Table 3.
Uremic retention solutes and their synthesizing enzymes’ mRNA abundance in HMP2. Presented uremic retention solutes had at least one enzyme’s mRNA represented in more than 90% of patients. The following information is given in parentheses for each enzyme: mRNA - percentage of patients who have mRNA for this enzyme; Q - quartile for this mRNA abundance; prot - percent of patients who have protein for this enzyme detected in proteome. The complete list is available in Supplementary Table S5.
| Uremic Retention Solutes | Number of Different Enzymes Where mRNA Detected | Percentage of Patients Who Have at Least One Enzyme’s mRNA for This Uremic Retention Solute | Enzymes |
|---|---|---|---|
| Argininic Acid | 11 | 99.73% | Nitric-oxide synthase (NADPH) (mRNA: 2.59%, Q1, prot: NA); Glycine amidinotransferase (mRNA: 0.68%, Q1, prot: NA); Arginine N-succinyltransferase (mRNA: 5.17%, Q1, prot: NA); Arginine--pyruvate transaminase (mRNA: 0.14%, Q1, prot: NA); Arginine kinase (mRNA: 9.12%, Q2, prot: NA); [Protein ADP-ribosylarginine] hydrolase (mRNA: 2.86%, Q2, prot: NA); Arginase (mRNA: 82.31%, Q2, prot: 0.22%); Arginine deiminase (mRNA: 83.27%, Q2, prot: 8.22%); Arginine decarboxylase (mRNA: 91.29%, Q2, prot: 32%); Argininosuccinate lyase (mRNA: 99.18%, Q4, prot: 14%); Arginine--tRNA ligase (mRNA: 99.59%, Q4, prot: 42%) |
| S-Adenosylhomocysteine | 64 | 99.59% | Homocysteine S-methyltransferase (mRNA: 4.49%, Q1, prot: NA); Protein-S-isoprenylcysteine O-methyltransferase (mRNA: 0%, QNA, prot: NA); Caffeoyl-CoA O-methyltransferase (mRNA: 8.98%, Q1, prot: NA); Uroporphyrinogen-III C-methyltransferase (mRNA: 52.65%, Q1, prot: 1.33%); Site-specific DNA-methyltransferase (cytosine-N(4)-specific) (mRNA: 2.45%, Q1, prot: NA); Precorrin-2 C(20)-methyltransferase (mRNA: 57.96%, Q1, prot: NA); Precorrin-3B C(17)-methyltransferase (mRNA: 78.91%, Q2, prot: NA); Precorrin-6B C(5,15)-methyltransferase (decarboxylating) (mRNA: 86.94%, Q2, prot: 0.22%); Precorrin-4 C(11)-methyltransferase (mRNA: 71.56%, Q1, prot: NA); Trans-aconitate 2-methyltransferase (mRNA: 8.98%, Q1, prot: 0.22%)... (see all 64 enzymes in ST 4) |
| Orotidine | 2 | 99.59% | Orotate phosphoribosyltransferase (mRNA: 99.05%, Q4, prot: 35.78%); Orotidine-5’-phosphate decarboxylase (mRNA: 99.32%, Q4, prot: 63.78%) |
