Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease
Abstract
:1. Introduction
2. Homocysteine Metabolism
3. Homocysteine Thiolactone
4. N-Homocysteinylated Proteins
5. Hcy-Thiolactone Hydrolyzing Enzymes
5.1. Paraoxonase 1
5.1.1. Consequences of Pon1 Gene Ablation
5.1.2. Pon1 Depletion Downregulates Phf8, Upregulates mTOR Signaling, and Inhibits Autophagy
5.1.3. Pon1 Depletion Upregulates App and Aβ
5.1.4. Pon1 Interacts with App but Phf8 Does Not
5.1.5. Similar Effects of Pon1 Depletion and Hcy-Thiolactone/N-Hcy-Protein on Pathways Leading to Aβ
5.2. Bleomycin Hydrolase
5.2.1. Consequences of Blmh Gene Ablation
5.2.2. Blmh Depletion Downregulates Phf8, Upregulates mTOR Signaling, and Inhibits Autophagy
5.2.3. Blmh Depletion Upregulates App and Aβ and Worsens Cognitive and Neuromotor Deficits
5.2.4. Treatments with Hcy-Thiolactone or N-Hcy-Protein Mimicked the Effects of Blmh Depletion
5.2.5. Blmh Interacts with App, but Phf8 Does Not
5.2.6. Becn1 Interacts with App
5.2.7. Similar Effects of Blmh Depletion and Hcy-Thiolactone/N-Hcy-Protein on Pathways Leading to Aβ
5.3. Biphenyl Hydrolase-like Enzyme
Consequences of Bphl Ablation
6. Conclusions and Future Direction
Funding
Data Availability Statement
Conflicts of Interest
References
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Substrate | PON1 (%) | BLMH (%) | BPHL (%) |
---|---|---|---|
L-Hcy-thiolactone (kcat/Km) | 100 (10 M−1s−1) | 100 (103 M−1s−1) | 100 (7.7 × 104 M−1s−1) |
D-Hcy-thiolactone | 24 | <1 | ND |
γ-Thiobutyrolactone | 545 | <1 | <0.001 |
N-Acetyl-D,L-HTL | <1 | <1 | <0.001 |
L-Hse-lactone | ++++ | − | +++ |
L-Met methyl ester | <1 | ++ | 30 |
L-Cys methyl ester | <1 | ++ | ++ |
L-Lys methyl ester | ND | − | − |
L-Phe ethyl ester | 0 | ND | 16 |
Nε-Hcy-aminocaproate | ND | ++++ | ND |
Val(Nε-Hcy-Lys) | ND | ++++ | ND |
HcyLeuAla | ND | ++++ | ND |
Bleomycin | ND | 500 | ND |
Paraoxon | 330 | − | ND |
Phenyl acetate | 280,000 | − | <0.001 |
Valacyclovir | – | ND | 22 |
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Jakubowski, H. Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease. Int. J. Mol. Sci. 2024, 25, 8095. https://doi.org/10.3390/ijms25158095
Jakubowski H. Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease. International Journal of Molecular Sciences. 2024; 25(15):8095. https://doi.org/10.3390/ijms25158095
Chicago/Turabian StyleJakubowski, Hieronim. 2024. "Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease" International Journal of Molecular Sciences 25, no. 15: 8095. https://doi.org/10.3390/ijms25158095
APA StyleJakubowski, H. (2024). Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease. International Journal of Molecular Sciences, 25(15), 8095. https://doi.org/10.3390/ijms25158095