Alkaline phosphatase

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Alkaline phosphatase
1ALK.png
Ribbon diagram (rainbow-color, N-terminus = blue, C-terminus = red) of the dimeric structure of bacterial alkaline phosphatase. [1]
Identifiers
EC no. 3.1.3.1
CAS no. 9001-78-9
Alt. namesalkaline phosphomonoesterase, alkaline phosphatase, alkaline phosphohydrolase, alkaline phenyl phosphatase
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins
Alkaline phosphatase
PDB 1alk EBI.jpg
Structure of alkaline phosphatase. [1]
Identifiers
SymbolAlk_phosphatase
Pfam PF00245
InterPro IPR001952
SMART SM00098
PROSITE PDOC00113
SCOP2 1alk / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1aja ​, 1ajb ​, 1ajc ​, 1ajd ​, 1alh ​, 1ali ​, 1alj ​, 1alk ​, ,1anj 1ani ,1anj ​, 1b8j ​, 1ed8 ​, 1ed9 ​, 1elx ​, 1ely ​, 1elz ​, ,1ew8 1ew2 ,1ew8 ​, 1ew9 ​, 1hjk ​, 1hqa ​, 1k7h ​, 1kh4 ​, 1kh5 ​, ,1kh9 1kh7 ,1kh9 ​, 1khj ​, 1khk ​, 1khl ​, 1khn ​, 1shn ​, 1shq ​, ,1urb 1ura ,1urb ​, 1y6v ​, 1y7a ​, 1zeb ​, 1zed ​, 1zef ​, 2anh ​, ,2ga3 2g9y ,2ga3 ​, 2glq ​

The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase) is a phosphatase with the physiological role of dephosphorylating compounds. 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 is found in the periplasmic space of E. coli bacteria. This enzyme is heat stable and has its maximum activity at high pH. 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. 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. [2]

Contents

The level of alkaline phosphatase in the blood is checked through the ALP test, which is often part of routine blood tests. The levels of this enzyme in the blood depend on factors such as age, sex, or blood type. [2] Blood levels of alkaline phosphatase also increase by two to four times during pregnancy. This is a result of additional alkaline phosphatase produced by the placenta and the liver. [3] [4] Additionally, abnormal levels of alkaline phosphatase in the blood could indicate issues relating to the liver, gall bladder or bones. Kidney tumors and infections as well as malnutrition have also shown abnormal level of alkaline phosphatase in blood. [2] Alkaline phosphatase levels in a cell can be measured through a process called "The scoring method". A blood smear is usually taken and stained to categorize each leukocyte into specific "leukocyte alkaline phosphatase indices". This marker is designed to distinguish leukocytes and determine different enzyme activity from each sample's extent of staining. [5]

Bacterial

In gram-negative bacteria, such as Escherichia coli , alkaline phosphatase is located in the periplasmic space, external to the inner cell membrane and within the peptidoglycan portion of the cell wall. Since the periplasmic gap is more prone to environmental variation than the inner cell, alkaline phosphatase is suitably resistant to inactivation, denaturation, or degradation. This characteristic of the enzyme is uncommon to many other proteins. [6]

The precise structure and function of the isozyme in E. coli is solely geared to supply a source of inorganic phosphate when the environment lacks this metabolite. The inorganic phosphates are then bound to carrier proteins which deliver the inorganic phosphates to a specific high-affinity transport system, known as the phosphate-specific transport system, which transports phosphate across the cytoplasmic membrane. [7]

While the outer membrane of E. coli contains porins that are permeable to phosphorylated compounds, the inner membrane does not. An issue arises in how to transport such compounds across the inner membrane and into the cytosol. The strong anionic charge of phosphate groups along with the remainder of the compound make phosphorylated compounds very much immiscible in the nonpolar region of the bilayer. The solution arises in cleaving the phosphate group away from the compound via ALP. [8] for translocation into the cytosol, [9] The main purpose of dephosphorylation by alkaline phosphatase is to increase the rate of diffusion of phosphorylated molecules into the cells while inhibiting them from diffusing out. [10]

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. [11]  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. The mechanism of action of alkaline phosphatase involves the geometric coordination of the substrate between the Zn ions in the active sites. [11]