| Uridine | 7 | 99.46% | Pyrimidine-nucleoside phosphorylase (mRNA: 50.88%, Q1, prot: 0.22%); Uridine phosphorylase (mRNA: 91.84%, Q2, prot: 4.67%); Uridine kinase (mRNA: 99.05%, Q4, prot: 2.89%); 5’-nucleotidase (mRNA: 98.64%, Q4, prot: 1.56%); 3’-nucleotidase (mRNA: 19.46%, Q1, prot: 0.89%); Uridine nucleosidase (mRNA: 0.54%, Q1, prot: NA); Cytidine deaminase (mRNA: 87.62%, Q2, prot: 11.56%) |
| Hypoxanthine | 8 | 99.32% | Xanthine dehydrogenase (mRNA: 80%, Q2, prot: 0.89%); Purine-nucleoside phosphorylase (mRNA: 99.18%, Q4, prot: 62.67%); Thymidine phosphorylase (mRNA: 58.5%, Q1, prot: 0.89%); S-methyl-5’-thioinosine phosphorylase (mRNA: 0.41%, Q1, prot: NA); Hypoxanthine phosphoribosyltransferase (mRNA: 97.69%, Q3, prot: 6.89%); Purine nucleosidase (mRNA: 28.44%, Q1, prot: NA); Ribosylpyrimidine nucleosidase (mRNA: 3.67%, Q1, prot: NA); Adenine deaminase (mRNA: 96.46%, Q2, prot: 0.22%) |
| Cytidine | 6 | 99.32% | Pyrimidine-nucleoside phosphorylase (mRNA: 50.88%, Q1, prot: 0.22%); Uridine kinase (mRNA: 99.05%, Q4, prot: 2.89%); 5’-nucleotidase (mRNA: 98.64%, Q4, prot: 1.56%); 3’-nucleotidase (mRNA: 19.46%, Q1, prot: 0.89%); Ribosylpyrimidine nucleosidase (mRNA: 3.67%, Q1, prot: NA); Cytidine deaminase (mRNA: 87.62%, Q2, prot: 11.56%) |
| Orotic Acid | 4 | 99.32% | Dihydroorotate dehydrogenase (NAD(+)) (mRNA: 91.43%, Q3, prot: 14.44%); Dihydroorotate dehydrogenase (quinone) (mRNA: 93.47%, Q3, prot: 0.44%); Dihydroorotate oxidase (fumarate) (mRNA: 2.86%, Q1, prot: NA); Orotate phosphoribosyltransferase (mRNA: 99.05%, Q4, prot: 35.78%) |
| Nicotinamide | 7 | 99.18% | Purine-nucleoside phosphorylase (mRNA: 99.18%, Q4, prot: 62.67%); Nicotinamide phosphoribosyltransferase (mRNA: 0.41%, Q1, prot: NA); NAD(+) ADP-ribosyltransferase (mRNA: 0.41%, Q2, prot: 0%); Purine nucleosidase (mRNA: 28.44%, Q1, prot: NA); Uridine nucleosidase (mRNA: 0.54%, Q1, prot: NA); ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (mRNA: 0%, QNA, prot: NA); Nicotinamidase (mRNA: 19.32%, Q1, prot: NA) |
| Xanthine | 6 | 99.18% | Xanthine dehydrogenase (mRNA: 80%, Q2, prot: 0.89%); Purine-nucleoside phosphorylase (mRNA: 99.18%, Q4, prot: 62.67%); Xanthine phosphoribosyltransferase (mRNA: 98.37%, Q4, prot: 16.22%); Hypoxanthine phosphoribosyltransferase (mRNA: 97.69%, Q3, prot: 6.89%); Purine nucleosidase (mRNA: 28.44%, Q1, prot: NA); Guanine deaminase (mRNA: 42.04%, Q1, prot: 0%) |
| Inosine | 6 | 99.18% | Purine-nucleoside phosphorylase (mRNA: 99.18%, Q4, prot: 62.67%); Inosine kinase (mRNA: 17.69%, Q1, prot: NA); 5’-nucleotidase (mRNA: 98.64%, Q4, prot: 1.56%); Purine nucleosidase (mRNA: 28.44%, Q1, prot: NA); Ribosylpyrimidine nucleosidase (mRNA: 3.67%, Q1, prot: NA); Adenosine deaminase (mRNA: 36.46%, Q1, prot: 0.22%) |
