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Activation of intestinal mitochondrial phospholipase D by polyamines and monoamines
M Madesh1, K A Balasubramanian
1Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore, India.
Abstract:
Intestinal mitochondria have a phospholipase D (PLD) activity which was stimulated by polyamines and monoamines resulting in the formation of phosphatidic acid (PA) from endogenous phospholipids. When stimulated by polyamines, mitochondrial PLD utilized endogenous phosphatidylethanolamine (PE) as substrate whereas stimulated by monoamines, both PE and phosphatidylcholine (PC) were hydrolysed. Stimulation of PA formation by spermine was enhanced by the presence of calcium. Since polyamines are known to alter the calcium transport by mitochondria and PA is known to possess an ionophore effect, stimulation of PA formation in mitochondria by polyamines suggests that polyamine-induced alteration in calcium homeostasis might involve a PA related mechanism.
Insights
Intestinal mitochondria possess phospholipase D activity, producing phosphatidic acid (PA) when stimulated by amines. This suggests a potential role for PA in how polyamines affect mitochondrial calcium levels.
Area of Science:
- Mitochondrial biochemistry
- Cellular signaling
Background:
- Intestinal mitochondria exhibit phospholipase D (PLD) activity.
- This activity is modulated by amines, leading to phosphatidic acid (PA) generation.
Purpose of the Study:
- To investigate the role of intestinal mitochondrial phospholipase D (PLD) activity.
- To determine the substrates and modulators of PLD in intestinal mitochondria.
- To explore the potential link between polyamine-induced calcium alterations and PA formation.
Main Methods:
- Enzymatic assays to measure PLD activity in isolated intestinal mitochondria.
- Substrate specificity analysis using endogenous phospholipids like phosphatidylethanolamine (PE) and phosphatidylcholine (PC).
- Investigation of the effects of polyamines (e.g., spermine) and monoamines on PLD activity and PA formation, including the role of calcium.
Main Results:
- Mitochondrial PLD activity was stimulated by both polyamines and monoamines, producing PA from endogenous phospholipids.
- Polyamines primarily utilized PE as a substrate, while monoamines hydrolyzed both PE and PC.
- Spermine-induced PA formation was enhanced by calcium, suggesting a calcium-dependent mechanism.
Conclusions:
- Intestinal mitochondrial PLD activity is modulated by amines, generating PA.
- Polyamines, particularly spermine, stimulate PA formation in a calcium-dependent manner.
- PA formation may be a key mechanism in polyamine-induced alterations of mitochondrial calcium homeostasis.