A urea transporter is a
membrane transport protein
A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral membrane proteins, integral transmembr ...
, transporting
urea
Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...
. Humans and other mammals have two types of urea transport proteins, UT-A and UT-B. The UT-A proteins are important for
renal urea handling Renal urea handling is the part of renal physiology that deals with the reabsorption and secretion of urea. Movement of large amounts of urea across cell membranes is made possible by urea transporter proteins.
Urea allows the kidneys to create h ...
and are produced by alternative splicing of the
SLC14A2
Urea transporter 2 is a protein that in humans is encoded by the ''SLC14A2'' gene.
Function
In mammalian cells, urea is the chief end-product of nitrogen catabolism and plays an important role in the urinary concentration mechanism. Thus, the ...
gene.
Urea transport in the kidney is regulated by
vasopressin
Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the ''AVP'' gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It ...
.
The structure of a urea transport family protein from ''
Desulfovibrio vulgaris
''Nitratidesulfovibrio vulgaris'' (formerly ''Desulfovibrio vulgaris'') is a species of Gram-negative sulfate-reducing bacteria in the Desulfovibrionaceae family. It is also an anaerobic sulfate-reducing bacterium that is an important organism ...
'' was determined by
x-ray crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
.
The structure has a pathway through the membrane that is similar to that of
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
proteins, accounting for the ability of urea transport proteins to move up to one million urea molecules per second across the membrane.
Urea transporters can be inhibited by the action of urea analogues like
thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...
and glycosides like
phloretin
Phloretin is a dihydrochalcone, a type of natural phenol. It can be found in apple tree leaves and the Manchurian apricot.
Metabolism
In rats, ingested phlorizin is converted into phloretin by hydrolytic enzymes in the small intestine. Ph ...
.
Their inhibition results in increased diuresis due to urea induced osmosis in the collecting ducts of the
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
.
Types
In mammals, there are two urea transporter
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s: UT-A (''
SLC14A2
Urea transporter 2 is a protein that in humans is encoded by the ''SLC14A2'' gene.
Function
In mammalian cells, urea is the chief end-product of nitrogen catabolism and plays an important role in the urinary concentration mechanism. Thus, the ...
'') and UT-B (''
SLC14A1''). Multiple
protein isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
s derived from each gene are produced by
alternative splicing
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
and alternative
promoters.
UT-A1
Urea transporter A1 transports urea across the
apical membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...
into the
intracellular space
Intracellular space is the interior space of the plasma membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and prote ...
of luminal cells in the
inner medullary collecting duct
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through rea ...
of the
kidneys
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
. UT-1 is activated by
ADH, but is a passive transporter. It reabsorbs up to 70% of the original filtered load of urea.
UT-A2
Urea Transporter 2 transports urea across the
apical membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...
into the luminal space of cells in the
thin descending loop of Henle
Thin may refer to:
* ''Thin'' (film), a 2006 documentary about eating disorders
* Thin, a web server based on Mongrel
* Thin (name), including a list of people with the name
* Mal language, also known as Thin
See also
*
*
* Body shape
* Emac ...
of the
kidneys
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...
.
UT-A3
Urea transporter 3 transports urea into the interstitium of the Inner Medullary Collecting Duct.
UT-A4
Urea transporter 4 has been detected in rat but not mouse kidney medulla.
UT-A5
Urea transporter 5 is not expressed in the kidney but in the testis.
UT-B
UT-B is widely expressed and has been studied in
erythrocyte
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
s,
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
,
intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
,
and at the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
.
The
SLC14A1 gene codes for the UT-B protein. UT-B is expressed at the basolateral and apical regions of the descending
Vasa recta.
References
{{Membrane transport proteins, bg, bg1
Transmembrane transporters
Renal physiology
Solute carrier family