HYPERHOMOCYSTEINEMIA AS A RESPONSE TO STRESS

N and S maintain tightly correlated ratios in tissues of both healthy subjects8 and diseased patients.167 Acute stressful conditions of any cause unleash a shower of many cytokines that fulfill a myriad of autocrine, para- crine, and endocrine functions.168 As a consequence, enhanced tissue proteolysis throughout the body ensues, allowing the redirection of AA residues toward the pref- erential overproduction of acute-phase reactants and repair proteins by the liver and at the site of injury.169 The rate of protein degradation usually exceeds that of protein undergoing neosynthesis,170,171 leading to a negative N balance with subsequent depletion of TBN reserves. The increased urinary excretion of N catabolites (mainly urea, but also creatinine, NH4+, 3-CH3-histidine, and other minor compounds) demonstrates that both metabolic and structural tissues participate in the adap- tive responses to injury in proportion to the magnitude of initial impact.31,170,171 In very aggressive conditions (burns) affecting adult men, urinary output of N may be as high as 250 g of N per week, which corresponds to a loss of 6–7 kg of LBM31 or 12–14% of metabolically active tissues.30 Major stressful disorders are associated with massive urinary excretion of S,167,172 which depletes endogenous pools of TBS. In stressors of medium severity (bone fracture), S spillover has been estimated to be 17 g of S per week, or more than 10% of TBS body stores. Interestingly enough, measurement of S and N urinary losses yields values very close to the 1:14 ratio that char- acterizes mammalian tissues,8,167 indicating that TBN and TBS pools exhibit concomitant degradation patterns throughout the course of injury.