Bioactivity Comments

Glutamate has been described as a coagonist along with glycine at NMDA receptors [4].

Natural/Endogenous Targets
Target GluA1 GluA2 GluA3 GluA4 GluD1 GluD2 GluK1 GluK2 GluK3 GluK4 GluK5 GluN1 GluN2A GluN2B GluN2C GluN2D GluN3A GluN3B mGlu1 receptor mGlu2 receptor mGlu3 receptor mGlu4 receptor mGlu5 receptor mGlu6 receptor mGlu7 receptor mGlu8 receptor

Enzymes Catalysing Reactions with this Compound as a Substrate or Product

Enzyme EC number Reaction Reference Glutamic acid decarboxylase 1 4.1.1.15 L-glutamic acid + H+ -> GABA + CO2 Glutamic acid decarboxylase 2 4.1.1.15 L-glutamic acid + H+ -> GABA + CO2 4-aminobutyrate aminotransferase 2.6.1.19, 2.6.1.22 GABA + α-ketoglutaric acid = L-glutamic acid + 4-oxobutanoate (S)-3-amino-2-methylpropanoate + α-ketoglutaric acid = 2-methyl-3-oxopropanoate + L-glutamic acid Tyrosine aminotransferase 2.6.1.5 L-tyrosine + α-ketoglutaric acid -> 4-hydroxyphenylpyruvic acid + L-glutamic acid

Transporters Moving this Compound Across a Lipid Membrane

Transporter EC number Reaction Reference Excitatory amino acid transporter 1 Excitatory amino acid transporter 2 Excitatory amino acid transporter 3 Excitatory amino acid transporter 4 Excitatory amino acid transporter 5 Cation-chloride cotransporter 9 Sialin 13 AGC1 AGC2 Mitochondrial glutamate carrier 2 Mitochondrial glutamate carrier 1 Alanine/serine/cysteine transporter 2 Vesicular glutamate transporter 1 Vesicular glutamate transporter 2 Vesicular glutamate transporter 3 SLC26A7 SLC26A9 Sodium-coupled neutral amino acid transporter 3 7

Selectivity at GPCRs
Key to terms and symbols		Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference mGlu3 receptor Hs Agonist Full agonist 7.4 pKi - 9 ⤷ pKi 7.4 [9] mGlu1 receptor Rn Agonist Full agonist 6.4 – 6.5 pKi - 11,14 ⤷ pKi 6.4 – 6.5 [11,14] mGlu3 receptor Rn Agonist Full agonist 6.4 pKi - 16 ⤷ pKi 6.4 [16] mGlu2 receptor Rn Agonist Full agonist 5.4 – 5.9 pKi - 2,6 ⤷ pKi 5.4 – 5.9 [2,6] mGlu4 receptor Rn Agonist Full agonist 4.9 – 5.5 pKi - 1,8,17-18 ⤷ pKi 4.9 – 5.5 [1,8,17-18] mGlu2 receptor Hs Agonist Full agonist 4.9 pKi - 9 ⤷ pKi 4.9 [9] mGlu7 receptor Hs Agonist Full agonist 3.1 pKi - 19 ⤷ pKi 3.1 [19] mGlu3 receptor Hs Agonist Agonist 5.3 – 5.4 pEC50 - 15 ⤷ pEC50 5.3 – 5.4 [15] mGlu5 receptor Hs Agonist Agonist 5.0 – 5.5 pEC50 - 15 ⤷ pEC50 5.0 – 5.5 [15] mGlu8 receptor Hs Agonist Agonist 4.9 – 5.6 pEC50 - 15 ⤷ pEC50 4.9 – 5.6 [15] mGlu6 receptor Hs Agonist Full agonist 5.2 pEC50 - 10 ⤷ pEC50 5.2 [10] mGlu4 receptor Hs Agonist Agonist 4.7 – 5.5 pEC50 - 15 ⤷ pEC50 4.7 – 5.5 [15] mGlu2 receptor Hs Agonist Agonist 4.7 – 5.4 pEC50 - 15 ⤷ pEC50 4.7 – 5.4 [15] mGlu1 receptor Hs Agonist Agonist 4.8 – 5.0 pEC50 - 15 ⤷ pEC50 4.8 – 5.0 [15] mGlu6 receptor Hs Agonist Agonist 4.8 pEC50 - 15 ⤷ pEC50 4.8 [15] mGlu6 receptor Rn Agonist Full agonist 4.4 pEC50 - 3 ⤷ pEC50 4.4 [3] mGlu7 receptor Hs Agonist Agonist 3.0 pEC50 - 15 ⤷ pEC50 3.0 [15] mGlu5 receptor Rn Agonist Full agonist 6.1 pIC50 - 14 ⤷ pIC50 6.1 [14] mGlu8 receptor Hs Agonist Full agonist 5.0 – 5.7 pIC50 - 12,20 ⤷ pIC50 5.0 – 5.7 [12,20]

Additional information and targets (data relate to human unless otherwise stated)
Description	Data	Reference
Endogenous substrates at Alanine/serine/cysteine transporter 2	L-alanine = L-serine = L-cysteine (low Vmax) = L-threonine = L-glutamine = L-asparagine >> L-methionine ≅ glycine ≅ L-leucine > L-valine > L-glutamic acid (enhanced at low pH)
Endogenous substrates at Vesicular glutamate transporter 1	L-glutamic acid > D-glutamic acid
Endogenous substrates at Vesicular glutamate transporter 2	L-glutamic acid > D-glutamic acid
Endogenous substrates at Vesicular glutamate transporter 3	L-glutamic acid > D-glutamic acid
Substrates at Sodium-coupled neutral amino acid transporter 3	L-histidine , L-glutamine > L-asparagine, L-alanine > L-glutamic acid	7
Amino-acid rank order of potency at CaS receptor	L-phenylalanine, L-tryptophan, L-histidine > L-alanine > L-serine, L-proline, L-glutamic acid > L-aspartic acid (not L-lysine, L-arginine, L-leucine and L-isoleucine)	5
Substrates at SLC26A9	I- > Br- > NO3- > Cl- > L-glutamic acid
Substrates at SLC26A7	NO3- >> Cl- = Br- = I- > SO42- = L-glutamic acid

Targets where the ligand is described in the comment field
Target	Comment
Folate hydrolase (prostate-specific membrane antigen) 1	Folate hydrolase is also known as NAALADase as it is responsible for the hydrolysis of N-acetaspartylglutamate to form N-acetylaspartate and L-glutamate (L-glutamic acid). In the gut, the enzyme assists in the assimilation of folate by hydrolysing dietary poly-gamma-glutamylfolate. The enzyme is highly expressed in the prostate, and its expression is up-regulated in cancerous tissue. A tagged version of the antibody capromab has been used for imaging purposes.

Ligand mentioned in the following text fields
Metabotropic glutamate receptors overview
SLC17 phosphate and organic anion transporter family overview
Taste 1 receptors overview
SLC7 family comments