| Myoinositol | 5 | 99.18% | Inositol 2-dehydrogenase (mRNA: 16.33%, Q1, prot: 0.89%); Galactinol--raffinose galactosyltransferase (mRNA: 0.27%, Q2, prot: NA); CDP-diacylglycerol--inositol 3-phosphatidyltransferase (mRNA: 3.54%, Q2, prot: NA); Inositol-phosphate phosphatase (mRNA: 87.48%, Q2, prot: 0.22%); Alpha-galactosidase (mRNA: 99.05%, Q3, prot: 11.56%) |
| Xanthosine | 3 | 99.18% | Purine-nucleoside phosphorylase (mRNA: 99.18%, Q4, prot: 62.67%); 5’-nucleotidase (mRNA: 98.64%, Q4, prot: 1.56%); Purine nucleosidase (mRNA: 28.44%, Q1, prot: NA) |
| Methylglyoxal | 8 | 99.05% | Aldehyde reductase (mRNA: 11.43%, Q1, prot: NA); Methylglyoxal reductase (NADPH) (mRNA: 5.71%, Q2, prot: NA); Glycerol dehydrogenase (mRNA: 54.01%, Q1, prot: 7.11%); Glyoxylate reductase (NADP(+)) (mRNA: 17.28%, Q1, prot: NA); Lactaldehyde dehydrogenase (mRNA: 24.76%, Q1, prot: 0.89%); D-lactate dehydratase (mRNA: 15.78%, Q1, prot: 0.22%); Methylglyoxal synthase (mRNA: 98.91%, Q4, prot: 58.22%); Lactoylglutathione lyase (mRNA: 66.8%, Q2, prot: 0.67%) |
| Homocysteine | 8 | 99.05% | Homocysteine S-methyltransferase (mRNA: 4.49%, Q1, prot: NA); Methionine synthase (mRNA: 82.45%, Q2, prot: 0.44%); 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase (mRNA: 38.23%, Q1, prot: 18.67%); Cystathionine gamma-synthase (mRNA: 29.52%, Q1, prot: 0.67%); O-acetylhomoserine aminocarboxypropyltransferase (mRNA: 94.01%, Q2, prot: 21.56%); Adenosylhomocysteinase (mRNA: 97.82%, Q3, prot: 16.22%); Cystathionine beta-synthase (mRNA: 4.35%, Q1, prot: NA); S-ribosylhomocysteine lyase (mRNA: 97.82%, Q3, prot: 42.89%) |
| Sorbitol | 4 | 99.05% | L-iditol 2-dehydrogenase (mRNA: 63.27%, Q1, prot: 4.89%); Aldehyde reductase (mRNA: 11.43%, Q1, prot: NA); Hexokinase (mRNA: 33.88%, Q1, prot: NA); Alpha-galactosidase (mRNA: 99.05%, Q3, prot: 11.56%) |
| Phenylacetic acid | 6 | 98.37% | Phenylacetaldehyde dehydrogenase (mRNA: 4.08%, Q1, prot: NA); Aldehyde dehydrogenase (NAD(P)(+)) (mRNA: 5.85%, Q1, prot: NA); Penicillin amidase (mRNA: 62.99%, Q1, prot: 0.44%); Amidase (mRNA: 1.09%, Q1, prot: NA); Nitrilase (mRNA: 0.27%, Q1, prot: NA); Phenylacetate--CoA ligase (mRNA: 98.23%, Q4, prot: 12.44%) |
