Studies on the Effects of Saturated and Unsaturated Short-Chain Monocarboxylic Acids on the Energy Metabolism of Rat Liver Mitochondria

Gregersen, Niels

doi:10.1203/00006450-197911000-00005

Cited by 34 publications

(26 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The elevated excretion of 3-OH-butyric acid, indicating ketosis, was unexpected in this patients with defective P-oxidation. One possible explanation, however, might be that the accumulated isovaleryl-CoA, indicated by the excretion of isovalerylglycine and 3-OH-isovaleric acid, inhibits the citric acid cycle by inhibiting 2-keto-glutarate oxidation (14), thus channeling acetyl-CoA preferentially towards ketone body production.…”

Section: Discussionmentioning

confidence: 99%

C6—C10-Dicarboxylic Aciduria: Investigations of a Patient with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects

et al. 1982

View full text Add to dashboard Cite

SummaryThe abnormal metabolites-adipic, suberic, and sebacic acidswere detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack.

show abstract

Section: Discussionmentioning

confidence: 99%

C6—C10-Dicarboxylic Aciduria: Investigations of a Patient with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects

et al. 1982

View full text Add to dashboard Cite

show abstract

“…So, the observed reduction of cytochrome oxidase seems to have occurred also secondarily. Gregersen (1979) and Stumpf et al (1980) reported that propionate and other short chain carboxylic acids inhibited oxygen consumption by rat liver mitochondria when a-ketoglutarate, pyruvate or succinate was substrate. In addition, Cathelineau et al (1979) demonstrated that propionate acted to decrease the ATP content of rat liver mitochondria when succinate or glutamate was used as oxidizable substrate .…”

Section: Discussionmentioning

confidence: 99%

Comparison of cytosolic and mitochondrial enzyme alterations in the livers of propionic or methylmalonic acidemia: A reduction of cytochrome oxidase activity.

Hayasaka

Metoki

Satoh

et al. 1982

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

“…It may, therefore, be speculated that the shortand medium-chain monocarboxylic acids, indicated to be accumulated in our patient, contribute to the clinical and biochemical symptoms of the ketotic episodes. Results from a systematic investigation of the effects of short-chain monocarboxylic acids on the energy metabolism of isolated rat liver mitochondria (8) show that isovaleric acid inhibits the oxidation of pyruvate and 2-0x0-glutarate. Hexanoic acid that may be accumulated in the patient before detoxification to adipic acid, also inhibits the fatty acid oxidation (8,12,20).…”

Section: Discussionmentioning

confidence: 99%

“…Results from a systematic investigation of the effects of short-chain monocarboxylic acids on the energy metabolism of isolated rat liver mitochondria (8) show that isovaleric acid inhibits the oxidation of pyruvate and 2-0x0-glutarate. Hexanoic acid that may be accumulated in the patient before detoxification to adipic acid, also inhibits the fatty acid oxidation (8,12,20). If these acids are produced in the mitochondrion, in which they exert their effects, the concentration at the site of action may be toxic, even if the concentration in blood and urine is low.…”

Section: Discussionmentioning

confidence: 99%

Ketotic Episodes in Glutaryl-CoA Dehydrogenase Deficiency (Glutaric Aciduria)

Gregersen

Brandt

1979

Pediatr Res

Self Cite

View full text Add to dashboard Cite

Summawthe ketoacidosis, a pronounced lactic acidosis and lactic aciduria A 7-yr-old boy with glutaryl-CoA dehydrogenase deficiency (glutaric aciduria), presenting periodic episodes of lethargy and ketosis, was studied during two such episodes. The urinary excretions of glutaric and 3-OH-glutaric acids were 3100-7900 and 460-660 &mg creatinine, respectively, during these episodes. Urine samples collected before and after the attacks contained 100-5300 and 230-370 &mg creatinine of glutaric acid and 3-OH-glutaric acids, respectively. During the episodes, glutaconic acid excretion rose from 14-89 to 93-630 pg/mg creatinine. Adipic acid and suberic acid excretions were increased from 17-100 and 2-13 to 74-224 and 16-32 &mg creatinine, respectively. The excretions of conjugates of propionic, isobutyric, 2-Me-butyric, and isovaleric acids, outside and during the attacks, respectively, were: propionic acid, 7-13 and 5-19 &mg creatinine isobutyric acid, 1-7 and 3-15 pg/mg creatinine; 2-Me-butyric acid, 2-9 and 4-34 pg/mg creatinine; isovaleric acid, 0-6 and 3-11 pg/mg creatinine. The excretion of total 2-0x0-acids was increased from 0-12 to 29-75 pg/mg creatinine during the episodes. It is argued that one or more compounds, accumulated as a result of the primary glutarylCoA dehydrogenase deficiency, inhibit the oxidation of the branched-chain amino acids and the fatty acids. During excessive catabolism of amino acids and fatty acids this inhibition results in accumulation of metabolites that are excreted in the urine as conjugates and C6-Clodicarboxylic acids, respectively. Short-and medium-chain monocarboxylic acids are known to affect energy metabolism, and it is, therefore, argued that the short-chain monocarboxylic acids, shown to be accumulated in the patient during the ketotic episodes, may have some pathophysiologic significance. SpeculationKetotic episodes with lethargy and severe hypotonia are another feature of glutaric aciduria due to glutaryl-CoAdehydrogenase deficiency. During such episodes inhibition of the metabolism of branched-chain amino acids and fatty acids, secondary to the inability to metabolize glutaric acid, causes accumulation of branched short-chain monocarboxylic acids and of short-and medium-chain dicarboxylic acids.Straight short-and medium-chain fatty acids influence the mitochondria1 energy metabolism, and it is, therefore, speculated that the short-chain monocarboxylic acids, indicated in the present report to be accumulated in the mitochondria of the patient, contribute to the pathophysiology of the ketotic states.Severe ketoacidotic episodes are a well known feature in a number of the organic acidurias. Patients with propionic, isovaleric, and methylmalonic acidurias are often subject to recurrent crises induced by high protein intake or by infections (13,15,21). The clinical and biochemical presentations of these crises resemble one another closely: vomiting and lethargy followed by neurologic symptoms eventually leading to coma, and often to death. Besides is seen in most cases. The ...

show abstract

Studies on the Effects of Saturated and Unsaturated Short-Chain Monocarboxylic Acids on the Energy Metabolism of Rat Liver Mitochondria

Cited by 34 publications

References 17 publications

C6—C10-Dicarboxylic Aciduria: Investigations of a Patient with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects

C6—C10-Dicarboxylic Aciduria: Investigations of a Patient with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects

Comparison of cytosolic and mitochondrial enzyme alterations in the livers of propionic or methylmalonic acidemia: A reduction of cytochrome oxidase activity.

Ketotic Episodes in Glutaryl-CoA Dehydrogenase Deficiency (Glutaric Aciduria)

Contact Info

Product

Resources

About