General Information of MET (ID: META00054)
Name Lactic acid
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(+)-Lactate; (+)-Lactic acid; (S)-(+)-2-Hydroxypropanoate; (S)-(+)-2-Hydroxypropanoic acid; (S)-(+)-Lactate; (S)-(+)-Lactic acid; (S)-2-Hydroxy-propanoate; (S)-2-Hydroxy-propanoic acid; (S)-2-Hydroxypropanoate; (S)-2-Hydroxypropanoic acid; (S)-2-Hydroxypropionate; (S)-2-Hydroxypropionic acid; (S)-Lactate; (S)-Lactic acid; (alpha)-Lactate; (alpha)-Lactic acid; 1-Hydroxyethane 1-carboxylate; 1-Hydroxyethane 1-carboxylic acid; 1-Hydroxyethanecarboxylate; 1-Hydroxyethanecarboxylic acid; 2 Hydroxypropanoic acid; 2 Hydroxypropionic acid; 2-Hydroxypropanoate; 2-Hydroxypropanoic acid; 2-Hydroxypropionate; 2-Hydroxypropionic acid; Ammonium lactate; D Lactic acid; D-Lactate; D-Lactic acid; L Lactic acid; L-(+)- Lactic acid; L-(+)-Lactate; L-(+)-Lactic acid; L-(+)-a-Hydroxypropionate; L-(+)-a-Hydroxypropionic acid; L-(+)-alpha-Hydroxypropionic acid; L-2-Hydroxypropanoate; L-2-Hydroxypropanoic acid; L-Lactate; L-Lactic acid; L-Milchsaeure; Lactate; Lactate, ammonium; Lactic acid; Milk acid; Sarcolactic acid; a-Hydroxypropanoate; a-Hydroxypropanoic acid; a-Hydroxypropionate; a-Hydroxypropionic acid; alpha-Hydroxypropanoate; alpha-Hydroxypropanoic acid; alpha-Hydroxypropionate; alpha-Hydroxypropionic acid
Source Endogenous;Escherichia Coli Metabolite;Yeast Metabolite;Food;Drug;Agricultural Chemicals;Toxins/Pollutant;Cosmetic;Microbial
Structure Type   Alpha hydroxy acids and derivatives  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic acids and derivatives
Hydroxy acids and derivatives
Alpha hydroxy acids and derivatives
PubChem CID
107689
HMDB ID
HMDB0000190
Formula
C3H6O3
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00186
ChEBI ID
422
FooDB ID
FDB003294
ChemSpider ID
96860
METLIN ID
5205
Physicochemical Properties Molecular Weight 90.08 Topological Polar Surface Area 57.5
XlogP -0.7 Complexity 59.1
Heavy Atom Count 6 Rotatable Bond Count 1
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Function
Lactic acid is an organic acid. It is a chiral molecule, consisting of two optical isomers, L-lactic acid and D-lactic acid, with the L-isomer being the most common in living organisms. Lactic acid plays a role in several biochemical processes and is produced in the muscles during intense activity. In animals, L-lactate is constantly produced from pyruvate via the enzyme lactate dehydrogenase (LDH) in a process of fermentation during normal metabolism and exercise. It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal. This is governed by a number of factors, including monocarboxylate transporters, lactate concentration, the isoform of LDH, and oxidative capacity of tissues. The concentration of blood lactate is usually 1-2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion. There are some indications that lactate, and not glucose, is preferentially metabolized by neurons in the brain of several mammalian species, including mice, rats, and humans. Glial cells, using the lactate shuttle, are responsible for transforming glucose into lactate, and for providing lactate to the neurons. Lactate measurement in critically ill patients has been traditionally used to stratify patients with poor outcomes. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms adapt in many different ways, up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow tissues and cells to revert to a normal state, as long as the oxygen machinery (i.e. mitochondria) is intact. Conversely, once the mitochondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may, therefore, be viewed as an early marker of a potentially reversible state. When present in sufficiently high levels, lactic acid can act as an oncometabolite, an immunosuppressant, an acidogen, and a metabotoxin. An oncometabolite is a compound that promotes tumor growth and survival. An immunosuppressant reduces or arrests the activity of the immune system. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of lactic acid are associated with at least a dozen inborn errors of metabolism, including 2-methyl-3-hydroxybutyryl CoA dehydrogenase deficiency, biotinidase deficiency, fructose-1,6-diphosphatase deficiency, glycogen storage disease type 1A (GSD1A) or Von Gierke disease, glycogenosis type IB, glycogenosis type IC, glycogenosis type VI, Hers disease, lactic acidemia, Leigh syndrome, methylmalonate semialdehyde dehydrogenase deficiency, pyruvate decarboxylase E1 component deficiency, pyruvate dehydrogenase complex deficiency, pyruvate dehydrogenase deficiency, and short chain acyl CoA dehydrogenase deficiency (SCAD deficiency). Locally high concentrations of lactic acid or lactate are found near many tumors due to the upregulation of lactate dehydrogenase. Lactic acid produced by tumors through aerobic glycolysis acts as an immunosuppressant and tumor promoter. Indeed, lactic acid