Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome

Table 3

The table shows the following: (I) the main metabolic classification (referred to as Super Pathway in the Supplementary Table in Supplementary Material available online at http://dx.doi.org/10.1155/2015/943430) together with the number of significantly altered metabolites belonging to this class relative to the total number of examined metabolites from this class; (II) the subclass(es) (subpathway, see also Figure 3) within the corresponding main class showing an enrichment value >5 followed by the number of significantly altered single metabolites relative to the total number of investigated metabolites for this subclass; and (III) the single metabolites showing significant differences, whether they were increased (↑) or decreased (↓) for patients with capillary leak syndrome, and a brief summary of known and relevant functional effects on endothelial cells, renal function, or vascular biology. The main class/subclasses are ranked according to the score presented in Figure 3 (value given in parenthesis after the subclass identification). The nucleotide main class (super pathway) included three different subclasses/subpathways that showed an enrichment value >5; 6 of the 36 metabolites in the nucleotide class differed significantly between the two patient subsets (2 in each subclass, indicated as 6/36). The corresponding numbers for the Main Class Amino acids were 7/171, 2, and 5, respectively, for 2 different subclasses.

(I) Main metabolic classification (super pathway)	(II) Subclass (subpathway)	(III) Metabolite (biochemical name)
Nucleotide 6/36	Pyrimidine metabolism, cytidine containing 2/2 (25.53)	↑cytidine, ↑N4-acetylcytidine; Animal models suggest that cytidine can function as a cardiovascular regulator through binding to adenosine A1 and A2 receptor [33].
Carbohydrate 2/24	Aminosugar metabolism 2/3 (17.02)	↑glucuronate; Glucuronate is important for the synthesis of several glycoproteins (see Table 4).; ↑erythronate; Erythronic acid is important in mitochondrial metabolism, and it is normally present only at low levels [34].
Nucleotide 6/36	Purine metabolism, guanine containing 2/6 (17.02)	↑7-methylguanine, ↑N2,N2-dimethylguanosine; There is a metabolic interaction between adenosine and guanosine metabolism; extracellular ADT and ATP are known angioregulatory mediators [35].
Lipid 1/303	Eicosanoid 1/6 (8.51)	↑Thromboxane B2; Thromboxane B2 is the main degradation product of Thromboxane A2 [36] that can be released by endothelial cells and bind to specific receptors expressed both by endothelium and smooth muscle vascular cells [36–38]. Receptor activation usually promotes vasoconstriction [36].
Amino acids 2/172 (7.86)	Urea cycle; Arginine and Proline Metabolism 2/13	↑homocitrulline; ↑N-delta-acetylornithine; Both metabolites are important for the urea cycle; ornithine enters mitochondria and reacts with carbamoyl phosphate to form citrulline that enters the urea cycle.
Nucleotide 6/36	Purine metabolism, adenine containing 2/7 (7.30)	↑adenosine, ↑N6-carbamoylthreonyladenosine; Adenosine is a well-characterized cardiovascular regulator and binds to specific receptors [39, 40]. A2A and A2B receptors are also expressed by endothelial cells [66].
Amino acids 5/172	Methionine, cysteine, SAM, and taurine metabolism 5/16 (6.38)	↑N-acetylmethionine; ↑N-formylmethionine; ↑Methionine sulfone; N-acetylmethionine can be formed by normal cells from methionine, but it is also a bioavailable form of methionine in humans [41]. Methionine sulfone may reflect the nutritional status.; ↓hypotaurine; ↓taurine; As reviewed recently taurine is a β-amino acid that is not incorporated into proteins and can serve as an intracellular osmolyte [42]. It is one of the major osmolytes (together with betaine) in the renal medulla. A renal adaptive response to dietary intake seems to conserve the total taurine body pool through the balance between reabsorption and excretion. Taurine seems to be a regulator of renal blood flow and influences the flow within all types of vessels, and it also seems to stabilize the endothelium.