Glutaric acid (GA) at 1 and 2 mM was able to decrease TRAP readings in a dose-dependent manner by up to 28% (β=0.77; P<0.001). Furthermore, it was confirmed that there is a substantial negative association (β=0.81; P<0.001) between chemiluminescence and TRAP. Although glutaric acid severely reduced (up to 46%) the activity of GPx even at lower concentrations (0.5 mM), it had no effect on the activity of Cat or SOD. At as little as 0.05 mM, this metabolite was shown to block this activity in a dose-dependent manner [1].

---

In rat cortical brain slices, perfusion with 1 mM glutaric acid evoked a significant capillary constriction near pericyte somata, with a 16% reduction in capillary diameter after 25 minutes (p=0.04, n=10) and a 23% reduction after 1 hour of exposure in fixed slices (p=0.0006). This constriction is predicted to increase capillary resistance by a factor of 1.43 and reduce blood flow by 30% according to Poiseuille’s law. [3]
In primary cultured rat brain pericytes, exposure to 5 mM glutaric acid for 2 hours did not induce morphological changes characteristic of contraction (reduction of soma and nuclei size, emergence of cellular processes), unlike 100 μM ATP which significantly increased the percentage of contracted cells (p=0.0004). Glutaric acid (5 mM for 24 hours) did not affect pericyte viability as assessed by SRB assay, nor did it alter cell morphology, actin filament arrangement, or PDGFRβ expression. [3]
Conditioned medium from astrocytes treated with 5 mM glutaric acid (CM-GA) delayed pericyte migration in a scratch wound assay, resulting in significantly larger cell-free areas at 24 and 48 hours compared to control conditioned medium (CM-C) (p=0.01 and p=0.005, respectively). This effect was not due to reduced proliferation, as BrdU incorporation was similar (52-58% in all groups). Direct treatment of pericytes with 5 mM glutaric acid did not significantly affect scratch closure. [3]
Astrocyte conditioned medium from glutaric acid-treated cells (CM-GA) caused morphological changes in cultured pericytes resembling contraction, but the increase in contracted cells was similar to that induced by control conditioned medium (CM-C). Both CM-C and CM-GA significantly increased the percentage of contracted pericytes compared to vehicle (p=0.0002 and p<0.0001). [3]
Analysis of astrocyte secretome revealed elevated levels of several cytokines in CM-GA compared to CM-C, including TIMP-1, VEGF-A, ICAM-1, CINC-1, LIX, MCP-1, MIP3, and L-selectin. [3]

For pericyte contraction assessment, confluent second-passage pericytes were incubated with 5 mM glutaric acid (pH 7.4), 100 μM ATP (positive control), or vehicle for 2 hours at 37°C with 5% CO2. Cells were then fixed with 4% paraformaldehyde, and the percentage of contracted cells (defined by retraction of cell body, emergence of processes, and smaller nuclei) was evaluated relative to Hoechst 33342-stained nuclei. [3]
For pericyte viability, 10,000-20,000 pericytes per well in 96-well plates were grown to confluence and incubated with 5 mM glutaric acid, conditioned media, or vehicle for 24 hours. Cells were fixed with 10% trichloroacetic acid, stained with sulforhodamine B (0.4%), and optical density was measured at 565 nm and background at 690 nm. [3]
For pericyte migration (scratch wound assay), confluent second-passage pericytes were manually scratched with a pipette tip, detached cells removed, and cultures exposed to 5 mM glutaric acid, conditioned medium from control or glutaric acid-treated astrocytes (CM-C or CM-GA, 1:1 dilution), or vehicle. Images were taken at 0, 24, and 48 hours, and cell-free areas were measured. In some experiments, 40 μM BrdU was added to assess proliferation. BrdU-positive cells were detected by immunocytochemistry after DNA denaturation with 2N HCl. [3]
For astrocyte conditioned medium preparation, astrocytes grown to confluence in T75 flasks were treated with 5 mM glutaric acid or PBS for 24 hours, then incubated in serum-free DMEM for 24 hours. Conditioned medium was collected, centrifuged, concentrated using a 3000 nominal molecular weight limit membrane, and protein content quantified. Cytokine levels were assessed using a rat cytokine antibody array; spots were detected by chemiluminescence and integrated density measured with ImageJ. [3]
For immunocytochemistry, pericytes were fixed with 4% PFA, permeabilized with 0.1% Triton X-100, blocked with 5% BSA, and incubated with anti-αSMA (1:100), anti-PDGFRβ (1:100), or anti-NG2 (1:250) overnight at 4°C, followed by Alexa Fluor-conjugated secondary antibodies (1:500). Actin filaments were visualized with TRITC-conjugated phalloidin (1:250). Nuclei were stained with Hoechst 33342. [3]