has been found to be a key player or regulator in the development and malignant progression of a variety of cancers. A number of studies have demonstrated that malignant transformation is associated with an increase in aerobic cellular lactate excretion. Lactate concentrations in various carcinomas (e.g. uterine cervix, head and neck, colorectal region) at first diagnosis of the disease, can be relatively low or extremely high (up to 40 mol/g) in different individual tumors or within the same lesion. High molar concentrations of lactate are correlated with a high incidence of distant metastasis. Low lactate tumors (< median of approximately 8 mol/g) are associated with both an overall longer and disease-free survival compared to high lactate lesions (lactate > approximately 8 mol/g). Lactate-induced secretion of hyaluronan by tumor-associated fibroblasts creates a milieu favourable for cell migration and metastases. An acidic environment (pH 6-6.5), which is common in many tumors, allows tumor cells to evade the immune response, and therefore allows them to grow unchecked. Locally high concentrations of lactic acid are known to markedly impede the function of normal immune cells and will lead to a loss of T-cell function of human tumor-infiltrating lymphocytes. Lactic acid is also an organic acid and acts as a general acidogen. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, kidney abnormalities, liver damage, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. Lactic acid is also a microbial metabolite, urinary lactic acid is produced by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterobacter, Acinetobacter, Proteus mirabilis, Citrobacter frundii, Enterococcus faecalis, Streptococcus group B, Staphylococcus saprophyticus , Bacillus, Corynebacterium, Rhizopus and Saccharomyces cerevisiae.
Regulatory Network
Full List of Protein(s) Regulated by This Metabolite
      Dicarboxylate/amino acid:cation symporter (DAACS)
            Alanine/cysteine transporter 2 (SLC1A5) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change SLC1A5 protein expression levels: increase (FC = 1.6)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of SLC1A5 protein expression compared with control group.
      Hydrolases (EC 3)
            L-glutamine amidohydrolase (GLS) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change GLS protein expression levels: increase (FC = 1.6)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of GLS protein expression compared with control group.
      Transcription factor (TF)
            Hypoxia-inducible factor 1-alpha (HIF1A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change HIF1A protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of HIF1A protein expression compared with control group.
            Hypoxia-inducible factor 2-alpha (EPAS1) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change EPAS1 protein expression levels: increase (FC = 1.8)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of EPAS1 protein expression compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change EPAS1 mRNA levels: increase (FC = 1.8)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of EPAS1 mRNA levels compared with control group.
            Myc proto-oncogene protein (MYC) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change MYC protein expression levels: increase (FC = 1.3)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of MYC protein expression compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Lactic acid addition (6 hours)
                      Induced Change MYC mRNA levels: increase (FC = 1.3)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that lactic acid addition causes the increase of MYC mRNA levels compared with control group.
Full List of Protein(s) Regulating This Metabolite
      Anion exchanger (AE)
            Sodium bicarbonate cotransporter (NBCE1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Overexpression of Slc4a4
                      Induced Change Lactic acid concentration: decrease (FC = 0.37)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Slc4a4 leads to the decrease of lactic acid levels compared with control group.
      GPCR rhodopsin (GPCR-1)
            Orexin receptor type 1 (HCRTR1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Inhibition (SB334867) of HCRTR1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that inhibition of HCRTR1 leads to the increase of lactic acid levels compared with control group.
      Growth factor (GF)
            Transforming growth factor beta 1 (TGFB1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Recombinant protein addition of TGFB1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Brain cancer [ICD-11: 2A00]
                      Details It is reported that recombinant protein addition of TGFB1 leads to the increase of lactic acid levels compared with control group.
