Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an
esterase
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.
A wide range of different esterases exist that differ in their substrate specificity, their protein structure, ...
enzyme that in humans is encoded by the ''PNPLA6''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Neuropathy target esterase is a
phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in ...
that deacetylates intracellular
phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
to produce
glycerophosphocholine. It is thought to function in
neurite outgrowth
A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...
and process elongation during
neuronal differentiation. The protein is anchored to the cytoplasmic face of the
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
in both neurons and non-neuronal cells.
Function
Neuropathy target esterase is an enzyme with
phospholipase B
Phospholipase B, also known as lysophospholipase, is an enzyme with a combination of both PLA1 and PLA2 activities; that is, it can cleave acyl chains from both the sn-1 and sn-2 positions of a phospholipid. In general, it acts on lysolecithin (whi ...
activity: it sequentially hydrolyses both fatty acids from the major membrane lipid
phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
, generating water-soluble glycerophosphocholine.
In
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s, it is particularly abundant in neurons, the
placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
, and the kidney.
Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the
constitutive secretory pathway in neurons.
In the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
, the expression of neuropathy target esterase is regulated by
TonEBP as part of
osmolyte
Osmolytes are low-molecular weight organic compounds that influence the properties of biological fluids. Their primary role is to maintain the integrity of cells by affecting the viscosity, melting point, and ionic strength of the aqueous solution. ...
production when the kidney produces concentrated
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
.
Clinical significance
Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.
Recessively-inherited mutations in ''NTE'' that substantially reduce its catalytic activity cause a rare form of
hereditary spastic paraplegia
Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditar ...
(SPG39), in which distal parts of long spinal
axons
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, th ...
degenerate leading to limb weakness and paralysis.
Organophosphate-induced delayed neuropathy
Organophosphate-induced delayed neuropathy (OPIDN), also called organophosphate-induced delayed polyneuropathy (OPIDP), is a neuropathy caused by killing of neurons in the central nervous system, especially in the spinal cord, as a result of acute ...
a paralysing syndrome with distal degeneration of long axons results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.
References
Further reading
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{{NLM content
EC 3.1.1
Enzymes