| Putrescine | 11 | 98.1% | Non-specific polyamine oxidase (mRNA: 0.41%, Q2, prot: NA); Putrescine carbamoyltransferase (mRNA: 1.5%, Q1, prot: NA); Diamine N-acetyltransferase (mRNA: 83.4%, Q2, prot: NA); Spermidine synthase (mRNA: 76.87%, Q2, prot: 0.44%); Homospermidine synthase (mRNA: 0.54%, Q1, prot: NA); Diamine transaminase (mRNA: 0.14%, Q1, prot: NA); Putrescine aminotransferase (mRNA: 16.19%, Q1, prot: NA); N-carbamoylputrescine amidase (mRNA: 28.84%, Q1, prot: NA); Agmatinase (mRNA: 74.29%, Q2, prot: 1.33%); Ornithine decarboxylase (mRNA: 48.71%, Q2, prot: 2.89%); Glutamate--putrescine ligase (mRNA: 6.8%, Q1, prot: NA) |
| Quinolinic Acid | 2 | 98.1% | Nicotinate-nucleotide diphosphorylase (carboxylating) (mRNA: 77.55%, Q2, prot: 8.89%); Quinolinate synthase (mRNA: 97.82%, Q3, prot: 4.67%) |
| 3-hydroxyanthranilic acid | 4 | 97.82% | Catalase peroxidase (mRNA: 4.9%, Q2, prot: 5.11%); Catalase (mRNA: 97.69%, Q3, prot: 22.22%); 3-hydroxyanthranilate 3,4-dioxygenase (mRNA: 0.27%, Q2, prot: NA); Kynureninase (mRNA: 0.27%, Q2, prot: NA) |
| Urea | 8 | 96.87% | Urease (mRNA: 58.78%, Q2, prot: 0.67%); Arginase (mRNA: 82.31%, Q2, prot: 0.22%); Agmatinase (mRNA: 74.29%, Q2, prot: 1.33%); Creatinase (mRNA: 0.95%, Q2, prot: NA); Allantoicase (mRNA: 0.68%, Q2, prot: NA); Guanidinobutyrase (mRNA: 0.27%, Q1, prot: NA); Ureidoglycolate lyase (mRNA: 5.44%, Q1, prot: 0.22%); Urea carboxylase (mRNA: 27.76%, Q1, prot: NA) |
| Anthranilic acid | 5 | 96.33% | Anthranilate phosphoribosyltransferase (mRNA: 94.29%, Q2, prot: 2%); Arylformamidase (mRNA: 0.41%, Q1, prot: NA); Kynureninase (mRNA: 0.27%, Q2, prot: NA); Anthranilate synthase (mRNA: 55.1%, Q1, prot: 0.89%); Anthranilate--CoA ligase (mRNA: 0.27%, Q1, prot: NA) |
| Phenol | 3 | 89.66% | Arylesterase (mRNA: 16.73%, Q1, prot: NA); 4-hydroxybenzoate decarboxylase (mRNA: 3.95%, Q2, prot: NA); Tyrosine phenol-lyase (mRNA: 86.67%, Q3, prot: NA) |
| Uric Acid | 3 | 80.00% | FAD-dependent urate hydroxylase (mRNA: 0.68%, Q1, prot: NA); Xanthine dehydrogenase (mRNA: 80%, Q2, prot: 0.89%); 8-oxoguanine deaminase (mRNA: 0%, QNA, prot: NA) |
| Trimethylamine | 3 | 78.23% | Betaine reductase (mRNA: 75.65%, Q3, prot: 0.44%); Trimethylamine dehydrogenase (mRNA: 0.27%, Q1, prot: NA); Trimethylamine-N-oxide reductase (cytochrome c) (mRNA: 10.2%, Q1, prot: 0.44%) |
| Hippuric acid | 1 | 44.63% | Hippurate hydrolase (mRNA: 44.63%, Q1, prot: NA) |
| Monomethylamine | 1 | 42.99% | Sarcosine reductase (mRNA: 42.99%, Q1, prot: 0.44%) |
| Creatine | 3 | 28.44% | Creatine kinase (mRNA: 1.5%, Q1, prot: 0%); Creatininase (mRNA: 26.39%, Q1, prot: 0.67%); Creatinase (mRNA: 0.95%, Q2, prot: NA) |
| Creatinine | 1 | 26.39% | Creatininase (mRNA: 26.39%, Q1, prot: 0.67%) |
