Supplementary Table 1: Glucose metabolism in patients with psoriasis Metabolites Changes Pathways Implication References In Peripheral blood α-Ketoglutarate acts as a cycle intermediate and is α-ketoglutaric acid higher Tricarboxylic acid cycle converted to , which downstream produces 26 for collagen synthesis The glycolytic activity of psoriasis patients is greatly enhanced Glycolysis and pyruvate Lactic acid higher and can provide a favorable microenvironment for 27 metabolism keratinogenic cell proliferation Mitochondria oxidized Aspartic acid higher 26,27 respiratory chain The increase in glutamate may be secondary to increased Mitochondria oxidized Glutamic acid higher glutamine requirements during conditions of rapid protein 24,26 respiratory chain synthesis and cytokine production higher Valine, and Excess BCAA may worsen insulin resistance, which leads to 28,69,70,71, higher isoleucine biosynthesis the accumulation of inflammatory cytokines 28,69,70,71, Succinate lower Tricarboxylic acid cycle 83 In Lesion Anaerobic oxidation of glucose; Myoinositol lower Synthesis of 21,24 phosphatidylinositol by gluconeogenesis Glucose lower Glycometabolism 21 The reduction of lactic acid in local lesions is most likely due to Glycolysis and pyruvate Lactic acid lower metabolic changes in sweat glands and keratinocytes or 24 metabolism obstruction of sweat ducts. In Urine Citrate lower Tricarboxylic acid cycle 25 lower Alanine glucose cycle 25 Methylsuccinate lower Tricarboxylic acid cycle 25 Lactose higher 137 6-phosphate Anaerobic fermentation Oxoglutaric acid lower 137 of glucose Glucosamine lower 137 6-sulfate Oxidation to succinic γ-Hydroxybutyric acid and then involved in lower 137 acid the tricarboxylic acid cycle BCAAs: Branched-chain amino acids.

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Supplementary Table 2: Lipid metabolism in patients with psoriasis Metabolites Changes Pathways Implication References In Peripheral blood Crotonic acid lower Fatty acid biosynthesis 27 Ethanolamine lower Phospholipid biosynthesis 27 2-hydroxysebacic acid lower Fatty acid metabolism 27 Azelaic acid lower Fatty acid metabolism 27 13-octadecenoic acid lower Fatty acid metabolism 27 Urea higher 27 Lipid metabolism and bile acid Cholesterol higher 83 synthesis Produce inflammatory mediators like Arachidonic acid higher Fatty acid synthesis and fat metabolism 83 COX-2. Hemolipophosphate family, which act as Sphingolipid and glycerophosphate receptor-active mediators with complex Lysophosphatidic acid higher 34 metabolism roles in cell growth, differentiation, apoptosis and development Sphingolipid and glycerophosphate Lysophosphatidylcholine higher 34 metabolism Sphingolipid and glycerophosphate Phosphatidic acid higher 34 metabolism Sphingolipid and glycerophosphate Phosphatidylinositol lower 34 metabolism Sphingolipid and glycerophosphate Phosphatidyl choline lower 34 metabolism Sphingolipid and glycerophosphate Sphinganine higher 35 metabolism Sphingolipid and glycerophosphate Palmitoyl sphingomyelin higher 35 metabolism Sphingolipid and glycerophosphate Stearoyl sphingomyelin higher 35 metabolism Sphingolipid and glycerophosphate Sphingosine 1-phosphate lower 35 metabolism Antioxidant, resistance to lipid lower 35 peroxidation higher Biosynthesis of bile acids 61 In Lesion Synthesis of cholesterol,triglycerides Choline is a necessary part of cell growth Choline higher 21,24 and bile acids and division. Synthesis of bile acids and a small Involved in pro-inflammatory response Taurine higher 21,55,56 amount of energy supply and oxidative stress arachidonic acid LOX product that acts 5-,8-,9,11-,12- and as an effective leukocyte converting 15-hydroxyeicosatetraenoic higher Arachidonic acid metabolism 59,35 agent and has been found to be increased acid (HETE) in lesioned skin in psoriasis.

