Anaerobic heme recycling by gut microbes: Important methods for monitoring porphyrin production.

Heme is the most abundant species of iron inside the human body and an essential cofactor for numerous electron/chemical group transfer reactions and catalyses, especially those involving O. Whole anaerobic biomes exist that also depend on heme but lack widespread, O-dependent pathways for heme synthesis and breakdown. The gastrointestinal tract is an anaerobic ecosystem where many microbes are auxotrophic for heme, and where the abundant members of the Bacteroidetes phylum convert heme into iron and porphyrins.

Intermediates involved in the reduction of SO: insight into the mechanism of sulfite reductases.

Sulfite reductases (SiRs) catalyze the reduction of SO to HS in biosynthetic sulfur assimilation and dissimilation of sulfate. The mechanism of the 6e/6H reduction of SO at the siroheme cofactor is debated, and proposed intermediates involved in this 6e reduction are yet to be spectroscopically characterized. The reaction of SO with a ferrous iron porphyrin is investigated, and two intermediates are trapped and characterized: an initial Fe(III)-SO species, which undergoes proton-assisted S-O bond cleavage to form an Fe(III)-SO species.

Homologous acetone carboxylases select Fe(II) or Mn(II) as the catalytic cofactor.

Acetone carboxylases (ACs) catalyze the metal- and ATP-dependent conversion of acetone and bicarbonate to form acetoacetate. Interestingly, two homologous ACs that have been biochemically characterized have been reported to have different metal complements, implicating different metal dependencies in catalysis. ACs from proteobacteria and share 68% sequence identity but have been proposed to have different catalytic metals.

Reduction of Sulfur Dioxide to Sulfur Monoxide by Ferrous Porphyrin.

The reduction of SO to fixed forms of sulfur can address the growing concerns regarding its detrimental effect on health and the environment as well as enable its valorization into valuable chemicals. The naturally occurring heme enzyme sulfite reductase (SiR) is known to reduce SO to H S and is an integral part of the global sulfur cycle. However, its action has not yet been mimicked in artificial systems outside of the protein matrix even after several decades of structural elucidation of the enzyme.

Spin state dependent peroxidase activity of heme bound amyloid β peptides relevant to Alzheimer's disease.

The colocalization of heme rich deposits in the senile plaque of Aβ in the cerebral cortex of the Alzheimer's disease (AD) brain along with altered heme homeostasis and heme deficiency symptoms in AD patients has invoked the association of heme in AD pathology. Heme bound Aβ complexes, depending on the concentration of the complex or peptide to heme ratio, exhibit an equilibrium between a high-spin mono-His bound peroxidase-type active site and a low-spin bis-His bound cytochrome b type active site. The high-spin heme-Aβ complex shows higher peroxidase activity than free heme, where compound I is the reactive oxidant.

Second Sphere Interactions in Amyloidogenic Diseases.

Amyloids are protein aggregates bearing a highly ordered cross β structural motif, which may be functional but are mostly pathogenic. Their formation, deposition in tissues and consequent organ dysfunction is the central event in amyloidogenic diseases. Such protein aggregation may be brought about by conformational changes, and much attention has been directed toward factors like metal binding, post-translational modifications, mutations of protein etc.

Simultaneous binding of heme and Cu with amyloid β peptides: active site and reactivities.

Amyloid imbalance and Aβ plaque formation are key histopathological features of Alzheimer's disease (AD). These amyloid plaques observed in post-mortem AD brains have been found to contain increased levels of Cu and deposition of the heme cofactor. The increased Cu concentration and heme co-localization together with other heme related dysfunctions hint towards the likely association of the metal and cofactor in the pathology of the disease.

Intermediates involved in serotonin oxidation catalyzed by Cu bound Aβ peptides.

The degradation of neurotransmitters is a hallmark feature of Alzheimer's disease (AD). Copper bound Aβ peptides, invoked to be involved in the pathology of AD, are found to catalyze the oxidation of serotonin (5-HT) by HO. A combination of EPR and resonance Raman spectroscopy reveals the formation of a Cu(ii)-OOH species and a dimeric, EPR silent, CuO bis-μ-oxo species under the reaction conditions.

Peroxidase activity of heme bound amyloid β peptides associated with Alzheimer's disease.

The amyloid cascade hypothesis attributes the neurodegeneration observed in Alzheimer's disease (AD) to the deposition of the amyloid β (Aβ) peptide into plaques and fibrils in the AD brain. The metal ion hypothesis which implicates several metal ions, viz. Zn, Cu and Fe, in the AD pathology on account of their abnormal accumulation in the Aβ plaques along with an overall dyshomeostasis of these metals in the AD brain was proposed a while back.

Formation of compound I in heme bound Aβ-peptides relevant to Alzheimer's disease.

Proteolysis of Amyloid Precursor Protein, APP, results in the formation of amyloid β (Aβ) peptides, which have been associated with Alzheimer's disease (AD). Recently the failure of therapeutic agents that prohibit Aβ aggregation and sequester Cu/Zn in providing symptomatic relief to AD patients has questioned the amyloid and metal ion hypothesis. Alternatively, abnormal heme homeostasis and reduced levels of neurotransmitters in the brain are hallmark features of AD.

Nitrite reductase activity of heme and copper bound Aβ peptides.

A significant abundance of copper (Cu) and iron in amyloid β (Aβ) plaques, and several heme related metabolic disorders are directly correlated with Alzheimer's disease (AD), and these together with co-localization of Aβ plaques with heme rich deposits in the brains of AD sufferers indicates a possible association of the said metals with the disease. Recently, the Aβ peptides have been found to bind heme and Cu individually as well as simultaneously. Another significant finding relevant to this is the lower levels of nitrite and nitrate found in the brains of patients suffering from AD.