Glycolysis in energy metabolism during seizures

Abstract

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.

Keywords: 6-diphosphate kinase-1; ATP; ATP receptor; N-methyl-D-aspartate receptor; acid-sensitive 1A ion channel; adenosine receptors; aerobic metabolism; energy metabolism; epilepsy; epileptogenesis; glycolysis; grants-supported paper; intra- and extracellular environment; neural regeneration; neuroregeneration; reviews; termination; voltage-gated Na+ and Ca2+; γ-aminobutyric acid.

Figure 1

Process of glycolysis. Glycolysis is the process by which glucose decomposes into pyruvate in the cytoplasm, accompanied by the generation of a small amount of ATP.

Figure 2

Mechanism of metabolite acidosis and seizure termination. The glycolytic metabolite lactic acid can decrease the pH of tissue via the following ways: (1) inhibiting the activity of glycolytic enzyme 6 diphosphate kinase-1; (2) inhibiting the N-methyl-D-aspartate receptor; (3) activating the acid-sensitive 1A ion channel; (4) strengthening the receptive mechanism of the inhibitory neurotransmitter γ-aminobutyric acid; (5) changing intra- and extracellular environments and (6) other mechanisms such as directly suppressing the activity of voltage-gated Na⁺ and Ca²⁺ channels, and activating adenosine receptors and ATP receptors.

Figure 3

The metabolite lactic acid terminates seizures by inhibiting 6 diphosphate kinase-1(PFK). PKA: protein kinase A.

Figure 4

The metabolite lactic acid terminates seizures by inhibiting N-methyl-D-aspartate (NMDA) receptors.

Figure 5

The metabolite lactic acid terminates seizures by activating acid-sensitive 1A ion channels. ASIC: activation of acid-sensitive 1A.

Figure 6

The metabolite lactic acid terminates seizures by strengthening γ-aminobutyric acid. GAD: Glutanic acid decarboxylase; GABA: γ-aminobutyric acid.