No animal protocols involving glutaric acid administration as a drug are described. Brain slice preparation from postnatal day 21 rats is described for ex vivo experiments: coronal cortical slices (240-300 μm thick) were prepared in ice-cold oxygenated solution containing N-methyl-D-glucamine chloride, KCl, NaHCO3, MgCl2, NaH2PO4, glucose, CaCl2, HEPES, sodium ascorbate, sodium pyruvate, and kynurenic acid, then recovered in artificial cerebrospinal fluid. [3] For experiments involving glutaric acid, slices were perfused with aCSF containing 1 mM glutaric acid. [3]

Metabolism / Metabolites
Compared to glutaryl-CoA (COA), rat liver mitochondria metabolize glutaric acid very slowly. Glutaryl-CoA dehydrogenase catalyzes the stoichiometric conversion of glutaryl-CoA into 1 mole of carbon dioxide and 1 mole of crotonyl-CoA or its intermediate metabolites, yielding approximately 44-fold and 100-fold purifications from bovine liver and kidney mitochondria, respectively. The Km value of glutaryl-CoA is 3.3 μM.

---

Toxicity Summary
Glutamic acid accumulation in the body has been proven toxic. In glutamateuria, the degree of glutamate accumulation ranges from mild or intermittent elevation of urinary glutamate to severe organic aciduria. Type 1 glutamateuria is an autosomal recessive genetic disorder caused by a deficiency of mitochondrial glutaryl-CoA dehydrogenase, an enzyme involved in the metabolism of lysine, hydroxylysine, and tryptophan. Interactions Lithium chloride (1.15 g) or lithium carbamate (1.5–4 g) can increase renal glutamate excretion in patients with bipolar disorder. The effect of lithium may be due to reduced renal tubular reabsorption.

---

In primary cultured rat brain pericytes, exposure to 1 mM or 5 mM glutaric acid for 24 hours did not affect cell viability as measured by sulforhodamine B assay. No changes in cell morphology, actin filament arrangement, or PDGFRβ expression were observed after 24 hours exposure to 5 mM glutaric acid. [3]
In acute rat brain cortical slices, propidium iodide incorporation showed no significant difference in pericyte death between glutaric acid-treated slices and controls, indicating that vessel constriction was not due to cell death. [3]

[1]. Yang SY, et, al. Production of glutaric acid from 5-aminovaleric acid by robust whole-cell immobilized with polyvinyl alcohol and polyethylene glycol. Enzyme Microb Technol. 2019 Sep;128:72-78.
[2]. Boy N, et, al. Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis. 2017 Jan;40(1):75-101.
[3]. Isasi E, et, al. Glutaric Acid Affects Pericyte Contractility and Migration: Possible Implications for GA-I Pathogenesis. Mol Neurobiol. 2019 Nov;56(11):7694-7707.

