Collagen propeptides

Type I collagen is synthesized as a precursor, procoUagen, containing both N- and C-terminal extensions. These extensions, or propeptides, are cleaved from type I procoUa-gen during coUagen formation. Collagen propeptides are a marker of bone formation. Several immunoassays have been developed to measure the N-terminal (PINP) and C-terminal (pjCp)3 - o>527 propeptides. 

Because type 1 collagen is also the major matrix of several other tissues, collagen propeptides are not as sensitive or specific for bone formation as osteocalcin or BAP. Measurement of procoUagen peptides may be helpful for assessing bone formation in patients treated with 1,25-dihydroxyvitamin D or in patients with abnormal concentrations of this hormone when osteocalcin and BAP may be misleading. 

Matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TMP), and collagen propeptides (PIIINP) are also indicative of remodeling that occurs during cardiac hypertrophy, but are also nonspecific and consistent with more advanced hypertrophy than occurs in short-duration animal studies. A panel consisting of MMP-7, MMP-9, TIMP-1, PIIINP, and NTproBNP has shown promise in predicting the presence of cardiac hypertrophy in humans with hypertension and may prove useful in animal studies however, further research is needed (Zile et al., 2011). Osteoprotegerin (OPG), a member of the TNF receptor superfamily, has shown promise as a biomarker of cardiac hypertrophy however, little is known regarding the utihty of OPG in the context of nonclinical safety studies (Coutinho et al., 2011 Koyama et al., 2014). 

Collagen chains are synthesized as longer precursors, called procollagens, with globular extensions—propeptides of about 200 residues—at both ends. These procollagen polypeptide chains are transported into the lumen of the rough endoplasmic reticulum where they undergo hydroxylation and other chemical modifications before they are assembled into triple chain molecules. The terminal propeptides are essential for proper formation of triple... 

Type I collagen molecules are heterotrimeric molecules with an a chain composition of two al (I) chains and one o 2(I) chain from the COLlAl and COLl A2 genes, respectively. This a chain composition is written as [a 1(1)] 20 2 (I). A type I collagen molecule is synthesized as a procollagen type I molecule. The N- and C-terminal propeptides are cleaved as part of the processing in tissues and are called N- and C-propeptides, respectively. The human pro-o (I) and pro-o 2(I) have 246 and 247 residues in their C-propeptides, respectively. The C-propeptide contains interchain disulfide bonds, which are important for the stabilization of the three a chains in the endoplasmic reticulum (ER). 

Processing of a newly synthesized type V procollagen molecule is also different from that of type I collagen. BMP-1, which is the C-propeptidase of type I, II, and III collagens, cleaves the N-terminal propeptide of the pro-al(V) chain, and a furin-like proteinase cleaves the C-terminal propeptide. The tyrosine residue in the N-terminal NC domain of type V collagen is sulfated. This modification might be related to... 

Removal of the N- and C-terminal propeptides from fully folded procollagens occurs only after transport of procollagens across the Golgi stacks and results in collagen molecules that are then able to assemble into fibrils. C-proteinase activity is possessed by members of the tolloid family of zinc metalloproteinases,... 

All of the 12 fibril-forming a chains share a long uninterrupted collagenous domain flanked by N- and C-terminal NC propeptides. The a chains assemble into at least 12 type-specific protomers, characterized as homo- and heterotrimers. The chains of fibrillar collagens associate first through a series of noncovalent interactions between the C-terminal NC domains (NCI), which provide correct alignment and registration for... 

The propeptides are cleaved from the ends of procollagen by proteases to form collagen molecules (also called tropocoUagen). 

This enzyme [EC 3.4.24.14], also known as procollagen A-proteinase, catalyzes the hydrolysis of the A-propep-tide of the collagen chain a-l(l) at Pro—Gin and of a-2(11) chain at Ala—Gin. As a result, A-terminal propeptides of type I and II collagens are released prior to fibril assembly. However, it does not act on type III procollagen. 

Extracellular cleavage of procollagen molecules After their release, the procollagen molecules are cleaved by N- and C-pro-collagen peptidases, which remove the terminal propeptides, releasing triple-helical collagen molecules. 

Blood Alkaline phosphatase (bone-specific) Osteocalcin Procollagen type I carboxy-terminal propeptide (PICP) Procollagen type I amino-terminal propeptide (PINP) Procollagen type III amino-terminal propeptide (PIIINP) Blood Acid phosphatase (acid-resistant) Type I collagen carboxy-terminal telopeptide (ICTP) Urine Calcium Hydroxyproline Cross-linked peptides (pyridinium and deoxypyridinoline)... 

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