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Effect of 4-pentenoic acid on intermediate metabolism of Tetrahymena
Abstract:
The growth of Tetrahymena pyriformis strain HSM was strongly inhibited by 4-pentenoic acid. Supplementing the medium acetate reversed the growth inhibition, but pyruvate was ineffective. Glycogen content was much lower in cells grown with 4-pentenoic acid than in controls; this effect was not reversed by acetate or by pyruvate. There was little effect of 4-penteonic acid on the in incorporation of label from [1-14C]acetate, [2-14C]glycerol, [1-14C]ribose, [U-14C]fructose, or [1-14C]glucose into CO2 but incorporation of label into glycogen was inhibited, the strongest inhibition being on acetate and the weakest approximately 20%) on ribose, fructose, and glucose. A 3-compartment model for quantitation of labeled acetyl CoA fluxes was shown to be applicable to Tetrahymena grown in the presence of 4-pentenoic acid, and experiments were performed to establish the flux of [1-14C]acetyl CoA into glycogen, lipids, CO2, glutamate, and alanine. It was evident from the results of these experiments that 4-pentenoic acid did not appreciably inhibit beta-oxidation or lipogenesis, but markedly decreased the glyconeogenic flux of labeled acetyl-CoA from the peroxismal and outer mitochondrial compartments.
Insights
4-pentenoic acid inhibits Tetrahymena pyriformis growth by decreasing glycogen synthesis. Acetate supplementation partially reverses this inhibition, indicating a role in metabolic regulation.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- Tetrahymena pyriformis is a model organism for studying cellular metabolism.
- 4-pentenoic acid is a known inhibitor of fatty acid oxidation.
- Understanding the metabolic effects of 4-pentenoic acid is crucial for cellular studies.
Purpose of the Study:
- To investigate the effects of 4-pentenoic acid on Tetrahymena pyriformis growth and metabolism.
- To determine the specific metabolic pathways affected by 4-pentenoic acid.
- To elucidate the role of acetate and pyruvate in mitigating these effects.
Main Methods:
- Growth inhibition assays of Tetrahymena pyriformis with 4-pentenoic acid.
- Measurement of cellular glycogen content.
- Isotopic labeling studies using [1-14C]acetate and other labeled substrates.
- Application of a 3-compartment model for acetyl-CoA flux analysis.
Main Results:
- 4-pentenoic acid strongly inhibited Tetrahymena pyriformis growth, an effect partially reversed by acetate.
- Glycogen content was significantly reduced in the presence of 4-pentenoic acid.
- 4-pentenoic acid inhibited the incorporation of labeled acetyl-CoA into glycogen but not significantly into CO2, lipids, glutamate, or alanine.
- Glyconeogenic flux of acetyl-CoA was markedly decreased from peroxisomal and outer mitochondrial compartments.
Conclusions:
- 4-pentenoic acid disrupts glycogen synthesis in Tetrahymena pyriformis.
- The compound specifically affects glyconeogenic flux of acetyl-CoA, impacting glycogen formation.
- Acetate plays a role in overcoming the growth inhibition caused by 4-pentenoic acid, likely through metabolic compensation.