.expasy.org/EC/3.1.3.1)), or basic
phosphatase,[2] is a homodimeric protein enzyme of 86
kilodaltons. 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.[3][4]
ALP has the physiological role of dephosphorylating

compounds. The enzyme is found across a multitude of
organisms, prokaryotes and eukaryotes alike, with the same Ribbon diagram (rainbow-color, N-
general function but in different structural forms suitable to the terminus = blue, C-terminus = red) of
environment they function in. Alkaline phosphatase is found in the dimeric structure of bacterial
the periplasmic space of E. coli bacteria. This enzyme is heat alkaline phosphatase.[1]
stable and has its maximum activity at high pH. In humans, it is Identifiers
found in many forms depending on its origin within the body – EC 3.1.3.1 (https://www.qmu
it plays an integral role in metabolism within the liver and number l.ac.uk/sbcs/iubmb/enzy
development within the skeleton. Due to its widespread me/EC3/1/3/1.html)
prevalence in these areas, its concentration in the bloodstream
CAS 9001-78-9 (http://www.co
is used by diagnosticians as a biomarker in helping determine
number mmonchemistry.org/Che
diagnoses such as hepatitis or osteomalacia.[5]
micalDetail.aspx?ref=900
The level of alkaline phosphatase in the blood is checked 1-78-9&title=)
through the ALP test, which is often part of routine blood tests. Databases
The levels of this enzyme in the blood depend on factors such as IntEnz IntEnz view (https://www.
age, sex, blood type.[6] Blood levels of alkaline phosphatase also ebi.ac.uk/intenz/query?c
increase by two to four times during pregnancy. This is a result md=SearchEC&ec=3.1.3.
of additional alkaline phosphatase produced by the placenta.[7] 1)
Additionally, abnormal levels of alkaline phosphatase in the
BRENDA BRENDA entry (http://ww
blood could indicate issues relating to the liver, gall bladder or
w.brenda-enzymes.org/e
bones. Kidney tumors and infections as well as malnutrition
nzyme.php?ecno=3.1.3.
have also shown abnormal level of alkaline phosphatase in
1)
blood.[8] Alkaline phosphatase levels in a cell can be measured
through a process called "The scoring method". This is a ExPASy NiceZyme view (http://ww
technique used where a sample of the enzyme is extracted from w.expasy.org/enzyme/3.
the inside of blood cells and is analyzed and compared for 1.3.1)
varying enzyme activity. A blood smear is usually taken and KEGG KEGG entry (https://www.
undergoes differential centrifugation to isolate leukocytes and genome.jp/dbget-bin/ww
staining to categorize each leukocyte into specific "leukocyte w_bget?enzyme+3.1.3.1)
alkaline phosphatase indices". This marker is designed to MetaCyc metabolic pathway (http
distinguish leukocytes and determine different enzyme activity s://biocyc.org/META/subs
from each sample's extent of staining.[9]
https://en.wikipedia.org/wiki/Alkaline_phosphatase 1/16
tring-search?type=NIL&o
bject=3.1.3.1)
Contents PRIAM profile (http://priam.prabi.f
Bacterial r/cgi-bin/PRIAM_profiles_
CurrentRelease.pl?EC=3.
Use in research
Ongoing research 1.3.1)
Dairy industry PDB RCSB PDB (http://www.rcsb.o
Inhibitors structures rg/pdb/search/smartSubquery.

do?smartSearchSubtype=Enz
Human
ymeClassificationQuery&Enzy
Physiology
Intestinal alkaline phosphatase me_Classification=3.1.3.1)
In cancer cells PDBe (https://www.ebi.ac.uk/p

