www.Examville.com Online practice tests, live classes, tutoring, study guides Q&A, premium content and more .
is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% of the total protein content
Collagens illustrates diverse
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
Tropocollagen is a Triple Helical molecule
Rich in Gly, Pro, and Hyp
Tropocollagen - 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.
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.
COLLAGEN 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 Glycine
The primary structural motif of mature collagen.
Every 3 rd 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.
Many Posttranslational modifications
Characterize Procollagen maturation
collagen 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 fibers
Tropocollagen associate to form collagen microfibrils.
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.
Nutritional an Genetic disorders
Can involve impaired secondary structure
The medical importance of stable secondary structures is thoroughly documented by disorders of tropocollagen biosynthesis and maturation.
Severe Vitamin C deficiency
-prolyl & lysyl hydroxylases are inactive and tropocollagen cannot undergo the reactions that form covalent cross-links which results to scurv y
SCURVY - nutritional disorder characterized by bleeding gums, poor wound healing, an ultimately death.
is 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’
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 α 1-procollagen, procollagen N -peptidase, or lysyly hydroxylase.