R Narayanasami studies the neuronal nitric oxide synthase (nNOS) enzyme, which plays a critical role in the brain by producing nitric oxide, a molecule that helps neurons communicate. A key part of their research examines how chaotropic reagents—substances that can disrupt the structure of proteins—can temporarily increase the enzyme's activity. By exposing nNOS to these chemicals, they discovered a dramatic increase in the enzyme's capability to transfer electrons, shedding light on how the enzyme's shape influences its function. Understanding these mechanisms could lead to new therapeutic approaches for neurological conditions where nitric oxide plays a role.
Key findings
Chaotropic reagents, like urea and guanidine hydrochloride, can increase the activity of neuronal nitric oxide synthase by 20-fold.
The structural changes induced by chaotropic agents reveal hidden aspects of the enzyme that enhance its electron transfer capabilities.
The study highlights the relationship between enzyme structure and function, opening avenues for the development of drugs that mimic the natural activation of this enzyme.
Frequently asked questions
Does Dr. Narayanasami study brain enzymes?
Yes, Dr. Narayanasami focuses on neuronal nitric oxide synthase, an important enzyme in the brain.
What treatments has Dr. Narayanasami researched?
While not directly focused on treatments, their research could inform drug development that targets enzyme regulation in the brain.
Is Dr. Narayanasami's work relevant to neurological conditions?
Yes, understanding nitric oxide synthesis is crucial for developing therapies for various neurological disorders.
Publications in plain English
The stimulatory effects of Hofmeister ions on the activities of neuronal nitric-oxide synthase. Apparent substrate inhibition by l-arginine is overcome in the presence of protein-destabilizing agents.
1999
The Journal of biological chemistry
Nishimura JS, Narayanasami R, Miller RT, Roman LJ, Panda S +1 more
Plain English This study looked at how certain ions (called Hofmeister ions) influence the activity of a brain enzyme that produces nitric oxide (NO), a key molecule in signaling within the nervous system. Researchers found that the presence of sodium perchlorate (NaClO4) helped boost the production of NO, particularly when other compounds that interfere with this process were also present. This is significant because understanding how to enhance NO production could lead to new treatments for conditions related to nerve function.
Who this helps: This benefits patients with neurological disorders and their doctors by providing insights into potential therapies.
Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate biotransformation by diphenyleneiodonium sulfate.
1998
Biochemical pharmacology
McGuire JJ, Anderson DJ, McDonald BJ, Narayanasami R, Bennett BM
Plain English This study looked at how a chemical called diphenyleneiodonium sulfate (DPI) affects the breakdown of glyceryl trinitrate (GTN), a drug used for heart conditions. The researchers found that DPI significantly inhibited the enzyme important for activating GTN, reducing its effect by over 90% when combined with NADPH. This matters because it reveals a new way that GTN works in the body and highlights the role of a specific enzyme in heart drug metabolism.
Who this helps: This benefits patients with heart conditions who rely on medications like GTN for effective treatment.
Relationships between NADPH diaphorase staining and neuronal, endothelial, and inducible nitric oxide synthase and cytochrome P450 reductase immunoreactivities in guinea-pig tissues.
1997
Histochemistry and cell biology
Young HM, O'Brien AJ, Furness JB, Ciampoli D, Hardwick JP +4 more
Plain English This study looked at the relationship between a specific staining method, called NADPH diaphorase staining, and four enzymes (types of nitric oxide synthase and cytochrome P450 reductase) in guinea pig tissues. The researchers found that in some tissues, like the brain and blood vessels, NADPH diaphorase staining generally matched the presence of these enzymes, but in other tissues, the staining did not align with any of the enzymes studied. This is important because it shows that while NADPH diaphorase staining can indicate certain enzyme activities, it is not a reliable way to identify all related enzymes in different tissues.
Who this helps: This helps researchers and doctors better understand enzyme activity in various tissues, which could improve strategies for disease treatment.
The influence of chaotropic reagents on neuronal nitric oxide synthase and its flavoprotein module. Urea and guanidine hydrochloride stimulate NADPH-cytochrome c reductase activity of both proteins.
1997
Nitric oxide : biology and chemistry
Narayanasami R, Nishimura JS, McMillan K, Roman LJ, Shea TM +3 more
Plain English Researchers exposed a brain enzyme called neuronal nitric oxide synthase to chemicals that unfold proteins, and found that these chemicals temporarily boosted the enzyme's ability to transfer electrons by 20-fold—an effect similar to what happens when a natural cellular activator called calmodulin turns the enzyme on.
The boost occurred because the unfolding chemicals exposed hidden parts of the enzyme's structure that enhanced electron movement, though the enzyme's activity eventually returned to normal within an hour.
This matters because it reveals how the shape of this enzyme controls its function, which could help scientists understand how the brain naturally regulates this enzyme and potentially develop new drugs that mimic its activation.
Flavin-binding and protein structural integrity studies on NADPH-cytochrome P450 reductase are consistent with the presence of distinct domains.
1995
Archives of biochemistry and biophysics
Narayanasami R, Horowitz PM, Masters BS
Plain English This study looked at a specific enzyme called NADPH-cytochrome P450 reductase, which is important for transferring electrons in the body. Researchers found that when they used urea to alter the environment, the enzyme changed its structure and lost its flavin components in a way that could be reversed with lower concentrations of urea. At a concentration of 3 M urea, the researchers observed a maximum change in the protein’s structure and flavins dissociating, helping to clarify how the enzyme works.
Who this helps: This research helps scientists and medical professionals better understand how certain drugs are metabolized in the body.
31P NMR spectroscopic studies on purified, native and cloned, expressed forms of NADPH-cytochrome P450 reductase.
1992
Biochemistry
Narayanasami R, Otvos JD, Kasper CB, Shen A, Rajagopalan J +4 more
Plain English This study looked at different forms of an enzyme called NADPH-cytochrome P450 reductase, which is important for various biochemical processes. Researchers used a special technique called 31P NMR spectroscopy to explore how this enzyme interacts with certain molecules (flavins) and to analyze lipids extracted from tissues. They found that certain mutations in the enzyme affected its activity and how it binds to flavins; specifically, one mutation resulted in only 20% of normal activity, while another mutation completely stopped the enzyme's function.
Who this helps: This helps researchers and scientists working on drug metabolism and enzyme function.