292932 collagen
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COLLAGENCOLLAGEN
BiochemistryBiochemistry
COLLAGENCOLLAGEN
is the main is the main protein of connective of connective tissue in animals and the most tissue in animals and the most abundant protein in mammals, abundant protein in mammals, making up about 25% of the total making up about 25% of the total protein content protein content
COLLAGENCOLLAGEN
Collagens illustrates diverse Collagens illustrates diverse
structure-function relationshipsstructure-function relationships
Collagen of tendons – forms highly asymmetric structures of high tensile strength
Skin collagen – forms loosely woven, flexible fibers Collagen of hard regions of teeth & bone – contains
hydroxyapatite, a calcium phosphate polymer Collagen in the cornea – nearly crystalline, transparent
COLLAGENCOLLAGEN
Tropocollagen is a Triple Helical moleculeTropocollagen is a Triple Helical molecule
Rich in Gly, Pro, and HypRich in Gly, Pro, and Hyp
TropocollagenTropocollagen- - consist of 3 approximately 1000-residue polypeptide chains organized as left-handed non-α-helix
that has approximately three residues per turn.
Three left-handed helices entwine to form a right-handed
triple helix, or supercoil stabilized by hydrogen bonds
formed between individual polypeptide chains.
COLLAGENCOLLAGEN
TropocollagenTropocollagen
The supercoil resists unwinding because it and its three polypeptides are coiled in opposite directions.
The highly asymmetric mature collagen fibers measures 1.5 nm by about 300 nm, reflecting their stable, extended conformation.
COLLAGENCOLLAGEN
Spatial arrangement of atoms.It can change only by rotating bonds, no bonds are broken.
α chains coiled about each other into a right-handed triple helixes
Every third residue is GlycineEvery third residue is Glycine
(Gly-X-Pro/Hyp)n
The primary structural motif of mature collagen.
Every 3rd residue is Glycine, the only residue with an R group small enough to fit within the central core of the superhelix.
Each Glycine is preceded by either a Prolyl or Hydroxyprolyl residue.
COLLAGENCOLLAGEN
COLLAGENCOLLAGEN
Many Posttranslational modificationsMany Posttranslational modifications
Characterize Procollagen maturationCharacterize Procollagen maturation
Procollagencollagen precursor with the carboxyl and amino terminals have an amino acid
composition typical of a globular protein.
During maturation of procollagen, these carboxyl and amino terminal extensions are removed by selective proteolysis.
Hydroxylation of prolyl and lysyl residues is catalyzed by prolyl hydroxylase and lysyl hyroxylase – enzymes that require ascorbic acid (vit. C)
Specific hydroxylysyl residues are then glycosylated by galactosyl and glucosyl transferases.
Covalent cross-links stabilize collagen fibersCovalent cross-links stabilize collagen fibersTropocollagen associate to form collagen microfibrils.
Stabilized by intrachain hydrogen bonds Covalent bonds formed within & between helices
*This covalent cross-linking process involves the copper-requiring enzyme lysyl oxidase, which converts the non-α-amino groups of hydroxyl residues to aldehydes.
*These aldehydes then either undergo an aldol condensation or condense with the non-α-amino groups of lysine or hydroxylysine, forming Schiff bases.
COLLAGENCOLLAGEN
Nutritional an Genetic disordersNutritional an Genetic disorders
Can involve impaired secondary structureCan involve impaired secondary structure
The medical importance of stable secondary structures is thoroughly documented by disorders of tropocollagen biosynthesis and maturation.
COLLAGENCOLLAGEN
Severe Vitamin C deficiency-prolyl & lysyl hydroxylases are inactive and tropocollagen cannot
undergo the reactions that form covalent cross-links which results to scurvy
SCURVY- nutritional disorder characterized by bleeding gums, poor wound healing, an ultimately death.
Menke’s diseaseis caused by a defective gene that regulates the metabolism of copper in the body. Because it is an X-linked gene, the disease primarily affects male infants. Copper accumulates at abnormally low levels in the liver and brain, but at higher than normal levels in the kidney and intestinal lining. Affected infants may be born prematurely, characterized by kinky hair and growth retardation’
COLLAGENCOLLAGEN
Genetic disorders of collagen biosynthesis include several form of osteogenesis imperfecta characterized by fragile bones.
Ehlers-Danlos syndrome characterized by mobile joints and skin abnormalities, reflect defects in the genes that -encode α1-procollagen, procollagen N-peptidase, or lysyly hydroxylase.
COLLAGENCOLLAGEN
