A pinch of poison is good for a body, at least if it is heme, and researchers, including one of Indian-origin, have now found how the body turns this toxin into a nutrient know for its role at the core of hemoglobin...
A pinch of poison is good for a body, at least if it is heme, and researchers, including one of Indian-origin, have now found how the body turns this toxin into a nutrient know for its role at the core of hemoglobin, the component of red blood cells responsible for transporting oxygen.
In minuscule amounts, heme works in cells as an essential catalyst called a cofactor and as a signaling molecule to trigger other processes.
“Poor heme management can cause things like Alzheimer’s, heart disease, and some types of cancers, so cells have to do a good job of managing how much heme is available,” said Amit Reddi, Assistant Professor at Georgia Institute of Technology in the US.
The labile heme serves as a nutrient instead of a poison. But to make sure things stay that way, heme needs to be carefully trafficked through the cell, Reddi said.
“By having biosensors that can monitor heme in cells, we have this new window into how cells make this essential toxin available in carefully sparse concentrations,” he said.
The researchers used ratiometric sensor to illuminate heme’s movements.
People may recognise heme from its role at the core of hemoglobin, the component of red blood cells responsible for transporting oxygen.
The ionic iron in the heme molecule is what the oxygen molecule sticks to.
In hemoglobin, the heme is embedded tightly in protein, rendering it non-toxic.
For the research, published in the journal Proceedings of the National Academy of Sciences. the team designed a fluorescent sensor molecule to keep tabs on how hem is carefully trafficked through the cell
With heme at very low baseline levels, the sensor lit up bright green and as heme concentration increased, it caused the light to fade out.
Using the heme sensors, the researchers found an enzyme, GAPDH, known for its involvement in breaking down sugar, got tied up in proteins, leaving only a limited amount free for biochemical reactions.
When more labile heme is needed, nitric oxide, a signaling molecule, rapidly released heme from entangling proteins, so it could do jobs such as regulating gene expression.
“Ratiometric fluorescent techniques have been around for a while, but our technique is new, because it specifically senses heme,” Reddi said.
“We took a heme binding protein from bacteria and clipped it onto to green fluorescent protein,” he explained.