Neuropathy target esterase
Encyclopedia
Neuropathy target esterase also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6) is a neuropathy target esterase enzyme
that in humans is encoded by the PNPLA6 gene
.
Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.
activity: It sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine
, which generates water-soluble glycerophosphocholine. In cells of eukaryotes from yeast to humans, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum
membrane and is particularly abundant in neurons, the placenta, and the kidney. Loss of NTE activity results in abnormally elevated levels of phosphatidylcholine in brain and impairment of the constitutive secretory pathway in neurons.
In kidney
, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte
production when a concentrated urine is produced.
Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of hereditary spastic paraplegia
(SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis. Organophosphate-induced delayed neuropathy
a paralysing syndrome with distal degeneration of long axons results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the PNPLA6 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.
Function
Neuropathy target esterase is an enzyme with phospholipase BPhospholipase B
Phospholipase B 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 ....
activity: It sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines 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 soy beans from which they are mechanically extracted or chemically...
, which generates water-soluble glycerophosphocholine. In cells of eukaryotes from yeast to humans, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
membrane and is particularly abundant in neurons, the placenta, and the kidney. Loss of NTE activity results in abnormally elevated levels of phosphatidylcholine in brain and impairment of the constitutive secretory pathway in neurons.
In kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte
Osmolyte
Osmolytes are compounds affecting osmosis. They are soluble in the solution within a cell, or in the surrounding fluid, e.g. as plasma osmolytes. They play a role in maintaining cell volume and fluid balance. For example, when a cell swells due to external osmotic pressure, membrane channels open...
production when a concentrated urine is produced.
Clinical significance
Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is 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
Hereditary Spastic Paraplegia , also called Familial Spastic Paraplegias or Strumpell-Lorrain disease, is a group of inherited diseases whose main feature is progressive stiffness and contraction in the lower limbs. as a result of damage to dysfunction of the nerves...
(SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis. Organophosphate-induced delayed neuropathy
Organophosphate-induced delayed neuropathy
Organophosphate-induced delayed neuropathy , also called organophosphate-induced delayed polyneuropathy , is a neuropathy caused by killing of neurons in the central nervous system, especially in the spinal cord, as a result of acute or chronic organophosphate poisoning.A striking example of OPIDN...
a paralysing syndrome with distal degeneration of long axons results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.