Alkaline phosphatase in E. coli is uncommonly soluble and active within elevated temperature conditions such as 80 °C. 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. However, upon dimerization of alkaline phosphatase, the bonds maintaining its secondary and tertiary structures are effectively buried such that they are not affected as much at this temperature. Furthermore, even at more elevated temperatures such as 90 °C alkaline phosphatase has the unusual characteristic of reverse denaturation. Due to this, although it 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. [6]

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. 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. [12] The proteins' heat stability can also be taken advantage of when isolating this enzyme (through heat denaturation). In addition, alkaline phosphatase can be assayed using p-nitrophenyl phosphate. A reaction where alkaline phosphatase dephosphorylates the non-specific substrate, p-nitrophenyl phosphate in order to produce p-nitrophenol (PNP) and inorganic phosphate. PNP's yellow color, and its λmax at 410 allows spectrophotometry to determine enzymatic activity. [13] 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. [14]

The optimal pH for the activity of the E. coli enzyme is 8.0 [15] while the bovine enzyme optimum pH is slightly higher at 8.5. [16] Alkaline phosphatase accounts for 6% of all proteins in derepressed cells. [17]

Intragenic complementation

When multiple copies of a polypeptide encoded by a gene form an aggregate, this protein structure is referred to as a multimer. 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. In such a case, the phenomenon is referred to as intragenic complementation. E. coli alkaline phosphatase, a dimer enzyme, exhibits intragenic complementation. [18]

Use in research

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. [19] Typical uses in the lab for alkaline phosphatases include removing phosphate monoesters to prevent self-ligation, which is undesirable during plasmid DNA cloning. [20]

Common alkaline phosphatases used in research include:

Human-intestinal alkaline phosphatase shows around 80% homology with the bovine intestinal enzyme which holds true their shared evolutionary origins. That same bovine enzyme has more than 70% homology with human placental enzyme. However, the human liver enzyme and the placental enzyme only share 20% homology despite their structural similarities. [23]

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.[ citation needed ]

Another important use of alkaline phosphatase is as a label for enzyme immunoassays.[ citation needed ]

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). [24]

There is a positive correlation between serum bone alkaline phosphatase levels and bone formation in humans, although its use as a biomarker in clinical practice is not recommended. [25]

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 the enzyme. Therefore, its presence is ideal for indicating failed pasteurization. [26] [27]

Pasteurization verification is typically performed by measuring the fluorescence of a solution which becomes fluorescent when exposed to active alkaline phosphatase. Fluorimetry assays are required by milk producers in the UK to prove alkaline phosphatase has been denatured, [28] as p-Nitrophenylphosphate tests are not considered accurate enough to meet health standards.

Alternatively the colour change of p-nitrophenylphosphate as substrate in a buffered solution (Aschaffenburg Mullen Test) can be used. [29] Raw milk would typically produce a yellow coloration 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 phosphatases produced by some bacteria, but these bacteria should not be present in milk.[ citation needed ]

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. [30] Phosphate is another inhibitor which competitively inhibits alkaline phosphatase. [31]

Another known example of an alkaline phosphatase inhibitor is [(4-Nitrophenyl)methyl]phosphonic acid. [32]

In metal contaminated soil, alkaline phosphatase are inhibited by Cd (Cadmium). In addition, temperature enhances the inhibition of Cd on the enzyme activity, which is shown in the increasing values of Km. [33]

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. [34] Humans and most other mammals contain the following alkaline phosphatase isozymes:[ citation needed ]

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. [35]

Intestinal alkaline phosphatase

Intestinal alkaline phosphatase is secreted by enterocytes, and seems to play a pivotal role in intestinal homeostasis and protection [36] [37] as well as in suppressing inflammation [38] via repression of the downstream Toll-like receptor (TLR)-4-dependent and MyD88-dependent inflammatory cascade. [39] It dephosphorylates toxic/inflammatory microbial ligands like lipopolysaccharides (LPSs), [40] unmethylated cytosine-guanine dinucleotides, flagellin, and extracellular nucleotides such as uridine diphosphate or ATP. Dephosphorylation of LPS by IAP can reduce the severity of Salmonella tryphimurium and Clostridioides difficile infection restoring normal gut microbiota. [40] Thus, altered IAP expression has been implicated in chronic inflammatory diseases such as inflammatory bowel disease (IBD). [40] [41] It also seems to regulate lipid absorption [42] and bicarbonate secretion [43] in the duodenal mucosa, which regulates the surface pH. Since the 1960s intestinal alkaline phosphatase has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. [44] The solubility of many drugs can be substantially improved by the design of phosphate prodrugs. On the intestinal mucosa the phosphate substructures are cleaved off by alkaline phosphatase and the drug is absorbed. [45] Furthermore, anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the intestinal epithelium as due to an alkaline phosphatase triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. [46]

