Tags

Type your tag names separated by a space and hit enter

Heme-Cu bound aβ peptides: spectroscopic characterization, reactivity, and relevance to Alzheimer's disease.
J Am Chem Soc. 2011 Oct 05; 133(39):15545-52.JA

Abstract

Recently, it has been shown that heme binds to Aβ peptides which may play a major role in Alzheimer's disease (AD). This study illustrates that Aβ peptides can bind both Cu and heme cofactors at the same time. Both cofactors have unique spectroscopic and electrochemical features which are unaffected in the presence of the other, implying that they are electronically, chemically, and electrochemically uncoupled. These data clearly indicate that Cu cannot bind to three histidine residues simultaneously in Cu-Aβ complexes as previously proposed, since one of the histidines is involved in binding heme. The heme-Aβ and the heme-Cu-Aβ peptide complexes function as peroxidases. Interestingly, the Cu-Aβ complex also exhibits peroxidase activity, which may have significant implications in AD. Both Cu(+)-Aβ and heme (Fe(2+))-Aβ complexes reduce O(2) to H(2)O(2) quantitatively. Only one of the two electrons that are required for the reduction of O(2) to H(2)O(2) is derived from the reduced metal site, while the Tyr(10) residue of the native Aβ peptide donates the second electron. This Tyr(10) residue, the source of electron for the generation of partially reduced oxygen species (PROS, e.g., H(2)O(2)) is absent in rodents, which do not get affected by AD. When both heme and Cu are bound to the Aβ peptides, which is likely to happen physiologically, the amount of toxic PROS generated is maximum, implying that heme-Cu-Aβ complexes could potentially be most toxic for AD.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Pramanik D
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India 700032.
Ghosh C
No affiliation info available
Dey SG
No affiliation info available

MeSH

AbsorptionAlzheimer DiseaseAmino Acid SequenceAmyloid beta-PeptidesCatalytic DomainCoenzymesCopperHemeHumansModels, MolecularMolecular Sequence DataPeptide FragmentsPeroxidasesReactive Oxygen SpeciesSpectrum Analysis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21870836

Citation

Pramanik, Debajyoti, et al. "Heme-Cu Bound Aβ Peptides: Spectroscopic Characterization, Reactivity, and Relevance to Alzheimer's Disease." Journal of the American Chemical Society, vol. 133, no. 39, 2011, pp. 15545-52.
Pramanik D, Ghosh C, Dey SG. Heme-Cu bound aβ peptides: spectroscopic characterization, reactivity, and relevance to Alzheimer's disease. J Am Chem Soc. 2011;133(39):15545-52.
Pramanik, D., Ghosh, C., & Dey, S. G. (2011). Heme-Cu bound aβ peptides: spectroscopic characterization, reactivity, and relevance to Alzheimer's disease. Journal of the American Chemical Society, 133(39), 15545-52. https://doi.org/10.1021/ja204628b
Pramanik D, Ghosh C, Dey SG. Heme-Cu Bound Aβ Peptides: Spectroscopic Characterization, Reactivity, and Relevance to Alzheimer's Disease. J Am Chem Soc. 2011 Oct 5;133(39):15545-52. PubMed PMID: 21870836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heme-Cu bound aβ peptides: spectroscopic characterization, reactivity, and relevance to Alzheimer's disease. AU - Pramanik,Debajyoti, AU - Ghosh,Chandradeep, AU - Dey,Somdatta Ghosh, Y1 - 2011/09/13/ PY - 2011/8/30/entrez PY - 2011/8/30/pubmed PY - 2012/1/27/medline SP - 15545 EP - 52 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 133 IS - 39 N2 - Recently, it has been shown that heme binds to Aβ peptides which may play a major role in Alzheimer's disease (AD). This study illustrates that Aβ peptides can bind both Cu and heme cofactors at the same time. Both cofactors have unique spectroscopic and electrochemical features which are unaffected in the presence of the other, implying that they are electronically, chemically, and electrochemically uncoupled. These data clearly indicate that Cu cannot bind to three histidine residues simultaneously in Cu-Aβ complexes as previously proposed, since one of the histidines is involved in binding heme. The heme-Aβ and the heme-Cu-Aβ peptide complexes function as peroxidases. Interestingly, the Cu-Aβ complex also exhibits peroxidase activity, which may have significant implications in AD. Both Cu(+)-Aβ and heme (Fe(2+))-Aβ complexes reduce O(2) to H(2)O(2) quantitatively. Only one of the two electrons that are required for the reduction of O(2) to H(2)O(2) is derived from the reduced metal site, while the Tyr(10) residue of the native Aβ peptide donates the second electron. This Tyr(10) residue, the source of electron for the generation of partially reduced oxygen species (PROS, e.g., H(2)O(2)) is absent in rodents, which do not get affected by AD. When both heme and Cu are bound to the Aβ peptides, which is likely to happen physiologically, the amount of toxic PROS generated is maximum, implying that heme-Cu-Aβ complexes could potentially be most toxic for AD. SN - 1520-5126 UR - https://www.unboundmedicine.com/medline/citation/21870836/Heme_Cu_bound_aβ_peptides:_spectroscopic_characterization_reactivity_and_relevance_to_Alzheimer's_disease_ L2 - https://doi.org/10.1021/ja204628b DB - PRIME DP - Unbound Medicine ER -