Connective tissue genetic

The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the cycle. It also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the hver is the only tissue in which all occur to a significant extent. The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or replaced by connective tissue (as in cirrhosis). Very few, if any, genetic abnormalities of citric acid cycle enzymes have been reported such ab-normahties would be incompatible with life or normal development. 

Finally, we have to observe that all this chemistry of differentiation, of communication and of connective tissue formation has to be connected to changes in genetic content, that is ultimately of DNA. The DNA expresses all the novel proteins of synthesis, oxidation and hydrolysis involving the metals Fe, Cu, Zn, Mn... 

The many (possibly more than 30) types of collagens found in human connective tissues have substantially the same chemical structure consisting mainly of glycine with smaller amounts of proline and some lysine and alanine. In addition, there are two unusual amino acids, hydroxyproline and hydroxylysine, neither of which has a corresponding base-triplet or codon within the genetic code. There is therefore, extensive post-translational modification of the protein by hydroxylation and also by glycosylation reactions. 

Connective tissue is composed of apparently very different cells metabolically it is dynamic undergoing continual turnover and so to maintain health means that a balance must be achieved between biosynthesis and degradation. Cells in connective tissue are usually found embedded within a matrix composed of proteins with variable amounts of proteoglycan and genetically determined enzymatic defects in the production of the matrix may result in often serious pathologies. Metabolism in... 

W. A. Horton J. T. Hecht, Chondrodysplasias General Concepts and Diagnostic and Management Considerations. In Connective Tissue and Its Heritable Disorders Moiecuiar, Genetic, and Medical Aspects, P. M. Royce, B. Steinmann, Eds. Wiley-Liss New York, 2002 pp 901-908. 

L3. Liu, W. O., Oefner, P. J., et al. Denaturing HPLC-identified novel FBNl mutations, polymorphisms, and sequence variants in Marfan syndrome and related connective tissue disorders. Genet. Test. 1(4), I il-lAl (1997). 

Recall that collagen is an extracellular matrix protein that serves as a major constituent of many connective tissues (see figs. 4.10 to 4.13). Collagen fibrils have a distinctive banded pattern with a periodicity of 680 A. Individual fibrils are composed of three polypeptide chains wound around one another in a right-handed helix with a total length of 3,000 A. Each of the polypeptide chains in the triple helix has a repetitious tripeptide sequence, Gly-X-Y, where X is frequently a proline and Y is frequently a hy-droxyproline. The latter amino acid is not one of the 20 that are specified genetically, so it must be formed posttransla-tionally by a modification of some of the prolines. 

Byers PH, Cole WG Osteogenesis imperfecta, in Royce PM, Steinmann B (eds) Connective Tissue and Its Heritable Disorders. Molecular, Genetic, and Medical Aspects, 2nd edition. New York Wiley-Liss, 2002, pp. 385-430. 

Marfan syndrome is genetic disease that involves defects in the connective tissues of the body with the cardinal collection of abnormalities affecting the skeletal, ocular, and cardiovascular systems. It is inherited as an autosomal dominant disorder, meaning that inheriting only one defective gene from either the paternal or maternal side will lead to the disorder. Although the majority of mutations are inherited from one of the parents, approximately 25% of affected individuals develop Marfan syndrome as a result of a new mntation. The prevalence is 1/20,000 and the disorder is inherited with variable expression. This means that each individual may have a different combination of the possible clinical features that characterize the disorder. 

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