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. [47]

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. [48] 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. [49] This explains why the addition of sodium butyrate show increased activity of alkaline phosphatase in the cancer cells of the human colon. [48] In addition, this further supports the theory that alkaline phosphatase enzyme activity is actually present in cancer cells.[ citation needed ]

In another study, choriocarcinoma cells were grown in the presence of 5-bromo-2'-deoxyuridine 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. [50] [51] 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 alkaline phosphatase levels can occur if the bile ducts are obstructed. [52]

Also, the level of alkaline phosphatase increases if there is active bone formation occurring, as the enzyme is a byproduct of osteoblast activity (such as the case in Paget's disease of bone).[ citation needed ]

The level of alkaline phosphatase is much more elevated in metastatic prostate cancer cells than non-metastatic prostate cancer cells. [53] High levels of ALP in prostate cancer patients is associated with a significant decrease in survival. [53]

Levels are also elevated in people with untreated coeliac disease. [54] Lowered levels of the level of alkaline phosphatase are less common than elevated levels. The source of elevated levels can be deduced by obtaining serum levels of γ-glutamyltransferase. Concomitant increases of alkaline phosphatase with γ-glutamyltransferase should raise the suspicion of hepatobiliary disease. [55]

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. [56]

Elevated levels

As of 2020, normal ALP levels were "not well defined", and there tend to be variations by sex and racial background, [57] and by age, with children and adolescents having markedly higher levels. [58]

There are many possible explanations for elevated ALP. When the cause is unclear, isoenzyme studies using electrophoresis can confirm the source of the increase. 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]

Lowered levels

The following conditions or diseases may lead to reduced levels of alkaline phosphatase: [65]

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. [67]

Leukocyte alkaline phosphatase

Leukocyte alkaline phosphatase is found within mature white blood cells. White blood cell levels of LAP can help in the diagnosis of certain conditions.[ citation needed ]

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 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. These properties noticeably differ between different mammalian alkaline phosphatase isozymes and therefore showcase a difference in in vivo  functions.[ citation needed ]

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 pyrophosphatase/phosphodiesterase family of isozyme. [35] 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. [69]

See also

Related Research Articles

Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.

Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is an ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

<span class="mw-page-title-main">Phosphofructokinase 1</span> Class of enzymes

Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell's energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin.

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

<span class="mw-page-title-main">Aldolase A</span> Mammalian protein found in Homo sapiens

Aldolase A, also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ALDOA gene on chromosome 16.

<span class="mw-page-title-main">Phosphofructokinase 2</span> Class of enzymes

Phosphofructokinase-2 (6-phosphofructo-2-kinase, PFK-2) or fructose bisphosphatase-2 (FBPase-2), is an enzyme indirectly responsible for regulating the rates of glycolysis and gluconeogenesis in cells. It catalyzes formation and degradation of a significant allosteric regulator, fructose-2,6-bisphosphate (Fru-2,6-P2) from substrate fructose-6-phosphate. Fru-2,6-P2 contributes to the rate-determining step of glycolysis as it activates enzyme phosphofructokinase 1 in the glycolysis pathway, and inhibits fructose-1,6-bisphosphatase 1 in gluconeogenesis. Since Fru-2,6-P2 differentially regulates glycolysis and gluconeogenesis, it can act as a key signal to switch between the opposing pathways. Because PFK-2 produces Fru-2,6-P2 in response to hormonal signaling, metabolism can be more sensitively and efficiently controlled to align with the organism's glycolytic needs. This enzyme participates in fructose and mannose metabolism. The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate.

