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Targeted Metabolomics Services

3-Hydroxy-isobutyrate

3HIB
Updated 21/12/2022

What is measured?

Synonyms: β-Hydroxyisobutyrate, 3-hydroxy-2-methylpropanoate
Method(s): GC-MS/MS (1).

What is 3-hydroxyisobutyrate?

3-Hydroxyisobutyrate (3HIB) is a catabolic intermediate of the branched-chain amino acid (BCAA), valine. 3HIB has recently been identified as a bioactive paracrine metabolite that is secreted from muscle and regulates trans-endothelial flux of fatty acids. Increased catabolic flux of BCAA may increase secretion of 3HIB from muscle, leading to increased import of fatty acid into muscle and accumulation of lipotoxic, incompletely esterified intermediates that blunt insulin signalling (2). Accordingly, elevated 3HIB in serum has been observed in individuals with diabetes, and recently to be associated with incident diabetes type 2 (3).

Indication(s)

Assessment of cardiovascular risk and risk of diabetes type 2, linked to levels of BCAA.

Specimen, collection and processing

Patient/subject: No special precaution.
Matrix: Serum or EDTA plasma.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Stable.

Transportation

Frozen, on dry ice. (for general instruction on transportation, click here)

Reported values, interpretation

Reported values: 15-25 µmol/L
Intraclass correlation coefficient (ICC): na.

Literature

1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. Jang, C., Oh, S.F., Wada, S., Rowe, G.C., Liu, L., Chan, M.C., Rhee, J., Hoshino, A., Kim, B., et al. (2016). A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 22, 421-26.
3. Arany, Z., and Neinast, M. (2018). Branched chain amino acids in metabolic disease. Curr Diab Rep 18, 76.

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Biomarkers included

Amino acids

  • Alanine
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  • Tryptophan
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  • Valine

Amino acids and catabolites

  • 2-Aminoadipic acid
  • 2-Hydroxybutyrate
  • 3-Hydroxysiobutyrate
  • a-Hydroxyglutaric acid
  • B-Alanine
  • B-Aminoisobutyrate
  • B-Hydroxy B-methylbutyric acid
  • Phenylacetylglutamine

Acylcarnities

  • BB Butyrobetaine
  • C0 Carnitine
  • C2 Acetylcarnitine
  • C3 Propionylcarnitine
  • C3-DC Malonylcarnitine
  • C4 Butyrylcarnitine
  • C4-OH Hydroxybutyrylcarnitine
  • C4-DC Succinylcarnitine
  • iC5 Isovalerylcarnitine
  • C5-DC Glutarylcarnitine
  • C5:1 Tiglylcarnitine
  • C6 Hexanoylcarnitine
  • C8 Octanoylcarnitine
  • C10 Decanoylcarnitine
  • C12 Dodecanoylcarnitine
  • C14 Tetradecanoylcarnitine
  • C14-OH Hydroxytetradecanoylcarnitine
  • C16 Hexadecanoylcarnitine
  • C16-OH Hydroxyhexadecanoylcarnitine
  • C18 Octadecanoylcarnitine
  • C18-OH Hydroxyoctadecanoylcarnitine
  • C18:1 Octadecenoylcarnitine
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TCA metabolites

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  • Fumarate
  • Isocitrate
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  • Pyruvate

Ketone bodies

  • 3-Hydroxybutyrate
  • Acetoacetate

AGEs

Biomarkers included

SCFAs

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  • Butyrate
  • Formate
  • Isobutyrate
  • Isovalerate
  • Propionate
  • Valerate
  • α-Methylbutyrate

Proteins

  • C-Reactive protein
  • Calprotectin
  • Serum Amyloid A

Others

  • Kynurenine/tryptophan ratio
  • Neopterin
  • PAr index (PLP, PL, PA)
Biomarkers included

SCFAs

  • Acetate
  • Butyrate
  • Formate
  • Isobutyrate
  • Isovalerate
  • Propionate
  • Valerate
  • α-Methylbutyrate

Indoles

  • 3-Indoxyl sulfate
  • Imidazole propionate
  • Indole-3-acetamide
  • Indole-3-acetate
  • Indole-3-aldehyde
  • Indole-3-lactate
  • Indole-3-propionate

Choline metabolites

  • Choline
  • Betaine
  • DMG
  • TMAO

Amino acid derived

  • Phenylacetylglutamine
Biomarkers included

B-vitamins, functional markers, and methyl donors

  • 4-Pyridoxic acid
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  • Pyridoxal 5-phosphate
  • Pyridoxine
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  • Thiamine monophosphate
  • Total homocysteine

Fat-soluble vitamins

  • 25-hydroxy vitamin D2
  • 25-hydroxy vitamin D3
  • α-Tocopherol (Vit. E)
  • All-trans retinol (Vit. A)
  • Phylloquinone (Vit. K1)
  • y-Tocopherol (Vit. E)

Essential amino acids

  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

Meat and fish intake

  • 1-Methylhistidine
  • 3-Methylhistidine
  • B-Alanine
  • Creatine
  • Creatinine
  • TMAO

Tobacco use and coffee intake

  • Cotinine
  • Trans-3-hydroxycotinine
  • Trigonelline

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