9-and higher Linoleic acid metabolism Peroxidation products of linoleic acid 35

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13-hydroxyoctadecadienoic acid (HODE) sphingolipid lower DE novo synthesis of ceramides 34,106 It induces the migration of lymphocytes and macrophages, increases the Lysophosphatidylcholine higher Low density lipoprotein oxidative stress production of pro-inflammatory 34,58 cytokines, induces oxidative stress, thereby developing inflammation. 7-, 14-, 17-hydroxydocosahexaenoic higher DHA pathway marker 35 acid (HDHA) In Urine Tetranor-12(S)-HETE higher The conversion of 12(S)-HETE to tetranor-12(S)-HETE may be a secondary product of microsomal β-oxidation Arachidonic acid metabolism 59 12(S)-HETE lower induced by skin inflammation. Therefore, it may become the potential biomarker to reflect psoriatic skin inflammation. Biosynthesis of cholesterol and Trigonelline lower 25 triglycerides Organic acid metabolism and fat Carnitine lower 25 oxidation, COX-2: Cyclic oxidase type 2; DHA: Docosahexaenoic acid.

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Supplementary Table 3: metabolism in patients with psoriasis Metabolites Changes Pathways Implication References In Peripheral blood Reduced asparagine levels may reflect the high rate of Metabolism of alanine, aspartic Asparagine lower cell renewal and chronic inflammatory state seen in 26,27 acid and glutamate psoriasis. Glutamine plays a critical role in cell protein synthesis Glutamine and glutamate Glutamine lower and growth, and in psoriasis patients may have a higher 26,83 metabolism rate of consumption due to overactive immune cells. Participate in the metabolism of Glucuronic acid higher 26 porphyrins and cholate

Synthesis of neurotransmitters higher 27 and hormones higher Urea cycle In the development of psoriasis characterized by 27,61 higher Urea cycle hyperproliferation of keratinocytes, the increased 27,61 demand for polyamines may promote the outward higher Urea cycle mobilization of the three intermediates of the urea 27,61 cycle from their synthetic sites. Keratinization of the epidermis requires scaffold Proline higher 61 Raw material for collagen proteins and supporting proteins. There are indications synthesis in skin that patients with psoriasis have a higher rate of Glycine higher 61 collagen conversion. Valine, leucine and isoleucine Valine higher 28,69,70,71 biosynthesis Cell proliferation, survival and protein synthesis) and Valine, leucine and isoleucine promote growth and proliferation of epithelial cells Isoleucine higher 28,69,70,71 biosynthesis causes asymmetric accumulation of Homocysteine higher metabolism dimethylarginine (ADMA), which leads to endothelial dysfunction, and ADMA is a potent endogenous nitric 75 Symmetric dimethyl higher Methionine metabolism oxide (NO) synthase inhibitor of the 1-arginine-NO arginine pathway. In Lesion

The increase in glutamate may be secondary to Glutamine and glutamate increased glutamine requirements during conditions of Glutamic acid higher 24,26 metabolism rapid protein synthesis and cytokine production, which are typically involved in cellular overproliferation.

Synthesis of neurotransmitters Phenylalanine metabolism is interrupted by immune Phenylalanine higher 24 and hormones activity and, therefore, the metabolite accumulates. protein in the skin could be degraded to , glutamine, and then further decomposed to Urocanic acid lower Filaggrin degradation urocanic acid, which plays an important role in 24 maintaining the integrity of the epidermal barrier and can absorb ultraviolet rays.

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It is suggested that it may be closely related to the Citrulline lower Urea cycle hyperproliferation of keratinocytes and the 24 hypersynthesis of keratin.

Speculation may be related to overexpression of Ornithine higer Urea cycle, NOS pathway 81,82 arginase-1. Arginase-1 consumes more arginine, reducing its utilization of iNOS, resulting in low levels Arginine lower Urea cycle, NOS pathway 81,82 of NO, which promotes epidermal hyperplasia.

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Supplementary Table 4: metabolism in patients with psoriasis Metabolites Changes Pathways Implication References In Peripheral blood Purine and pyrimidine nucleotide aspartic acid lower 26,27 metabolism Purine and pyrimidine nucleotide glutamine lower 26 metabolism higher Purine decomposition 27 higher Purine decomposition 27 higher Provision of carbon unit 83 Participate in the synthesis of glycine higher Provision of carbon unit 61 purines and pyrimidines in vivo histidine higher Provision of carbon unit 83 pseudouridine lower Modified nucleosides 83 It can be converted into inosine lower 83 and then into ATP for metabolism guanosine lower Nucleotide metabolism 83 cystine lower Methionine cycle Provide active methyl groups and 83 lower Methionine cycle participate in methylation 83 methionine lower Methionine cycle reaction. 83 phosphoric acid lower Nucleotide metabolism 83 Purine and pyrimidine nucleotide adenosine 5′-diphosphate higher 35 metabolism 5,6-dihydrothymine higher Purine degradation products 35 In Urine FAPy-adenine lower Purine catabolism 137 higher Purine catabolism 137

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