3-methylglutaconic acid

The reduction of acrylic acid was attempted at elevated temperatures. Surprisingly, the reaction was found to yield not only propionic acid, but also the dimer, a-methylglutaric acid. When the reaction was conducted in the absence of hydrogen, the product obtained was 3-methylglutaconic acid, which apparently is the precursor of the saturated dimer formed in a hydrogen atmosphere. Similarly, methacrylic acid yielded a-methylene-y,y-dimethylglutaric acid when heated with cyanocobaltate (II) in the absence of hydrogen. Its structure was established via ozonolysis. Similar dimerizations have been reported for acrylic acid (I, 14), methacrylate ester (7, 11), crotonic acid (13), and its diethylamide (15). 

Methylglutaconic acid (peak II) 273 198 3-Hydroxy adipic lactone 157 201... 

Individuals who are deficient in HMG-CoA lyase are unable to complete the metabolism of leucine. The increased urinary excretion of 3-hydroxy-3-methylglutaric acids is the primary biochemical criterion that distinguishes this particular enzymatic defect from other defects in enzymes of leucine catabolism that also result in metabolic acidosis and abnormal organic aciduria. There is also substantial urinary excretion of intermediates of leucine catabolism, such as 3-methylglutaconic acid, and their metabolites, including 3-hydroxy-isovaleric acid produced from isovaleric acid. 

Hydroxyisovaleric add 3-Methylglutaconic acid 3-Methylglutaric acid C5-Hydroxyacylcarnitine C -Unsaturated acylcarnitine... 

At no time were ketone bodies detected in her urine, and there was no evidence of any abnormal excretion of amino acids. However, a number of abnormal organic acids were detected in her urine, including relatively large amounts of 3-hydroxy-3-methylglutaric and 3-hydroxy-3-methylglutaconic acids. The excretion of these two acids increased considerably under two conditions ... 

I 3-Hydroxy-3-methylglutaric acid Z2 3-Methylglutaconic acid O 3-Methylglutaric acid 3-Hydroxyisovaleric acid... 

They are defects in the degradation pathways of leucine, isoleucine, and valine. These conditions are usually diagnosed by examining organic acids in urine with abnormal metabolites also notable on acylcamitine profile. Organic acidemias comprise a variety of disorders and include methylmalonic acidemia (MMA), propionic acidemia (PROP), isovaleric acidemia (IVA), glutaric acidemia type 1 (GA-1), 3-methylcrotonyl carboxylase deficiency (3-MCC), 3-methylglutaconic acidemia (3-MGA), and vitamin B12 uptake, transport, and synthesis defects. 

Glutaconic acid derivatives have been used extensively for the synthesis of 2,6-pyridinediols however, there has been relatively little interest in these compounds during the past ten years. /S-(p-Methoxypheriyl)glutaconic acid (Xn-6) and methylamine orbenzylaminegiveN-methyl-or/V-benzyl 6 hydroxy 4-(p-methoxyphenyI)-2-pyridone (Xn-7). )3-Methylglutaconic anhydride and... 

The base-catalyzed condensation reaction of the C15 aldehyde (4) with methyl P-methylglutaconate (536) gave the retinoic acid derivative (537), which is substituted in the tetraene side chain by an additional carboxyl group. 

Urinary excretion of specific organic acids may suggest a mitochondrial defect. Cytochrome c oxidase defects and other respiratory chain defects have been demonstrated in some patients with ethylmalonic aciduria or 3-methylglutaconic aciduria. In certain cases intermediates of the citric acid cycle are also found in increased amounts in the urine. 

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