dbe/entry/search/index?ec_nu
Elevated levels
mber:3.1.3.1) PDBsum (http
Lowered levels
s://www.ebi.ac.uk/thornton-sr
Prognostic uses
Leukocyte alkaline phosphatase v/databases/cgi-bin/enzymes/
GetPage.pl?ec_number=3.1.
Structure and properties
3.1)
See also
Gene AmiGO (http://amigo.geneont
References
Ontology ology.org/amigo/term/GO:000
Further reading 4035) / QuickGO (https://ww
External links w.ebi.ac.uk/QuickGO/term/G
O:0004035)
Search
Bacterial
PMC articles (https://www.ncbi.nlm.
In Gram-negative bacteria, such as Escherichia coli (E. coli), nih.gov/entrez/query.fcgi?db=p
alkaline phosphatase is located in the periplasmic space, ubmed&term=3.1.3.1%5BEC/
RN%20Number%5D%20AN
external to the inner cell membrane and within the
D%20pubmed%20pmc%20loc
peptidoglycan portion of the cell wall. Since the periplasmic gap al%5Bsb%5D)
is more prone to environmental variation than the inner cell,
PubMed articles (https://www.ncbi.nlm.
alkaline phosphatase is suitably resistant to inactivation, nih.gov/entrez/query.fcgi?db=p
denaturation, or degradation. This characteristic of the enzyme ubmed&term=3.1.3.1%5BEC/
is uncommon to many other proteins.[10] RN%20Number%5D)
NCBI proteins (https://www.ncbi.nlm.

The precise structure and function of the four isozymes (Int in nih.gov/protein?term=3.1.3.
E.coli) are solely geared to supply a source of inorganic 1%5BEC/RN%20Number%5
phosphate when the environment lacks this metabolite. The D)
four enzymes are dependent upon the location of the tissue
expression. The four sites of tissue expression are the Intestinal Alkaline phosphatase
AlP, Placental ALP, Germ Cell ALP and Liver/Bone/Kidney
ALP.[11] 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.[12]
While the outer membrane of E. coli contains porins that are

permeable to phosphorylated compounds, the inner membrane
does not. Then, an issue arises in how to transport such
compounds across the inner membrane and into the cytosol.
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. The solution
arises in cleaving the phosphate group away from the
compound via ALP. In effect, along with the concomitant Structure of alkaline phosphatase.[1]
compound the phosphate was bound to, this enzyme yields pure Identifiers
inorganic phosphate which can be ultimately targeted by the Symbol Alk_phosphatase
phosphate-specific transport system (Pst system)[13] for
Pfam PF00245 (http://pfam.xfa
translocation into the cytosol.[14] As such, the main purpose of
m.org/family?acc=PF0024
dephosphorylation by alkaline phosphatase is to increase the
5)
rate of diffusion of the molecules into the cells and inhibit them
from diffusing out.[15] InterPro IPR001952 (https://www.e
bi.ac.uk/interpro/entry/IPR
Alkaline phosphatase is a zinc-containing dimeric enzyme with 001952)
the MW: 86,000 Da, each subunit containing 429 amino acids SMART SM00098 (http://smart.em
with four cysteine residues linking the two subunits.[16] Alkaline bl-heidelberg.de/smart/do_
phosphatase contains four Zn ions and two Mg ions, with Zn annotation.pl?DOMAIN=S
occupying active sites A and B, and Mg occupying site C, so the M00098)
fully active native alkaline phosphatase is referred to as
PROSITE PDOC00113 (http://www.e
(ZnAZnBMgC)2 enzyme. The mechanism of action of alkaline
xpasy.org/cgi-bin/prosite-s
phosphatase involves the geometric coordination of the
earch-ac?PDOC00113)
substrate between the Zn ions in the active sites, whereas the
Mg site doesn't appear to be close enough to directly partake in SCOPe 1alk (https://scop.berkeley.
the hydrolysis mechanism, however, it may contribute to the edu/search/key=1alk) /
shape of the electrostatic potential around the active center.[16] SUPFAM (http://supfam.or
Alkaline phosphatase has a Km of 8.4 x 10−4.[17] g/SUPERFAMILY/cgi-bin/s
earch.cgi?search_field=1al
Alkaline phosphatase in E. coli is uncommonly soluble and k)
active within elevated temperature conditions such as 80 °C. Available protein structures:
Due to the kinetic energy induced by this temperature the weak Pfam structures (http://pfam.xfam.or
hydrogen bonds and hydrophobic interactions of common g/family/PF00245?tab=pdbBl
proteins become degraded and therefore coalesce and ock) / ECOD (http://prodata.s
precipitate. However, upon dimerization of ALP the bonds wmed.edu/ecod/complete/sea
maintaining its secondary and tertiary structures are effectively rch?kw=PF00245)
buried such that they are not affected as much at this PDB RCSB PDB (http://www.rcsb.o
temperature. Furthermore, even at more elevated temperatures rg/pdb/search/smartSubquery.
do?smartSearchSubtype=Pfa
such as 90 °C ALP has the uncommon characteristic of reverse
mIdQuery&pfamID=PF00245);
denaturation. Due to this, while ALP ultimately denatures at PDBe (https://www.ebi.ac.uk/
about 90 °C it has the added ability to accurately reform its pdbe/entry/search/index?pfa
bonds and return to its original structure and function once m_accession:PF00245); PDBj
cooled back down.[10] (https://pdbj.org/searchFor?qu
ery=PF00245)
PDBsum structure summary (https://ww