Glutaric acid is a colorless crystal or white solid. (NTP, 1992)
Glutaric acid is an α,ω-dicarboxylic acid, belonging to the linear five-carbon dicarboxylic acids. It is a metabolite in both humans and the large flea (Daphnia magna). It is an α,ω-dicarboxylic acid and a dicarboxylic acid fatty acid. It is the conjugate acid of glutaric acid (1-) and glutaric acid.
Glutaric acid is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain).
Glutaric acid has also been reported in soybean (Glycine max), fruit fly (Drosophila melanogaster), and other organisms with relevant data.
Glutaric acid is a simple five-carbon linear dicarboxylic acid. Glutaric aciduria is characterized by the accumulation of glutaric acid in the body, ranging from mild or intermittent elevation of urinary glutaric acid to severe organic aciduria. Glutamic aciduria type I is an autosomal recessive genetic disorder caused by a deficiency of mitochondrial glutaryl-CoA dehydrogenase (EC 1.3.99.7, GCDH), an enzyme involved in the metabolism of lysine, hydroxylysine, and tryptophan. Glutamic aciduria type I leads to nonspecific developmental delay, hypotonia, and macrocephaly, often accompanied by prenatal brain atrophy. Treatment primarily involves restricting lysine intake, carnitine supplementation, and intensive therapy during concurrent illness. The main principle of dietary therapy is to reduce the production of glutaric acid and 3-hydroxyglutaric acid by restricting protein intake, especially lysine (A3441, A3442).
See also: Carboxylic acids, C6-18 and C5-15-dicarboxylic acids (notes moved to); Carboxylic acids, dicarboxylic acids, C4-6 (notes moved to).
Therapeutic uses

Experimental uses: Glutamic acid has in vitro antiviral activity against a variety of viruses, such as rhinovirus and herpesvirus.
Drugs (Veterinary Drugs): Glutaric acid and para-aminobenzoic acid can block net fluid secretion caused by cholera toxin or heat-stable enterotoxin of Escherichia coli. The tissue examined was the ligated jejunal loop of weaned piglets.
Drugs for Animal Diabetes and Biochemical Research

---

Glutaric aciduria type I (GA-I) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine (C5DC). Diagnosis is confirmed by elevated concentrations of these metabolites in urine, plasma, or dried blood spots, and by GCDH gene mutation analysis or enzyme activity measurement. Newborn screening using tandem mass spectrometry to detect C5DC can identify affected individuals. Untreated, most infants develop acute encephalopathic crises with striatal injury and movement disorders. Treatment includes a low-lysine diet, carnitine supplementation, and emergency management during catabolic episodes. [2]
In GA-I patients, macrocephaly is a frequent but nonspecific finding. Subdural hemorrhage may occur and can be mistaken for abusive head trauma. Bitemporal fluid collections and frontotemporal hypoplasia are characteristic neuroradiologic findings. [2]
In vivo proton magnetic resonance spectroscopy has detected increased intracerebral concentrations of glutaric acid and 3-hydroxyglutaric acid in GA-I patients, particularly in high excreters. [2]
Mechanistically, glutaric acid has been shown to induce capillary constriction in brain slices, likely via indirect effects on pericytes mediated by other cells of the neurovascular unit, as it did not directly contract isolated pericytes in culture. Glutaric acid-treated astrocytes release soluble factors that inhibit pericyte migration without affecting proliferation, suggesting a role in vascular dysfunction and impaired angiogenesis in GA-I. [3]

C5H8O4

132.1146

132.042

110-94-1

Glutaric acid-d6;154184-99-3;Glutaric acid-d4;19136-99-3;Glutaric acid-d2;43087-19-0

743

LARGE, MONOCLINIC PRISMS
COLORLESS CRYSTALS

1.3±0.1 g/cm3

302.9±15.0 °C at 760 mmHg

95-98 °C(lit.)

151.2±16.9 °C

0.0±1.4 mmHg at 25°C

1.477

-1.04

2

4

4

9

104

0

O([H])C(C([H])([H])C([H])([H])C([H])([H])C(=O)O[H])=O

JFCQEDHGNNZCLN-UHFFFAOYSA-N

InChI=1S/C5H8O4/c6-4(7)2-1-3-5(8)9/h1-3H2,(H,6,7)(H,8,9)

pentanedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~946.11 mM)
H2O : ≥ 100 mg/mL (~756.89 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (15.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (15.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (15.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)