title: Methionine Metabolites in Patients With Sepsis.
abstract: OBJECTIVE
  Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality.
  
  
  METHODS
  This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors.
  
  
  RESULTS
  Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction.
  
  
  CONCLUSIONS
  Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Orren
authors: O
authors: Wexler
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Michael S
authors: MS
authors: Gough
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Mary Anne M
authors: MAM
authors: Morgan
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Cynthia M
authors: CM
authors: Mack
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Michael J
authors: MJ
authors: Apostolakos
authors: 2 Department of Nursing, University of Rochester Medical Center, Rochester, NY, USA.
authors: Kathleen P
authors: KP
authors: Doolin
authors: 3 Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Robert A
authors: RA
authors: Mooney
authors: 4 Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
authors: Erland
authors: E
authors: Arning
authors: 4 Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
authors: Teodoro
authors: T
authors: Bottiglieri
authors: 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors: Anthony P
authors: AP
authors: Pietropaoli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D055499:Catheter-Related Infections / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D017052:Hospital Mortality; D006801:Humans; D059413:Intraabdominal Infections / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality; D012874:Skin Diseases, Infectious / Q000378:metabolism; D014552:Urinary Tract Infections / Q000378:metabolism
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine
keywords: S-adenosylhomocysteine; S-adenosylmethionine; homocysteine; sepsis