Alkaline phosphatase in E. coli is located in the periplasmic w.ebi.ac.uk/thornton-srv/datab

space and can thus be released using techniques that weaken ases/cgi-bin/pdbsum/GetPfam
Str.pl?pfam_id=PF00245)
the cell wall and release the protein. Due to the location of the
enzyme, and the protein layout of the enzyme, the enzyme is in PDB 1aja (https://www.rcsb.org/str
ucture/1aja), 1ajb (https://ww
solution with a smaller amount of proteins than there are in
w.rcsb.org/structure/1ajb),
another portion of the cell. [18] The proteins' heat stability can 1ajc (https://www.rcsb.org/stru
also be taken advantage of when isolating this enzyme (through cture/1ajc), 1ajd (https://www.
heat denaturation). In addition, alkaline phosphatase can be rcsb.org/structure/1ajd), 1alh
assayed using p-Nitrophenyl phosphate. A reaction where (https://www.rcsb.org/structur
alkaline phosphatase dephosphorylates the non-specific e/1alh), 1ali (https://www.rcsb.
org/structure/1ali), 1alj (http
substrate, p-Nitrophenyl phosphate in order to produce p-
s://www.rcsb.org/structure/1al
Nitrophenol(PNP) and inorganic phosphate. PNP's yellow color, j), 1alk (https://www.rcsb.org/s
and its λmax at 410 allows spectrophotometry to determine tructure/1alk), ,1anj 1ani ,1anj
important information about enzymatic activity.[19] Some (https://www.rcsb.org/structur
complexities of bacterial regulation and metabolism suggest e/1ani), 1b8j (https://www.rcs
that other, more subtle, purposes for the enzyme may also play b.org/structure/1b8j), 1ed8 (ht
tps://www.rcsb.org/structure/1
a role for the cell. In the laboratory, however, mutant
ed8), 1ed9 (https://www.rcsb.
Escherichia coli lacking alkaline phosphatase survive quite well, org/structure/1ed9), 1elx (http
as do mutants unable to shut off alkaline phosphatase s://www.rcsb.org/structure/1el
production.[20] x), 1ely (https://www.rcsb.org/
structure/1ely), 1elz (https://w
The optimal pH for the activity of the E. coli enzyme is 8.0[21] ww.rcsb.org/structure/1elz),
while the bovine enzyme optimum pH is slightly higher at ,1ew8 1ew2 ,1ew8 (https://ww
w.rcsb.org/structure/1ew2),
8.5.[22] Alkaline phosphatase accounts for 6% of all proteins in
1ew9 (https://www.rcsb.org/str
derepressed cells.[17] ucture/1ew9), 1hjk (https://ww
w.rcsb.org/structure/1hjk),
Use in research 1hqa (https://www.rcsb.org/str
ucture/1hqa), 1k7h (https://ww
By changing the amino acids of the wild-type alkaline w.rcsb.org/structure/1k7h),
phosphatase enzyme produced by Escherichia coli, a mutant 1kh4 (https://www.rcsb.org/str
ucture/1kh4), 1kh5 (https://ww
alkaline phosphatase is created which not only has a 36-fold
w.rcsb.org/structure/1kh5),
increase in enzyme activity, but also retains thermal ,1kh9 1kh7 ,1kh9 (https://ww
stability.[23] Typical uses in the lab for alkaline phosphatases w.rcsb.org/structure/1kh7),
include removing phosphate monoesters to prevent self- 1khj (https://www.rcsb.org/stru
ligation, which is undesirable during plasmid DNA cloning.[24] cture/1khj), 1khk (https://www.
rcsb.org/structure/1khk), 1khl
Common alkaline phosphatases used in research include: (https://www.rcsb.org/structur
e/1khl), 1khn (https://www.rcs
Shrimp alkaline phosphatase (SAP), from a species of Arctic b.org/structure/1khn), 1shn (ht
shrimp (Pandalus borealis). This phosphatase is easily tps://www.rcsb.org/structure/1
inactivated by heat, a useful feature in some applications. shn), 1shq (https://www.rcsb.o
rg/structure/1shq), ,1urb 1ura
Calf-intestinal alkaline phosphatase (CIP)
,1urb (https://www.rcsb.org/str
Placental alkaline phosphatase (PLAP) and its C terminally ucture/1ura), 1y6v (https://ww
truncated version that lacks the last 24 amino acids w.rcsb.org/structure/1y6v),
(constituting the domain that targets for GPI membrane 1y7a (https://www.rcsb.org/str
anchoring) – the secreted alkaline phosphatase (SEAP). It ucture/1y7a), 1zeb (https://ww
presents certain characteristics like heat stability, substrate w.rcsb.org/structure/1zeb),
specificity, and resistance to chemical inactivation.[25] 1zed (https://www.rcsb.org/str
Human-intestinal alkaline phosphatase. The human body ucture/1zed), 1zef (https://ww

