Keratan sulfate
Encyclopedia
Keratan sulfate also called keratosulfate, is any of several sulfated
glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea
, cartilage
, and bone
. It is also synthesized in the central nervous system
where it participates both in development
and in the glial scar
formation following an injury. Keratan sulfates are large, highly hydrated molecules which in joints can act as a cushion to absorb mechanical shock
.
s keratan sulfate is a linear polymer
that consists of a repeating disaccharide
unit. Keratan sulfate occurs as a proteoglycan
(PG) in which KS chains are attached to cell-surface or extracellular matrix
proteins, termed core proteins. KS core proteins include Lumican, Keratocan, Mimecan, Fibromodulin, PRELP
, Osteoadherin and Aggrecan
.
The basic repeating disaccharide unit within keratan sulfate is -3Gal
β1-4GlcNAc
β1-. This can be sulfated at carbon position 6 (C6) of either or both the Gal or GlcNAc monosaccharide
s. However, the detailed primary structure
of specific KS types are best considered to be composed of three regions:
The monosaccharide mannose
is found within the linkage region of keratan sulfate type I (KSI). Disaccharides within the repeating region of KSII may be fucosylated
and N-Acetylneuraminic acid
caps the end of all keratan sulfate type II (KSII) chains and up to 70% of KSI type chains.
amino acid
s via N-acetylglucosamine
and KSII is O-linked to specific Serine
or Threonine
amino acids via N-acetyl galactosamine. The tissue based classification of KS no longer exists as KS types have been shown to be non tissue specific. A third type of KS (KSIII) has also been isolated from brain
tissue that is O-linked to specific serine or threonine amino acids via mannose
.
s and is thought to play a role of a dynamic buffer of corneal hydration. In a rare progressive disorder called macular corneal dystrophy
(MCDC), the synthesis of keratan sulfate is either absent (MCDC type I) or abnormal (MCDC type II).
are core proteins found in bone
and cartilage, that are modified by N-linked KS chains.
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
, cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
, and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
. It is also synthesized in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
where it participates both in development
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...
and in the glial scar
Glial scar
Glial scar formation is a reactive cellular process involving astrogliosis that occurs after injury to the Central Nervous System. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system...
formation following an injury. Keratan sulfates are large, highly hydrated molecules which in joints can act as a cushion to absorb mechanical shock
Shock (mechanics)
A mechanical or physical shock is a sudden acceleration or deceleration caused, for example, by impact, drop, kick, earthquake, or explosion. Shock is a transient physical excitation....
.
Keratan sulfate structure
Like other glycosaminoglycanGlycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
s keratan sulfate is a linear polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
that consists of a repeating disaccharide
Disaccharide
A disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water...
unit. Keratan sulfate occurs as a proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
(PG) in which KS chains are attached to cell-surface or extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
proteins, termed core proteins. KS core proteins include Lumican, Keratocan, Mimecan, Fibromodulin, PRELP
PRELP
Prolargin is a protein that in humans is encoded by the PRELP gene.-Further reading:...
, Osteoadherin and Aggrecan
Aggrecan
Aggrecan also known as cartilage-specific proteoglycan core protein or chondroitin sulfate proteoglycan 1 is a protein that in humans is encoded by the ACAN gene. This gene is a member of the aggrecan/versican proteoglycan family...
.
The basic repeating disaccharide unit within keratan sulfate is -3Gal
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
β1-4GlcNAc
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
β1-. This can be sulfated at carbon position 6 (C6) of either or both the Gal or GlcNAc 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...
s. However, the detailed primary structure
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
of specific KS types are best considered to be composed of three regions:
- A linkage region, at one end of which the KS chain is linked to the core protein.
- A repeat region, composed of the -3GalGalactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
β1-4GlcNAcN-AcetylglucosamineN-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
β1- repeating disaccharide unit and - A chain capping region, occurring at the opposite end of the KS chain to the protein linkage region.
The monosaccharide mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
is found within the linkage region of keratan sulfate type I (KSI). Disaccharides within the repeating region of KSII may be fucosylated
Fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on N-linked glycans on the mammalian, insect and plant cell surface, and is the fundamental sub-unit of the fucoidan polysaccharide...
and N-Acetylneuraminic acid
N-Acetylneuraminic acid
N-Acetylneuraminic acid is the predominant sialic acid found in mammalian cells.This negatively charged residue is found in complex glycans on mucins and glycoproteins found at the cell membrane...
caps the end of all keratan sulfate type II (KSII) chains and up to 70% of KSI type chains.
KS classes
The designations KSI and KSII were originally assigned on the basis of the tissue type from which the keratan sulfate was isolated. KSI was isolated from corneal tissue and KSII from skeletal tissue. Minor monosaccharide compositional differences exist between KS extracted from both sources and even KS extracted from the same source. However, major differences occur in the way each KS type is joined to its core protein. The designations KSI and KSII are now based upon these protein linkage differences. KSI is N-linked to specific asparagineAsparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s via N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
and KSII is O-linked to specific Serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
or Threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
amino acids via N-acetyl galactosamine. The tissue based classification of KS no longer exists as KS types have been shown to be non tissue specific. A third type of KS (KSIII) has also been isolated from brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
tissue that is O-linked to specific serine or threonine amino acids via mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
.
Corneal KSI
The amount of KS found in the cornea is 10 fold higher than it is in cartilage and 2-4 times higher than it is in other tissues. It is produced by corneal keratocyteCorneal keratocyte
Corneal keratocytes are specialized fibroblasts residing in the stroma. This corneal layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular matrix components. Keratocytes play the major role in keeping it transparent, healing...
s and is thought to play a role of a dynamic buffer of corneal hydration. In a rare progressive disorder called macular corneal dystrophy
Macular corneal dystrophy
Macular corneal dystrophy is a rare pathological condition affecting the stroma of cornea. The first signs are usually noticed in the first decade of life, and progress afterwards, with opacities developing in the cornea and attacks of pain...
(MCDC), the synthesis of keratan sulfate is either absent (MCDC type I) or abnormal (MCDC type II).
Non-corneal KSI
Osteoadherin, Fibromodulin and PRELPPRELP
Prolargin is a protein that in humans is encoded by the PRELP gene.-Further reading:...
are core proteins found in bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
and cartilage, that are modified by N-linked KS chains.
See also
- N-AcetylglucosamineN-AcetylglucosamineN-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
- galactoseGalactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
- LumicanLUMLumican, also known as LUM, is a protein which in humans is encoded by the LUM gene.- Function :This gene encodes a member of the small leucine-rich proteoglycan family that includes decorin, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin...
- Morquio syndromeMorquio syndromeMorquio's syndrome is an autosomal recessive mucopolysaccharide storage disease , usually inherited. It is a rare type of birth defect with serious consequences...
is marked by the accumulation of KS - Keratan sulfate proteoglycans