NIH shift
Encyclopedia
An NIH shift is a chemical rearrangement where a hydrogen atom on an aromatic ring undergoes an intramolecular
migration primarily during a hydroxylation
reaction. This process is also known as a 1,2-hydride shift. These shifts are often studied and observed by isotopic labeling
. An example of an NIH shift is shown below:
In this example, a hydrogen
atom has been isotopically labeled using deuterium
(shown in red). As the hydroxylase adds a hydroxyl
(the -OH group), the labeled site shifts one position around the aromatic ring relative to the stationary methyl group
(-CH3).
Several hydroxylase enzymes are believed to incorporate an NIH shift in their mechanism, including 4-hydroxyphenylpyruvate dioxygenase
and the tetrahydrobiopterin
dependent hydroxylases. The name NIH shift arises from the U.S. National Institutes of Health
from where studies first reported observing this transformation.
Intramolecular
Intramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule.- Examples :...
migration primarily during a hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
reaction. This process is also known as a 1,2-hydride shift. These shifts are often studied and observed by isotopic labeling
Isotopic labeling
Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...
. An example of an NIH shift is shown below:
In this example, a hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
atom has been isotopically labeled using deuterium
Deuterium
Deuterium, also called heavy hydrogen, is one of two stable isotopes of hydrogen. It has a natural abundance in Earth's oceans of about one atom in of hydrogen . Deuterium accounts for approximately 0.0156% of all naturally occurring hydrogen in Earth's oceans, while the most common isotope ...
(shown in red). As the hydroxylase adds a hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
(the -OH group), the labeled site shifts one position around the aromatic ring relative to the stationary methyl group
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...
(-CH3).
Several hydroxylase enzymes are believed to incorporate an NIH shift in their mechanism, including 4-hydroxyphenylpyruvate dioxygenase
4-Hydroxyphenylpyruvate dioxygenase
4-Hydroxyphenylpyruvate dioxygenase HPPD is an Fe-containing enzyme, that catalyzes the second reaction in the catabolism of tyrosine - the conversion of 4-hydroxyphenylpyruvate to homogentisate.-Function:...
and the tetrahydrobiopterin
Tetrahydrobiopterin
Tetrahydrobiopterin or sapropterin is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin , melatonin, dopamine, norepinephrine ,...
dependent hydroxylases. The name NIH shift arises from the U.S. National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
from where studies first reported observing this transformation.