<span class="mw-page-title-main">Glycogen synthase</span> Enzyme class, includes all types of glycogen/starch synthases

Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.

<span class="mw-page-title-main">Glucose 6-phosphatase</span> Enzyme

The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose:

<span class="mw-page-title-main">Phosphoglycerate mutase</span> Class of enzymes

Phosphoglycerate mutase (PGM) is any enzyme that catalyzes step 8 of glycolysis - the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) through a 2,3-bisphosphoglycerate intermediate. These enzymes are categorized into the two distinct classes of either cofactor-dependent (dPGM) or cofactor-independent (iPGM). The dPGM enzyme is composed of approximately 250 amino acids and is found in all vertebrates as well as in some invertebrates, fungi, and bacteria. The iPGM class is found in all plants and algae as well as in some invertebrate, fungi, and Gram-positive bacteria. This class of PGM enzyme shares the same superfamily as alkaline phosphatase.

<span class="mw-page-title-main">5'-nucleotidase</span> InterPro Family

5′-Nucleotidase is an enzyme which catalyzes the phosphorylytic cleavage of 5′-nucleotides. Although originally found in snake venom, the activity of 5'nucleotidase has been described for bacteria and plant cells, and is widely distributed in vertebrate tissue. In mammalian cells the enzyme is predominantly located in the plasma membrane and its primary role is in the conversion of extracellular nucleotides, which are generally impermeable, to the corresponding nucleoside which can readily enter most cells. Consequently, the enzyme plays a key role in the metabolism of nucleotides.

<span class="mw-page-title-main">UTP—glucose-1-phosphate uridylyltransferase</span> Class of enzymes

UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,

<span class="mw-page-title-main">Serine dehydratase</span>

Serine dehydratase or L-serine ammonia lyase (SDH) is in the β-family of pyridoxal phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structure and properties vary among species. SDH is found in yeast, bacteria, and the cytoplasm of mammalian hepatocytes. SDH catalyzes the deamination of L-serine to yield pyruvate, with the release of ammonia.

<span class="mw-page-title-main">ACP1</span> Protein-coding gene in humans

Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ACP1 gene.

<span class="mw-page-title-main">ALPL</span> Protein-coding gene in the species Homo sapiens

Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ALPL gene.

<span class="mw-page-title-main">PPAP2A</span> Protein-coding gene in the species Homo sapiens

Lipid phosphate phosphohydrolase 1 also known as phosphatidic acid phosphatase 2a is an enzyme that in humans is encoded by the PPAP2A gene.

<span class="mw-page-title-main">Alkaline phosphatase, placental type</span> Protein-coding gene in the species Homo sapiens

Alkaline phosphatase, placental type also known as placental alkaline phosphatase (PLAP) is an allosteric enzyme that in humans is encoded by the ALPP gene.

<span class="mw-page-title-main">ALPI</span> Protein-coding gene in the species Homo sapiens

Alkaline phosphatase, intestinal also known as ALPI is a type of alkaline phosphatase that in humans is encoded by the ALPI gene.

<span class="mw-page-title-main">Elevated alkaline phosphatase</span> Medical condition

Elevated alkaline phosphatase occurs when levels of alkaline phosphatase (ALP) exceed the reference range. This group of enzymes has a low substrate specificity and catalyzes the hydrolysis of phosphate esters in a basic environment. The major function of alkaline phosphatase is transporting chemicals across cell membranes. Alkaline phosphatases are present in many human tissues, including bone, intestine, kidney, liver, placenta and white blood cells. Damage to these tissues causes the release of ALP into the bloodstream. Elevated levels can be detected through a blood test. Elevated alkaline phosphate is associated with certain medical conditions or syndromes. It serves as a significant indicator for certain medical conditions, diseases and syndromes.

<span class="mw-page-title-main">ALPPL2</span> Protein-coding gene in the species Homo sapiens

Alkaline phosphatase, placental-like 2 is a protein that in humans is encoded by the ALPPL2 gene.

<span class="mw-page-title-main">Lysophosphatidic acid phosphatase type 6</span> Protein-coding gene in the species Homo sapiens

Lysophosphatidic acid phosphatase type 6 is an acid phosphatase enzyme that is encoded in humans by the ACP6 gene.

References

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