Supplementary Table 1: Glucose metabolism in patients with psoriasis
Metabolites Changes Pathways Implication References
In Peripheral blood
α-ketoglutaric acid higher Tricarboxylic acid cycle
α-Ketoglutarate acts as a citric acid cycle intermediate and is converted to glutamic acid, which downstream produces proline for collagen synthesis
26
Lactic acid higher Glycolysis and pyruvate metabolism
The glycolytic activity of psoriasis patients is greatly enhanced and can provide a favorable microenvironment for
keratinogenic cell proliferation
27
Aspartic acid higher Mitochondria oxidized
respiratory chain 26,27
Glutamic acid higher Mitochondria oxidized respiratory chain
The increase in glutamate may be secondary to increased glutamine requirements during conditions of rapid protein synthesis and cytokine production
24,26
Valine higher Valine, leucine and isoleucine biosynthesis
Excess BCAA may worsen insulin resistance, which leads to the accumulation of inflammatory cytokines
28,69,70,71,
Isoleucine higher 28,69,70,71,
Succinate lower Tricarboxylic acid cycle 83
In Lesion
Myoinositol lower
Anaerobic oxidation of glucose;
Synthesis of
phosphatidylinositol by gluconeogenesis
21,24
Glucose lower Glycometabolism 21
Lactic acid lower Glycolysis and pyruvate metabolism
The reduction of lactic acid in local lesions is most likely due to metabolic changes in sweat glands and keratinocytes or obstruction of sweat ducts.
24
In Urine
Citrate lower Tricarboxylic acid cycle 25
Alanine lower Alanine glucose cycle 25
Methylsuccinate lower Tricarboxylic acid cycle 25
Lactose
6-phosphate higher
Anaerobic fermentation of glucose
137
Oxoglutaric acid lower 137
Glucosamine
6-sulfate lower 137
γ-Hydroxybutyric
acid lower
Oxidation to succinic acid and then involved in the tricarboxylic acid cycle
137
BCAAs: Branched-chain amino acids.
- 2 -
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 Urea cycle 27
Cholesterol higher Lipid metabolism and bile acid
synthesis 83
Arachidonic acid higher Fatty acid synthesis and fat metabolism Produce inflammatory mediators like
COX-2. 83
Lysophosphatidic acid higher Sphingolipid and glycerophosphate metabolism
Hemolipophosphate family, which act as receptor-active mediators with complex roles in cell growth, differentiation, apoptosis and development
34
Lysophosphatidylcholine higher Sphingolipid and glycerophosphate
metabolism 34
Phosphatidic acid higher Sphingolipid and glycerophosphate
metabolism 34
Phosphatidylinositol lower Sphingolipid and glycerophosphate
metabolism 34
Phosphatidyl choline lower Sphingolipid and glycerophosphate
metabolism 34
Sphinganine higher Sphingolipid and glycerophosphate
metabolism 35
Palmitoyl sphingomyelin higher Sphingolipid and glycerophosphate
metabolism 35
Stearoyl sphingomyelin higher Sphingolipid and glycerophosphate
metabolism 35
Sphingosine 1-phosphate lower Sphingolipid and glycerophosphate
metabolism 35
Glutathione lower Antioxidant, resistance to lipid
peroxidation 35
Glycine higher Biosynthesis of bile acids 61
In Lesion
Choline higher Synthesis of cholesterol,triglycerides and bile acids
Choline is a necessary part of cell growth
and division. 21,24
Taurine higher Synthesis of bile acids and a small amount of energy supply
Involved in pro-inflammatory response
and oxidative stress 21,55,56
5-,8-,9,11-,12- and 15-hydroxyeicosatetraenoic acid (HETE)
higher Arachidonic acid metabolism
arachidonic acid LOX product that acts as an effective leukocyte converting agent and has been found to be increased in lesioned skin in psoriasis.
59,35
9-and higher Linoleic acid metabolism Peroxidation products of linoleic acid 35
13-hydroxyoctadecadienoic acid (HODE)
sphingolipid lower DE novo synthesis of ceramides 34,106
Lysophosphatidylcholine higher Low density lipoprotein oxidative stress
It induces the migration of lymphocytes and macrophages, increases the production of pro-inflammatory cytokines, induces oxidative stress, thereby developing inflammation.
34,58
7-, 14-,
17-hydroxydocosahexaenoic acid (HDHA)
higher DHA pathway marker 35
In Urine
Tetranor-12(S)-HETE higher
Arachidonic acid metabolism
The conversion of 12(S)-HETE to tetranor-12(S)-HETE may be a secondary product of microsomal β-oxidation induced by skin inflammation. Therefore, it may become the potential biomarker to reflect psoriatic skin inflammation.
