Connective tissue, homocysteine

Accumulation of homocysteine and reduced transsulfation of various compounds leads to abnormalities in connective tissue structures that cause altered blood vessel wall structure, loss of skeletal bone density (osteoporosis), dislocated optic lens (ectopia lentis), and increased risk of blood clots. 

Vascular fragility may also result from reduced sulfation of proteoglycans in connective tissue, as may also occur in hyperhomocysteinemia (Section 10.3.4.2). Dehydroascorbate catalyzes the oxidation of homocysteine to ho-mocysteic acid, which is the precursor of PAPS, the sulfate donor for sulfation reactions (McCuUy, 1971). 

Several inherited disorders of methionine metabolism (Chapter 17) give rise to exeessive production of homocysteine, HS-CH2-CH2CH(NH3 )COO , and its excretion in urine. The most common form of homocystinuria is due to a deficiency of cystathionine synthase (Chapter 17). A major clinical manifestation of homocystinuria is connective tissue abnormalities that are probably due to the accumulation of homocysteine, which either inactivates the reactive aldehyde groups or impedes the formation of polyfunctional cross-links. 

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