| Oxalate | 3 | 22.72% | Formyl-CoA transferase (mRNA: 20.54%, Q1, prot: 1.33%); CoA:oxalate CoA-transferase (mRNA: 3.27%, Q1, prot: 0.22%); Oxalate--CoA ligase (mRNA: 0.14%, Q1, prot: NA) |
| Mannitol | 3 | 21.9% | D-arabinitol 4-dehydrogenase (mRNA: 0.68%, Q1, prot: NA); Mannitol dehydrogenase (mRNA: 0.41%, Q1, prot: NA); Mannitol 2-dehydrogenase (mRNA: 21.22%, Q1, prot: NA) |
| Phenol sulfate | 2 | 20.27% | Aryl-sulfate sulfotransferase (mRNA: 5.99%, Q1, prot: NA); Arylsulfatase (mRNA: 15.37%, Q1, prot: NA) |
| Arab(in)itol | 1 | 11.43% | Aldehyde reductase (mRNA: 11.43%, Q1, prot: NA) |
| Trimethylamine-N-oxide | 1 | 10.2% | Trimethylamine-N-oxide reductase (cytochrome c) (mRNA: 10.2%, Q1, prot: 0.44%) |
| Pseudouridine | 1 | 9.66% | Pseudouridine kinase (mRNA: 9.66%, Q1, prot: NA) |
| p-Cresyl sulfate | 2 | 9.12% | 4-hydroxyphenylacetate decarboxylase (mRNA: 0.95%, Q2, prot: NA); 2-iminoacetate synthase (mRNA: 8.71%, Q1, prot: NA) |
| 3-(3-Hydroxyphenyl) propanoic acid | 1 | 9.12% | 3-(3-hydroxy-phenyl)propanoic acid hydroxylase (mRNA: 9.12%, Q1, prot: NA) |
| a-keto-d-Guanidinovaleric Acid | 2 | 5.85% | D-amino-acid transaminase (mRNA: 5.71%, Q1, prot: NA); Arginine--pyruvate transaminase (mRNA: 0.14%, Q1, prot: NA) |
| Indole-3-acetic acid | 3 | 3.95% | Aldehyde dehydrogenase (NAD(+)) (mRNA: 2.72%, Q1, prot: NA); Amidase (mRNA: 1.09%, Q1, prot: NA); Nitrilase (mRNA: 0.27%, Q1, prot: NA) |
| y-guanidinobutyric Acid | 3 | 1.9% | Glycine amidinotransferase (mRNA: 0.68%, Q1, prot: NA); Amidase (mRNA: 1.09%, Q1, prot: NA); Guanidinobutyrase (mRNA: 0.27%, Q1, prot: NA) |
| Hyaluronic acid (Hyaluronan) | 1 | 1.9% | Hyaluronan synthase (mRNA: 1.9%, Q1, prot: 0.22%) |
| Gentisic acid | 1 | 1.22% | 3-hydroxybenzoate 6-monooxygenase (mRNA: 1.22%, Q1, prot: 0.22%) |
| Kinurenine | 4 | 0.95% | Kynurenine 3-monooxygenase (mRNA: 0%, QNA, prot: NA); Kynurenine--oxoglutarate transaminase (mRNA: 0.82%, Q2, prot: 0%); Arylformamidase (mRNA: 0.41%, Q1, prot: NA); Kynureninase (mRNA: 0.27%, Q2, prot: NA) |
| Dimethylamine | 2 | 0.95% | Trimethylamine dehydrogenase (mRNA: 0.27%, Q1, prot: NA); Dimethylargininase (mRNA: 0.68%, Q2, prot: NA) |
| Kynurenic Acid | 1 | 0.82% | Kynurenine--oxoglutarate transaminase (mRNA: 0.82%, Q2, prot: 0%) |
| Taurocyamine | 1 | 0.68% | Glycine amidinotransferase (mRNA: 0.68%, Q1, prot: NA) |
| Asymmetric Dimethylarginine (ADMA) | 1 | 0.68% | Dimethylargininase (mRNA: 0.68%, Q2, prot: NA) |