Serum galactosylhydroxylysyl glucosyltransferase in acute myocardial infarction and during subsequent collagen scar formation

Changes in serum galactosylhydroxylysyl glucosyltransferase, an enzyme catalysing one of the intracellular post-translational modifications in collagen biosynthesis, were studied in twenty-four patients with acute myocardial infarction. The enzyme activity was monitored for 18 days from the onset of infarction, and at least a two-peaked pattern was observed. The first peak corresponded to the stage of acute myocardial injury, there being a highly significant correlation between the maximal values for serum glucosyltransferase and alpha-hydroxybutyrate dehydrogenase. An average decreasing in serum glucosyltransferase activity of 41%, was noted during the following 24 h. A new gradual rise in serum glucosyltransferase activity, interpreted as indicating myocardial collagen scar formation, was observed 5 days after the onset of infarction, when the serum enzyme activities indicating myocardial injury had already declined. The average daily values for serum glucosyltransferase between 6 and 18 days correlated highly significantly with the maximal value for serum alpha-hydroxybutyrate dehydrogenase, which serves as a relative estimate of the size of the original myocardial infarction area. The data further suggest that certain other factors including heart failure and/or various drug treatments may also affect the magnitude of this second peak.     

Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease

Abstract. Serum immunoreactive prolyl hydroxylase protein was measured in sixty-five patients with liver disease, and liver prolyl hydroxylase activity, immunoreactive prolyl hydroxylase protein and collagen hydroxyproline in forty of these patients. Serum immunoreactive prolyl hydroxylase protein was above the 95% confidence limit of the controls in most patients with primary biliary cirrhosis, portal cirrhosis, acute hepatitis and cancer with liver metastases, but below this in most patients with fatty liver, chronic active hepatitis, extrahepatic cholestasis, cholangitis, cancer without liver metastases and other malignant diseases. Elevated serum immunoreactive prolyl hydroxylase protein decreased rapidly with time in acute hepatitis but not in primary biliary cirrhosis. Liver prolyl hydroxylase activity and immunoreactive prolyl hydroxylase protein were elevated in the same diseases as serum immunoreactive prolyl hydroxylase protein, and correlated significantly with the latter whereas no correlation was found between serum immunoreactive prolyl hydroxylase protein and collagen hydroxyproline. Serum immunoreactive prolyl hydroxylase protein correlated highly significantly with serum alkaline phosphatase and weakly with serum aspartate aminotransferase in primary biliary cirrhosis, but not in any other disease. No correlation was found between serum immunoreactive prolyl hydroxylase protein and other tests of liver function. The results suggest that changes in serum immunoreactive prolyl hydroxylase protein in liver disease primarily reflect changes in this enzyme in the hepatic tissue, and that assays of serum immunoreactive prolyl hydroxylase in liver disease may give useful information on the actual hepatic collagen synthesis.     

Three serum markers of collagen biosynthesis in Nigerians with cirrhosis and various infectious diseases

Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity, and the aminoterminal propeptide of type III procollagen (S-Pro(III)-N-P) were measured in twenty patients with cirrhosis and ninety with various infectious diseases, and the values were compared with those in sixty apparently healthy Nigerians. The means for all three markers were elevated significantly in the patients with cirrhosis (P less than 0.001), acute viral hepatitis (P less than 0.001), amoebic liver abscess (P less than 0.001) and the early stages of Schistosoma mansoni infection (P less than 0.001 for S-Pro(III)-N-P, P less than 0.005 for the two other markers). The mean S-Pro(III)-N-P was also distinctly elevated during the early stages of Schistosoma haematobium infection (P less than 0.01) and filariasis (P less than 0.001), whereas none of the three markers was elevated during an acute attack of malaria. Significant correlations were found between the values for the three markers within the groups of patients with cirrhosis, amoebic liver abscess and schistosomiasis, the correlations for the pooled group of all patients being highly significant (P less than 0.001). The data suggest that elevated hepatic collagen formation is found not only in cirrhosis but also in several infectious diseases. The three serum markers may be useful for showing the stages of active collagen formation in various liver diseases and for predicting the development of fibrosis in acute cases if the values remain elevated.     

Basement membrane components and galactosylhydroxylysyl glucosyltransferase in suction blisters of human skin

Basement membrane components and collagen biosynthesis were studied in suction blisters in human skin. The basement membrane components were characterized by immunofluorescence using specific antibodies to type IV collagen, laminin and fibronectin, and collagen biosynthesis was studied by assaying galactosylhydroxylysyl glucosylatransferase. In suction blisters, the separation of epidermis and dermis occurred above the lamina lucida, indicating that the basement membrane, composed of lamina lucida and lamina densa, forms a mechanically strong entity. During the regeneration phase of blisters, type Iv collagen and laminin were not observed in the old epidermal blister roof. This indicates that keratinocytes when separated from the underlying basement membrane or connective tissue do not synthesize laminin or type IV collagen. Galactosylhydroxylysyl glucosyltransferase activity could be demonstrated in blister fluid and was about the same as in serum when expressed on the basis of protein in fresh blisters. It increased by 2-3 fold during the repair of blisters, indicating that there was local production of this enzyme. Further studies revealed that pure epidermis contained galactosylyhdroxylysyl glucosyltransferase and hydroxyprolineand this suggests that epidermis may synthesize some collagen type which, according to these studies, is not type IV (basement memebrane) collagen.