has multiple types of alkaline phosphatase present, which w.rcsb.org/structure/1zef),
are determined by a minimum of three gene loci. Each one 2anh (https://www.rcsb.org/str
of these three loci controls a different kind of alkaline ucture/2anh), ,2ga3 2g9y
phosphatase isozyme. However, the development of this ,2ga3 (https://www.rcsb.org/st
enzyme can be strictly regulated by other factors such as ructure/2g9y), 2glq (https://ww
thermostability, electrophoresis, inhibition, or w.rcsb.org/structure/2glq)
immunology.[26]
Human-intestinal ALPase shows around 80% homology with bovine intestinal ALPase, which holds
true their shared evolutionary origins. That same bovine enzyme has more than 70% homology with
human placental enzyme. However, the human intestinal enzyme and the placental enzyme only
share 20% homology despite their structural similarities.[27]
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), 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.
Because 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).[28]
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.[29]
Ongoing research
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.[30]
Alkaline phosphatase (AP) affects the inflammatory responses in patients with Chronic kidney
disease and is directly associated with Erythropoiesis stimulating agent resistant anemia.[31]
Intestinal alkaline phosphatase (IAP) and the mechanism it uses to regulate pH and ATP
hydrolysis in rat duodenum.[32]
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."[33]
Dairy industry
Alkaline phosphatase is commonly used in the dairy industry as an indicator of successful

pasteurization. This is because the most heat stable bacterium found in milk, Mycobacterium
paratuberculosis, is destroyed by temperatures lower than those required to denature ALP.
Therefore, ALP presence is ideal for indicating failed pasteurization.[34][35]
Pasteurization verification is typically performed by measuring the fluorescence of a solution which

becomes fluorescent when exposed to active ALP. Fluorimetry assays are required by milk producers
in the UK to prove alkaline phosphatase has been denatured,[36] as p-Nitrophenylphosphate tests are
not considered accurate enough to meet health standards.
Alternatively the colour change of a para-Nitrophenylphosphate substrate in a buffered solution

