Procollagen peptides

Proline hydroxylase has been isolated and characterized and is known to contain a mononuclear nonheme ferrous iron center that is the catalytic active site of the enzyme, coordinated by two histidine and one aspartate side chains. The requirement for Fe(II) is reflected in the in vivo sensitivity of collagen formation to chelators specific for ferrous ion (e g. 2,2 -dipyridyl). In addition to the catalytic metal cofactor, the reaction requires a reducing cosubstrate, 2-oxoglutarate, dioxygen, and the procollagen peptide (equation 1). 

Lotterer, E., Gressner, AJM., Kropf, J., Grobe, E., Knebel, von, D., Bircher, J. Higher levels of serum aminoterminal type III procollagen peptide, and laminin in alcoholic than in nonalcoholic cirrhosis of equal severity. J. Hepatol. 1992 14 71—77... 

Muller, A., Krombholz, B., Pott, G., Machnik, G., Vollandt, R., Reinhardt, M., Jorke, D. Collagen peptidase and type III procollagen peptide serum levels in chronic liver diseases. Clin. Chim. Acta 1991 197 59-66... 

Bjermer, L., Lundgren, R. and Haellgren, R. (1989). Hyaluronan and type III procollagen peptide concentrations in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. Thorax 44, 126-131. 

Low, KB., Giancola, M.S., King, T.E.Jr. etal. (1992). Serum and bronchoalveolar lavage N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis. Am. Rev. Respir. Dis. 146, 701-706. 

Lung edema fluid IL-8, MMP-9, and procollagen peptide were higher in ARDS edema fluids than in hydrostatic edema. 

Pugin et al. (75) compared IL-8, matrix metalloproteinases (MMP-2 and MMP-9), and procollagen peptide III in the pulmonary edema fluid of patients with ARDS or hydrostatic edema. IL-8, MMP-9, and PCPIII were all elevated in the ARDS edema fluid as compared with the hydrostatic edema fluids. The outcomes of the patients were not reported. Interestingly, the clinical severity of illness scores were similar in the patients with ARDS and cardiogenic edema, so the edema fluid measurements were better than clinical criteria at identifying the patients with severe lung injury. 

Clark, J. G., Milberg, J. A., Steinberg, K. P., and Hudson, L. D. (1995) Type III procollagen peptide in the adult respiratory distress syndrome association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann. Intern. Med. 122,17-23. 

Many other peptides are synthesized as proproteins that require modifications before attaining biologic activity. Many of the posttranslational modifications involve the removal of amino terminal amino acid residues by specific aminopeptidases. Collagen, an abundant protein in the extracellular spaces of higher eukaryotes, is synthesized as procollagen. Three procol-... 

Before this "maturation" can occur there must be other modifications to procollagen. These begin while the peptide chains are still attached to ribosomes of the rough ER. Hydroxylases (Chapter 18) localized in the membranous vesicles of the ER convert some of the proline and lysine residues of the procollagen chains into 4-hydroxyproIine625 629 630 and hydroxylysine (Eqs. 8-6 and 8-7). Lesser amounts of 3-hydroxypro-line are formed. About 100 molecules of 4-hydrox-yproline and 50 of 5-hydroxylysine are created in each al chain. 

Within the extracellular space two procollagen peptidases act to cleave a 35-kDa peptide from the C terminus631 and a 20-kDa peptide from the N-terminal end of each of the three chains of the secreted procollagen. The amino acid composition of the peptides removed is quite unlike that of the remaining collagen monomer (also called tropocollagen) which contains one-third glycine and much proline. 

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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