February 25, 2002
Homing In On a Receptor for the Fifth Taste
Humans can recognize five tastes: bitter, salty, sour, sweet and
umami. Of the five, however, umami is the most difficult to describe —
it’s the flavor associated with monosodium glutamate (MSG). Now,
researchers have identified a taste receptor that responds to amino
acids, including umami, and they hope to develop a more precise
description of the molecular events that allow the brain to perceive
the five different tastes.
With the discovery of the new receptor, scientists have now
identified taste receptors for amino acids, bitter and sweet tastes.
Given that many amino acids are essential components of our diet, this
work may also aid understanding of how animals, including humans,
regulate nutritional intake to achieve a balanced diet. Better
understanding of taste receptors may permit scientists in the food
industry to formulate new products that have specific tastes.
“Since amino acids are essential building blocks of biologically important molecules, it made evolutionary sense for there to be a taste pathway that would make amino acids attractive to consume.”
Charles S. Zuker
A research team led by Howard Hughes Medical Institute investigator
Charles
S. Zuker at the University of California, San Diego, and Nicholas
J. P. Ryba of the National Institutes of Health reported the
identification of an amino-acid taste receptor in an advanced online
publication in Nature on February 25, 2002.
Zuker’s and Ryba’s groups previously collaborated in
discovering sweet and bitter taste receptors. After they had identified
those receptors, they set their sights on finding a taste receptor for
amino acids, reasoning that one must exist because it had long been
known that humans have the ability to taste umami and other amino
acids. "Since amino acids are essential building blocks of biologically
important molecules such as proteins, it made evolutionary sense for
there to be a taste pathway that would make amino acids attractive to
consume," said Zuker.
In their search for the amino acid receptor, the scientists focused
on T1R receptors, a family of proteins that are distantly related to
receptors in the brain that recognize the amino acid glutamate and
related chemicals. Different T1R genes can be expressed in cells
in different combinations to yields cells that respond to a specific
taste. For example, T1R2 and T1R3, designated T1R2+3,
combine to function as a sweet receptor.
To test various receptor possibilities, the scientists devised a
human cell culture method in which combinations of T1R subunits were
expressed in cells. This permitted the scientists to assess how cells
bearing different combinations of T1R genes responded to
particular amino acids.
Using the cell culture technique, Greg Nelson, a graduate student in
Zuker’s lab, discovered that the combination of cells bearing
T1R1 and T1R3 functioned as a "broadly tuned" receptor that was
stimulated by many amino acids. This "T1R1+3" receptor combination was
highly selective for L-amino acids, which are found in nature. D-amino
acids, which are mirror images of L-amino acids and do not occur
naturally, did not activate the receptor.
The scientist also tested whether their newly identified amino acid
receptor candidate behaved in a manner similar to receptors that
recognize glutamate. A signature of the umami taste is that it is
boosted by purine nucleotides, like IMP. In the cell cultures, IMP
dramatically enhanced the response of T1R1+3 to amino acids.
The researchers next examined the effects of IMP in mice. They added
the chemical to the animals’ taste buds, then added amino acids,
and measured the specific response of nerve fibers connected to the
taste buds that expressed T1R1+3. The response of these nerves was
greatly enhanced by IMP.
In a final set of experiments, Nelson and his colleagues showed that
mice do not taste some artificial sweeteners such as aspartame and
cyclamate that humans can taste because of sequence differences in the
T1R receptors of the two species.
"This last piece of the puzzle is worthy of note," said Zuker.
"Changes in the sequence of taste receptors appear to be responsible
for some of the difference in tasting behavior between mice and
humans."
According to Zuker, discovery of the amino acid taste receptor will
have important implications for understanding the machinery of taste.
"When Nick Ryba and I began this collaboration a bit over four years
ago, our ultimate goal was to understand how the brain knows what you
just tasted," he said. "We wanted to discover how taste receptor cells
are activated and how their signals travel to the brain to produce
specific taste perceptions.
"To do that, we first needed to define the different taste
modalities at a cellular level, so that we could then follow their
connectivity maps to the brain. The ‘Holy Grail’ in this
field has been the receptors, and now that we know the receptors
underlying three modalities – sweet, bitter and amino acid
– we can begin to work on our original goal, to map this system
to understand how taste is encoded," Zuker said.
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