12(S)-HETE lower 59
Trigonelline lower Biosynthesis of cholesterol and
triglycerides 25
Carnitine lower Organic acid metabolism and fat
oxidation, 25
COX-2: Cyclic oxidase type 2; DHA: Docosahexaenoic acid.
- 4 -
Supplementary Table 3: Amino acid metabolism in patients with psoriasis
Metabolites Changes Pathways Implication References
In Peripheral blood
Asparagine lower Metabolism of alanine, aspartic acid and glutamate
Reduced asparagine levels may reflect the high rate of cell renewal and chronic inflammatory state seen in psoriasis.
26,27
Glutamine lower Glutamine and glutamate metabolism
Glutamine plays a critical role in cell protein synthesis and growth, and in psoriasis patients may have a higher rate of consumption due to overactive immune cells.
26,83
Glucuronic acid higher Participate in the metabolism of
porphyrins and cholate 26
Phenylalanine higher Synthesis of neurotransmitters
and hormones 27
Citrulline higher Urea cycle In the development of psoriasis characterized by hyperproliferation of keratinocytes, the increased demand for polyamines may promote the outward mobilization of the three intermediates of the urea cycle from their synthetic sites.
27,61
Ornithine higher Urea cycle 27,61
Arginine higher Urea cycle 27,61
Proline higher
Raw material for collagen synthesis in skin
Keratinization of the epidermis requires scaffold proteins and supporting proteins. There are indications that patients with psoriasis have a higher rate of collagen conversion.
61
Glycine higher 61
Valine higher Valine, leucine and isoleucine
biosynthesis Cell proliferation, survival and protein synthesis) and promote growth and proliferation of epithelial cells
28,69,70,71
Isoleucine higher Valine, leucine and isoleucine
biosynthesis 28,69,70,71
Homocysteine higher Methionine metabolism
Homocysteine causes asymmetric accumulation of dimethylarginine (ADMA), which leads to endothelial dysfunction, and ADMA is a potent endogenous nitric oxide (NO) synthase inhibitor of the 1-arginine-NO pathway.
75 Symmetric dimethyl
arginine higher Methionine metabolism
In Lesion
Glutamic acid higher Glutamine and glutamate metabolism
The increase in glutamate may be secondary to increased glutamine requirements during conditions of rapid protein synthesis and cytokine production, which are typically involved in cellular overproliferation.
24,26
Phenylalanine higher Synthesis of neurotransmitters and hormones
Phenylalanine metabolism is interrupted by immune activity and, therefore, the metabolite accumulates. 24
Urocanic acid lower Filaggrin degradation
Filaggrin protein in the skin could be degraded to histidine, glutamine, and then further decomposed to urocanic acid, which plays an important role in maintaining the integrity of the epidermal barrier and can absorb ultraviolet rays.
24
Citrulline lower Urea cycle
It is suggested that it may be closely related to the hyperproliferation of keratinocytes and the hypersynthesis of keratin.
24
Ornithine higer Urea cycle, NOS pathway Speculation may be related to overexpression of arginase-1. Arginase-1 consumes more arginine, reducing its utilization of iNOS, resulting in low levels of NO, which promotes epidermal hyperplasia.
81,82
Arginine lower Urea cycle, NOS pathway 81,82
- 6 -
Supplementary Table 4: Nucleotide metabolism in patients with psoriasis
Metabolites Changes Pathways Implication References
In Peripheral blood
aspartic acid lower Purine and pyrimidine nucleotide
metabolism 26,27
glutamine lower Purine and pyrimidine nucleotide
metabolism 26
Uric acid higher Purine decomposition 27
hypoxanthine higher Purine decomposition 27
serine higher Provision of carbon unit
Participate in the synthesis of purines and pyrimidines in vivo
83
glycine higher Provision of carbon unit 61
histidine higher Provision of carbon unit 83
pseudouridine lower Modified nucleosides 83
inosine lower It can be converted into nucleotides
and then into ATP for metabolism 83
guanosine lower Nucleotide metabolism 83
cystine lower Methionine cycle Provide active methyl groups and
participate in methylation reaction.
83
cysteine lower Methionine cycle 83
methionine lower Methionine cycle 83
phosphoric acid lower Nucleotide metabolism 83
adenosine 5′-diphosphate higher Purine and pyrimidine nucleotide
metabolism 35
5,6-dihydrothymine higher Purine degradation products 35
In Urine
FAPy-adenine lower Purine catabolism 137
Inosinic acid higher Purine catabolism 137