(Aschaffenburg Mullen Test) can be used.[37] Raw milk would typically produce a yellow colouration
within a couple of minutes, whereas properly pasteurised milk should show no change. 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.
Inhibitors
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.[38] Phosphate is another inhibitor which competitively inhibits alkaline phosphatase.[39]
Another known example of an alkaline phosphatase inhibitor is [(4-Nitrophenyl)methyl]phosphonic

acid.[40]
In metal contaminated soil, alkaline phosphatase are inhibited by Cd (Cadmium). In addition,

temperature enhances the inhibition of Cd on ALP activity, which is shown in the increasing values of
Km.[41]
Human
Physiology
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. In the serum, two
types of alkaline phosphatase isozymes predominate: skeletal and liver. During childhood the
majority of alkaline phosphatase are of skeletal origin.[42] Humans and most other mammals contain
the following alkaline phosphatase isozymes:
ALPI – intestinal (molecular weight of 150 kDa)

ALPL – tissue-nonspecific (expressed mainly in liver, bone, and kidney)
ALPP – placental (Regan isozyme)
GCAP – germ cell
Four genes encode the four isozymes. 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.[4]
Intestinal alkaline phosphatase

Intestinal alkaline phosphatase is secreted by enterocytes, and seems to play a pivotal role in
intestinal homeostasis and protection[43][44] as well as in mediation of inflammation[45] via
repression of the downstream Toll-like receptor (TLR)-4-dependent and MyD88-dependent
inflammatory cascade. It dephosphorylates toxic/inflammatory microbial ligands like
lipopolysaccharides, unmethylated cytosine-guanine dinucleotides, flagellin, and extracellular
nucleotides such as uridine diphosphate or ATP. Thus, altered IAP expression has been implicated in
chronic inflammatory diseases such as inflammatory bowel disease (IBD).[46][47] It also seems to
regulate lipid absorption[48] and bicarbonate secretion[49] in the duodenal mucosa, which regulates
the surface pH.
In cancer cells
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. One study
compared the enzymes of liver metastases of giant-cell lung carcinoma and nonmalignant placental
cells. The two were similar in NH2-terminal sequence, peptide map, subunit molecular weight, and
isoelectronic point.[50]
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. However, this study revealed that without the influence of
sodium butyrate, alkaline phosphatase activity is fairly low in cancer cells.[51] 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.[52] This explains why
the addition of sodium butyrate show increased activity of alkaline phosphatase in the cancer cells of
the human colon.[51] In addition, this further supports the theory that alkaline phosphatase enzyme
activity is actually present in cancer cells.
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. This
procedure of enhancing the activity of the enzyme is known as enzyme induction. The evidence shows
that there is in fact activity of alkaline phosphatase in tumor cells, but it is minimal and needs to be
enhanced. 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.[53][54] but 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.[55]
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.[56] Lowered levels of ALP are less
common than elevated levels. The source of elevated ALP levels can be deduced by obtaining serum
levels of gamma glutamyltransferase (GGT). Concomitant increases of ALP with GGT should raise the
suspicion of hepatobiliary disease.[57]
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.[58]
Elevated levels
If it is unclear why alkaline phosphatase is elevated, isoenzyme studies using electrophoresis can
confirm the source of the ALP. Skelphosphatase (which is localized in osteoblasts and extracellular
layers of newly synthesized matrix) is released into circulation by a yet unclear mechanism.[59]
Placental alkaline phosphatase is elevated in seminomas[60] and active forms of rickets, as well as in
the following diseases and conditions:[61]
Biliary obstruction
Bone conditions
Osteoblastic bone tumors
Osteomalacia
Osteoporosis[62]
Hepatitis
Cirrhosis
Acute cholecystitis
Myelofibrosis
Leukemoid reaction
Lymphoma
Paget's disease
Sarcoidosis
Hyperthyroidism
Hyperparathyroidism
Myocardial infarction
Pregnancy
Lowered 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 aging
Men with recent heart surgery, malnutrition, magnesium deficiency, or severe anemia
Children with achondroplasia and congenital iodine deficiency
Children after a severe episode of enteritis
Pernicious anemia
Aplastic anemia
Wilson's disease
Hypothyroidism
In addition, oral contraceptives have been demonstrated to reduce alkaline phosphatase.[63]
Prognostic uses
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.[64]
Leukocyte alkaline phosphatase

