Sodium-glucose transport proteins
Encyclopedia
Sodium-dependent glucose cotransporters (SGLT) are a family of glucose transporter
found in the intestinal mucosa (enterocytes) of the small intestine
(SGLT1) and the proximal tubule
of the nephron
(SGLT2 in PCT and SGLT1 in PST). They contribute to renal glucose reabsorption
. In the kidneys, 100% of the filtered glucose in the glomerulus
has to be reabsorbed along the nephron (98% in PCT, via SGLT2). In case of too high plasma glucose concentration (hyperglycemia
), glucose is excreted in urine (glucosuria); because SGLT are saturated with the filtered monosaccharide
. One must know that glucose is never secreted by the nephron.
Including SGLT1 and SGLT2, there are total seven members in the human protein family SLC5A, several of which may also be sodium-glucose transporters.
cell.
The SGLT proteins use the energy from this downhill sodium gradient created by the ATPase pump to transport glucose
across the apical membrane against an uphill glucose gradient. Therefore, these co-transporters are an example of secondary active transport
. (The GLUT uniporters then transport the glucose across the basolateral membrane, into the peritubular capillaries
.) Both SGLT1 and SGLT2 are known as symporter
s, since both sodium and glucose are transported in the same direction across the membrane.
presented for the first time his discovery of the sodium-glucose cotransport
as the mechanism for intestinal glucose absorption.
Crane
's discovery of cotransport
was the first-ever proposal of flux coupling in biology.
Glucose transporter
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla...
found in the intestinal mucosa (enterocytes) of the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
(SGLT1) and the proximal tubule
Proximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
of the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
(SGLT2 in PCT and SGLT1 in PST). They contribute to renal glucose reabsorption
Renal glucose reabsorption
Renal glucose reabsorption is the part of renal physiology that deals with the retrieval of filtered glucose, preventing it from disappearing from the body through the urine....
. In the kidneys, 100% of the filtered glucose in the glomerulus
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
has to be reabsorbed along the nephron (98% in PCT, via SGLT2). In case of too high plasma glucose concentration (hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
), glucose is excreted in urine (glucosuria); because SGLT are saturated with the filtered monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
. One must know that glucose is never secreted by the nephron.
Types
The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family.| Gene | Protein | Acronym | Tissue distribution in proximal tubule | Na+:Glucose Co-transport ratio | reabsorption (%) | Sodium/GLucose coTransporter 1 |
SGLT1 | S3 segment | 2:1 | >- | Sodium/GLucose coTransporter 2 |
SGLT2 | predominately in the S1 and S2 segments |
1:1 | 90 |
|---|
Including SGLT1 and SGLT2, there are total seven members in the human protein family SLC5A, several of which may also be sodium-glucose transporters.
Function
First, the Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule, cell actively (requires ATP) transports sodium from this cell into the peritubular capillary. This creates a downhill sodium gradient inside the proximal tubuleProximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
cell.
The SGLT proteins use the energy from this downhill sodium gradient created by the ATPase pump to transport glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
across the apical membrane against an uphill glucose gradient. Therefore, these co-transporters are an example of secondary active transport
Secondary active transport
In secondary active transport or co-transport, uses energy to transport molecules across a membrane; however, in contrast to primary active transport, there is no direct coupling of ATP; instead, the electrochemical potential difference created by pumping ions out of the cell is used...
. (The GLUT uniporters then transport the glucose across the basolateral membrane, into the peritubular capillaries
Peritubular capillaries
In the renal system, peritubular capillaries are tiny blood vessels that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron....
.) Both SGLT1 and SGLT2 are known as symporter
Symporter
A cotransporter is an integral membrane protein that is involved in secondary active transport. It works by binding to two molecules or ions at a time and using the gradient of one solute's concentration to force the other molecule or ion against its gradient....
s, since both sodium and glucose are transported in the same direction across the membrane.
Discovery of sodium-glucose cotransport
In August 1960, in Prague, Robert K. CraneRobert K. Crane
Robert Kellogg Crane is an American biochemist best known for his discovery of sodium-glucose cotransport.-Biography:...
presented for the first time his discovery of the sodium-glucose cotransport
Co-transport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
as the mechanism for intestinal glucose absorption.
Crane
Robert K. Crane
Robert Kellogg Crane is an American biochemist best known for his discovery of sodium-glucose cotransport.-Biography:...
's discovery of cotransport
Co-transport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
was the first-ever proposal of flux coupling in biology.
See also
- CotransportCo-transportCo-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
- Cotransporter
- Glucose-galactose malabsorptionGlucose-galactose malabsorptionGlucose-galactose malabsorption is a condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them....
- Renal sodium reabsorptionRenal sodium reabsorptionRenal reabsorption of sodium is a part of renal physiology. It uses Na-H antiport, Na-glucose symport, sodium ion channels . It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide....
- SGLT1
- SGLT2