The effect of in vitro homocystinuria on the suckling rat hippocampal acetylcholinesterase.

Abstract

UNLABELLED:

Homocystinuria is due to enzymatic deficiencies resulting in elevated blood levels of homocysteine (Hcy), homocystine (Hci), and/or methionine (Met) and the clinical presentation of mental retardation, seizures, and cardiovascular disease. Since these symptoms may be closely implicated with acetylcholinesterase (AChE) activity, we aimed to investigate whether this metabolic disorder affects the hippocampal AChE activity in 21 days suckling Wistar rat hippocampus. Various concentrations of Hcy, Hci (0.05-0.5 mM), or Met (0.05-2 mM) as well as Mixture A (Mix A) (0.3 mM (Hcy)+0.2 mM (Hci)+1.0 mM (Met) = in vitro cystathionine beta-synthase deficiency homocystinuria), Mix B1 (Hcy 0.3 mM + Hci 0.2 mM=in vitro severe methylenetetrahydrofolate reductase deficiency homocystinuria) or Mix B2 (Hcy 0.1 mM+Hci 0.05 mM=in vitro mild methylenetetrahydrofolate reductase deficiency homocystinuria) were preincubated with homogenized hippocampii or with eel Electrophorus electricus pure AChE. AChE was evaluated spectrophotometrically. Hcy or Met stimulated hippocampal AChE by 50% (p < 0.001) at low concentrations of the amino acids (up to 0.3-0.5 mM), whereas Hci inhibited the enzyme by 40% (p < 0.001). Mix A, Mix B1, or Mix B2 activated hippocampal AChE by 40, 30, (p < 0.001), and 12% (p < 0.01), respectively. In contrast, the S-containing amino acids, Mix A, Mix B1, Mix B2 failed to affect the pure AChE activity.

CONCLUSIONS:

a) The presence of -SH group in Hcy and Met may result in hippocampal AChE stimulation and the redox isomer Hci in the inhibition of the enzyme, probably by producing free radicals, and b) The SH-amino acids seem to affect the hippocampal enzyme indirectly, possibly by lipid(s)-protein modifications(s) and Hci by inducing oxidative stress, since no effect was observed on pure AChE activity.

• Authors: Kleopatra H Schulpis, Konstantinos Kalimeris, Constantinos Bakogiannis, Theodore Tsakiris, Stylianos Tsakiris
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 21 Issue 1 Pg. 21-8 (Mar 2006) ISSN: 0885-7490 [Print] United States
• PMID: 16773467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids, Sulfur
• Homocysteine
• Homocystine
• Methionine
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Amino Acids, Sulfur (metabolism)
• Animals
• Animals, Suckling
• Electrophorus
• Enzyme Activation (drug effects)
• Hippocampus (enzymology)
• Homocysteine (pharmacology)
• Homocystine (pharmacology)
• Homocystinuria (metabolism)
• In Vitro Techniques
• Methionine (pharmacology)
• Oxidation-Reduction
• Oxidative Stress (physiology)
• Rats
• Rats, Wistar