Leukocyte alkaline phosphatase (LAP) is found within mature white blood cells. White blood cell
levels of LAP can help in the diagnosis of certain conditions.
Higher 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).
Structure and properties

Alkaline phosphatase is homodimeric enzyme, meaning it is formed with two molecules. Three metal
ions, two Zn and one Mg, are contained in the catalytic sites, and both types are crucial for enzymatic
activity to occur. The enzymes catalyze the hydrolysis of monoesters in phosphoric acid which can
additionally catalyze a transphosphorylation reaction with large concentrations of phosphate
acceptors. While the main features of the catalytic mechanism and activity are conserved between
mammalian and bacterial alkaline phosphate, mammalian alkaline phosphatase has higher a 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. These properties noticeably differ between different mammalian alkaline
phosphatase isozymes and therefore showcase a difference in in vivo functions.
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. 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
[4]
pyrophosphatase/phosphodiesterase family of isozyme. Research has shown a relationship between
members of the alkaline phosphatase family with aryl sulfatases. The similarities in structure indicate
that these two enzyme families came from a common ancestor. Further analysis has linked alkaline
phosphates and aryl sulfatases to a larger superfamily. Some of the common genes found in this
superfamily, are ones that encode phosphodiesterases as well as autotoxin.[66]
See also
Acid phosphatase
Liver function tests
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Further reading
Coleman JE (1992). "Structure and mechanism of alkaline phosphatase" (https://semanticscholar.
org/paper/16aaafe74d32f1d33ab121fb49161438b6e12d7e). Annual Review of Biophysics and
Biomolecular Structure. 21: 441–83. doi:10.1146/annurev.bb.21.060192.002301 (https://doi.org/1
0.1146%2Fannurev.bb.21.060192.002301). PMID 1525473 (https://pubmed.ncbi.nlm.nih.gov/1525
473).
External links
Alkaline phosphatase at Lab Tests Online (http://labtestsonline.org/understanding/analytes/alp/ta

b/test)
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3/14/2020 Alkaline phosphatase - Wikipedia

ALP has the physiological role of dephosphorylating

Dairy industry PDB RCSB PDB (http://www.rcsb.o

Inhibitors structures rg/pdb/search/smartSubquery.

In cancer cells PDBe (https://www.ebi.ac.uk/p

NCBI proteins (https://www.ncbi.nlm.

While the outer membrane of E. coli contains porins that are

PDBsum structure summary (https://ww

Alkaline phosphatase in E. coli is located in the periplasmic w.ebi.ac.uk/thornton-srv/datab

Human-intestinal alkaline phosphatase. The human body ucture/1zed), 1zef (https://ww

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

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

Pasteurization verification is typically performed by measuring the fluorescence of a solution which

Alternatively the colour change of a para-Nitrophenylphosphate substrate in a buffered solution

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

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

ALPI – intestinal (molecular weight of 150 kDa)

Intestinal alkaline phosphatase

In another study, choriocarcinoma cells were grown in the presence of 5-bromo-2’-deoxyuridine

Hypophosphatasia, an autosomal recessive disease

Leukocyte alkaline phosphatase

Structure and properties

46. Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M, Mach T,

57. Vroon D (1990). "Alkaline Phosphatase and Gamma Glutamyltransferase" (https://www.ncbi.nlm.n

Alkaline phosphatase at Lab Tests Online (http://labtestsonline.org/understanding/analytes/alp/ta

Retrieved from "https://en.wikipedia.org/w/index.php?title=Alkaline_phosphatase&oldid=943806680"

This page was last edited on 4 March 2020, at 00:56 (UTC).

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