      Hydrolases (EC 3)
            Extracellular sulfatase Sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Knockout of Sulf1
                      Induced Change Lactic acid concentration: increase (FC = 1.22)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockout of Sulf1 leads to the increase of lactic acid levels compared with control group.
            Leukotriene-C4 hydrolase (GGT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Knockdown (siRNA) of GGT1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Renal cell carcinoma [ICD-11: 2C90]
                      Details It is reported that knockdown of GGT1 leads to the increase of lactic acid levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Lactic acid concentration: increase (FC = 1.5)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the increase of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Overexpression of SULF1
                      Induced Change Lactic acid concentration: decrease (FC = 0.79)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that overexpression of SULF1 leads to the decrease of lactic acid levels compared with control group.
      Mitochondrial pyruvate carrier (MPC)
            Pyruvate carrier 1 (MPC1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Overexpression of Mpc1
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that overexpression of Mpc1 leads to the decrease of lactic acid levels compared with control group.
      Monocarboxylate porter (MNP)
            Monocarboxylate transporter 1 (SLC16A1) Click to Show/Hide the Full List of Regulating Pair(s):   5 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Chloromercuribenzenesulfonic acid (pCMBS)) of SLC16A1
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A1 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Diclofenac) of SLC16A1
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A1 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Chloromercuribenzenesulfonic acid (pCMBS)) of SLC16A1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A1 leads to the increase of lactic acid levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (AR-C155858) of SLC16A1
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A1 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (AR-C155858) of SLC16A1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A1 leads to the increase of lactic acid levels compared with control group.
            Monocarboxylate transporter 4 (SLC16A3) Click to Show/Hide the Full List of Regulating Pair(s):   5 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Diclofenac) of SLC16A3
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A3 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Chloromercuribenzenesulfonic acid (pCMBS)) of SLC16A3
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A3 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (Chloromercuribenzenesulfonic acid (pCMBS)) of SLC16A3
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A3 leads to the increase of lactic acid levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (AR-C155858) of SLC16A3
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A3 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Knockout of SLC16A3
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that knockout of SLC16A3 leads to the decrease of lactic acid levels compared with control group.
            Solute carrier family 16 member 7 (SLC16A7) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Knockout of SLC16A7
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that knockout of SLC16A7 leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [8]
                      Introduced Variation Inhibition (AR-C155858) of SLC16A7
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that inhibition of SLC16A7 leads to the increase of lactic acid levels compared with control group.
      Oxidoreductases (EC 1)
            Alcohol dehydrogenase iron 1 (ADHFE1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [9]
                      Introduced Variation Overexpression of ADHFE1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that overexpression of ADHFE1 leads to the increase of lactic acid levels compared with control group.
            Glutamate-cysteine ligase modifier (GCLM) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [10]
                      Introduced Variation Knockout of Gclm
                      Induced Change Lactic acid concentration: decrease (FC = 0.67)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Metabolic liver disease [ICD-11: 5C90]
                      Details It is reported that knockout of Gclm leads to the decrease of lactic acid levels compared with control group.
            Isocitrate dehydrogenase NAD 3 alpha (IDH3A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [11]
                      Introduced Variation Knockdown (siRNA) of IDH3A
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lung cancer [ICD-11: 2C25]
                      Details It is reported that knockdown of IDH3A leads to the decrease of lactic acid levels compared with control group.
      Pore-forming PNC peptide (PNC)
            Cellular tumor antigen p53 (TP53) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [12]
                      Introduced Variation Knockout of TP53
                      Induced Change Lactic acid concentration: increase (Log2 FC=1.36)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockout of TP53 leads to the increase of lactic acid levels compared with control group.
      Sugar transporter (ST)
            Facilitated glucose transporter 1 (SLC2A1A) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation Downregulation of slc2a1a caused by Yap loss-of-function mutation
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that downregulation of slc2a1a caused by Yap loss-of-function mutation leads to the decrease of lactic acid levels compared with control group.
      Transcriptional coactivator (TC)
            Nuclear receptor coactivator 2 (NCOA2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [14]
                      Introduced Variation Knockdown (siRNA) of NCOA2
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Uterine cancer [ICD-11: 2C76]
                      Details It is reported that knockdown of NCOA2 leads to the decrease of lactic acid levels compared with control group.
