General Information of MET (ID: META00121)
Name 3-Hydroxybutyric acid
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(-)-3-Hydroxy-n-butyric acid; (-)-3-Hydroxybutyric acid; (3R)-3-Hydroxybutanoic acid; (3R)-3-Hydroxybutyric acid; (3R)-Hydroxybutyrate; (R)-(-)-3-Hydroxybutyric acid; (R)-(-)-b-Hydroxybutyrate; (R)-(-)-b-Hydroxybutyric acid; (R)-(-)-beta-Hydroxybutyric acid; (R)-3-Hydroxybutanoate; (R)-3-Hydroxybutanoic acid; (R)-3-Hydroxybutyrate; (R)-3-Hydroxybutyric acid; (R)-beta-Hydroxybutanoic acid; 3-D-Hydroxybutyrate; 3-D-Hydroxybutyric acid; 3-Hydroxy-n-butyric acid; 3-Hydroxybutanoic acid; 3-Hydroxybutyric acid; 3-delta-Hydroxybutyrate; 3-delta-Hydroxybutyric acid; 3R-Hydroxy-butanoate; 3R-Hydroxybutanoic acid; BHIB; D-(-)-3-Hydroxybutanoic acid; D-(-)-3-Hydroxybutyrate; D-(-)-3-Hydroxybutyric acid; D-3-Hydroxybutyrate; D-3-Hydroxybutyric acid; D-b-Hydroxybutyrate; D-b-Hydroxybutyric acid; D-beta-Hydroxybutyric acid; beta-Hydroxy-n-butyric acid; beta-Hydroxybutanoic acid; delta-(-)-3-Hydroxybutyrate; delta-3-Hydroxybutyrate; delta-3-Hydroxybutyric acid; delta-beta-Hydroxybutyrate
Source Endogenous;Fatty acyls;Food;TCM Ingredients;Microbial
Structure Type   Beta hydroxy acids and derivatives  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic acids and derivatives
Hydroxy acids and derivatives
Beta hydroxy acids and derivatives
PubChem CID
92135
HMDB ID
HMDB0000011
Formula
C4H8O3
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
C01089
ChEBI ID
17066
FooDB ID
FDB021869
ChemSpider ID
83181
Physicochemical Properties Molecular Weight 104.1 Topological Polar Surface Area 57.5
XlogP -0.5 Complexity 69.3
Heavy Atom Count 7 Rotatable Bond Count 2
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Function
3-Hydroxybutyric acid (CAS: 300-85-6), also known as beta-hydroxybutanoic acid, is a typical partial-degradation product of branched-chain amino acids (primarily valine) released from muscle for hepatic and renal gluconeogenesis. This acid is metabolized by 3-hydroxybutyrate dehydrogenase (catalyzes the oxidation of 3-hydroxybutyrate to form acetoacetate, using NAD+ as an electron acceptor). The enzyme functions in nervous tissues and muscles, enabling the use of circulating hydroxybutyrate as a fuel. In the liver mitochondrial matrix, the enzyme can also catalyze the reverse reaction, a step in ketogenesis. 3-Hydroxybutyric acid is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid, and is a ketone body. Like the other ketone bodies (acetoacetate and acetone), levels of 3-hydroxybutyrate in blood and urine are raised in ketosis. In humans, 3-hydroxybutyrate is synthesized in the liver from acetyl-CoA and can be used as an energy source by the brain when blood glucose is low. Blood levels of 3-hydroxybutyric acid levels may be monitored in diabetic patients to look for diabetic ketoacidosis. Persistent mild hyperketonemia is a common finding in newborns. Ketone bodies serve as an indispensable source of energy for extrahepatic tissues, especially the brain and lung of developing mammals. Another important function of ketone bodies is to provide acetoacetyl-CoA and acetyl-CoA for the synthesis of cholesterol, fatty acids, and complex lipids. During the early postnatal period, acetoacetate (AcAc) and beta-hydroxybutyrate are preferred over glucose as substrates for the synthesis of phospholipids and sphingolipids in accord with requirements for brain growth and myelination. Thus, during the first two weeks of postnatal development, when the accumulation of cholesterol and phospholipids accelerates, the proportion of ketone bodies incorporated into these lipids increases. On the other hand, an increased proportion of ketone bodies is utilized for cerebroside synthesis during the period of active myelination. In the lung, AcAc serves better than glucose as a precursor for the synthesis of lung phospholipids. The synthesized lipids, particularly dipalmitoylphosphatidylcholine, are incorporated into surfactant, and thus have a potential role in supplying adequate surfactant lipids to maintain lung function during the early days of life. 3-Hydroxybutyric acid is found to be associated with fumarase deficiency and medium-chain acyl-CoA dehydrogenase deficiency, which are inborn errors of metabolism. 3-Hydroxybutyric acid is a metabolite of Alcaligenes and can be produced from plastic metabolization or incorporated into polymers, depending on the species.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            Phosphoinositide lipid phosphatase (PLIP) 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 Knockout of Ptpmt1
                      Induced Change 3-Hydroxybutyric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Fatty liver disease [ICD-11: DB92]
                      Details It is reported that knockout of Ptpmt1 leads to the decrease of 3-hydroxybutyric acid levels compared with control group.
      Lyases (EC 4)
            Cystathionine gamma-lyase (CTH) 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 Knockout of Cth
                      Induced Change 3-Hydroxybutyric acid concentration: decrease (FC = 0.39)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Organic acid disorderss [ICD-11: 5C50]
                      Details It is reported that knockout of Cth leads to the decrease of 3-hydroxybutyric acid levels compared with control group.
      Oxidoreductases (EC 1)
            D-beta-hydroxybutyrate dehydrogenase (BDH1) 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 Overexpression of BDH1
                      Induced Change 3-Hydroxybutyric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that overexpression of BDH1 leads to the decrease of 3-hydroxybutyric acid levels compared with control group.
      Transferases (EC 2)
            Succinyl CoA:3-oxoacid CoA transferase (SCOT) 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 [3]
                      Introduced Variation Knockdown (shRNA) of OXCT1
                      Induced Change 3-Hydroxybutyric acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that knockdown of OXCT1 leads to the increase of 3-hydroxybutyric acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Overexpression of OXCT1
                      Induced Change 3-Hydroxybutyric acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that overexpression of OXCT1 leads to the decrease of 3-hydroxybutyric acid levels compared with control group.
References
1 Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver development. Mol Cell Biol. 2012 Jul;32(14):2685-97.
2 Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes. Oxid Med Cell Longev. 2021 Feb 13;2021:8877691.
3 Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress. Cell Res. 2016 Oct;26(10):1112-1130.

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