            Transcriptional coactivator YAP1 (yap1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [13]
                      Introduced Variation Decrease of Yap mRNA caused by Yap loss-of-function mutation
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that decrease of Yap mRNA caused by Yap loss-of-function mutation leads to the decrease of lactic acid levels compared with control group.
      Transferases (EC 2)
            Mercaptopyruvate sulfurtransferase (MPST) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [15]
                      Introduced Variation Knockdown (siRNA) of MPST
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockdown of Mpst leads to the increase of lactic acid levels compared with control group.
            NAD-dependent protein deacetylase sirtuin-1 (SIRT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [15]
                      Introduced Variation Knockdown (siRNA) of MPST
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockdown of Mpst leads to the increase of lactic acid levels compared with control group.
            Pyridoxal kinase (PDXK) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [16]
                      Introduced Variation Knockout (CRISPR/Cas9 sgRNA) of Pdxk
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute myeloid leukaemia [ICD-11: 2A60]
                      Details It is reported that knockout of Pdxk leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [16]
                      Introduced Variation Knockout (CRISPR/Cas9 sgRNA) of PDXK
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute myeloid leukaemia [ICD-11: 2A60]
                      Details It is reported that knockout of PDXK leads to the decrease of lactic acid levels compared with control group.
            Pyruvate kinase M2 (PKM) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [17]
                      Introduced Variation Knockdown (shRNA) of PKM
                      Induced Change Lactic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that knockdown of PKM leads to the decrease of lactic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [18]
                      Introduced Variation Knockdown (shRNA) of Pkm
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lung cancer [ICD-11: 2C25]
                      Details It is reported that knockdown of Pkm leads to the increase of lactic acid levels compared with control group.
            Transketolase-like protein 1 (TKTL1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [19]
                      Introduced Variation Overexpression of TKTL1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Head and neck squamous cell carcinoma [ICD-11: 2D60]
                      Details It is reported that overexpression of TKTL1 leads to the increase of lactic acid levels compared with control group.
      Zinc finger protein (ZIN)
            Protein snail homolog 1 (SNAI1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [20]
                      Introduced Variation Knockdown (shRNA) of SNAI1
                      Induced Change Lactic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Breast cancer [ICD-11: 2C60]
                      Details It is reported that knockdown of Snai1 leads to the increase of lactic acid levels compared with control group.
References
1 Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72-83.
2 Inhibition of monocarboxylate transporter by N-cyanosulphonamide S0859. Eur J Pharmacol. 2015 Sep 5;762:344-9.
3 Orexin A affects HepG2 human hepatocellular carcinoma cells glucose metabolism via HIF-1-dependent and -independent mechanism. PLoS One. 2017 Sep 8;12(9):e0184213.
4 TGF-1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells. FEBS J. 2017 Oct;284(20):3437-3454.
5 HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer. Oncotarget. 2015 Oct 20;6(32):33705-19.
6 Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma. Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6274-E6282.
7 A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014 Nov 6;56(3):400-13.
8 Monocarboxylate transporter 4 (MCT4) is a high affinity transporter capable of exporting lactate in high-lactate microenvironments. J Biol Chem. 2019 Dec 27;294(52):20135-20147.
9 ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming. J Clin Invest. 2018 Jan 2;128(1):323-340.
10 Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chem Biol Interact. 2019 Apr 25;303:1-6.
11 Effect of IDH3a on glucose uptake in lung adenocarcinoma: A pilot study based on [ 18 F]FDG. Cancer Med. 2019 Sep;8(11):5341-5351.
12 Integrative omics analysis of p53-dependent regulation of metabolism. FEBS Lett. 2018 Feb;592(3):380-393.
13 Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. EMBO J. 2018 Nov 15;37(22):e100294.
14 Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. Sci Rep. 2018 Sep 3;8(1):13134.
15 3-Mercaptopyruvate sulfurtransferase disruption in dermal fibroblasts facilitates adipogenic trans-differentiation. Exp Cell Res. 2019 Dec 15;385(2):111683.
16 Vitamin B6 Addiction in Acute Myeloid Leukemia. Cancer Cell. 2020 Jan 13;37(1):71-84.e7.
17 Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature. 2012 Nov 15;491(7424):458-462.
18 The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008 Mar 13;452(7184):230-3.
19 TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res. 2010 Feb 1;16(3):857-66.
20 Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress. Nat Commun. 2017 Feb 8;8:14374.

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