Umami Science Part IV: Inside the Venus Flytrap

And now we come to umami science at its most fundamental: the chemical process that plays out in our taste cells when we eat savory foods and experience umami.  

Umami, we've learned, is caused by the glutamate present in abundance in ramen's ingredients, and amplified by nucleotides through the phenomenon known as "umami synergy."  But how exactly do these molecules make us perceive umami?  In the final installment of Ramen Chemistry's series on umami science, we're going to answer that question by visiting the surface of a taste cell, where a venus flytrap (of a molecular sort) lurks on the surface.  This venus flytrap has an appetite for just one thing--glutamate, preferably with a side of nucleotide--and when it bites down on a meal, it sets off a cascade of cellular signals that causes the brain to say "delicious!"  

Venus Flytraps.  Well, not this kind of venus flytrap.  Conservatory of Flowers, GG Park.  Photo: Ramen Chemistry.  

Background: Sensory Perception and Cellular Communication

We learned in Part II how the "basic tastes" all derive from the interactions of particular dietary molecules--i.e., glutamate (umami), sugars (sweetness), acids (sourness),  sodium chloride (saltiness)--with chemical receptors on the surface of taste cells.  There is a special receptor for each basic taste--one for sweetness, one for umami, and so on.  It's important to understand that when I use the term "receptor" here, what I mean is a protein; a protein that sits on a taste cell and makes physical contact with a taste molecule like glutamate or sugar.   

Taste Signaling. Those things marked "T1R2, T1R3" are the venus flytrap receptor proteins that recognize sweet chemicals, setting off a chain of chemical events inside the taste cell, ultimately causing the brain to perceive sweetness.  Umami works the same way.  Image www.qiagen.com (full link here).

This interaction between the taste molecule and its protein receptor is the first step in the perception of taste.  It starts what scientists call a signal transduction pathway.  Signal transduction is how we perceive and respond to external stimuli, and how our cells communicate with each other to get anything done in our bodies.

Now, don't let your eyes glaze over at the sight of a term like signal transduction!  It's easy to understand.  It works like this: a stimulus--a taste or smell molecule, light, a hormone, a neurotransmitter, etc.--starts the process by interacting with a receptor protein on a cell surface.  The receptor protein responds to the stimulus by changing its shape and, in effect, turning "on." That shape change ripples through the cell surface, causing something to happen inside the cell. What follows is a cascade of events in which a succession of proteins is turned on, each causing the next event in the molecular sequence.  The end result is a precise physiological response--the taste of umami, the scent of jasmine, or the perception of the color blue.      

Umami and the Venus Flytrap

We just learned that the first step in any taste process occurs when a taste molecule causes a taste receptor protein to change its shape.  In the umami receptor, that shape change happens in a part of the protein called a "venus flytrap domain" (VFT).  The VFT is made of two lobes connected by a sort of atomic hinge.  Those lobes can be open or they can snap shut, which is why its called a venus flytrap.  Under normal circumstances, the VFT prefers to be open. It's more stable that way.

Tangential Relationship.  Ramen from Ramen Kyouka, Hiroko's ramen school teacher's restaurant in Tokyo (left). Venus flytrap (right). 

Things change when glutamate comes along.  That's because right near the VFT's hinge is a tiny pocket that is specially adapted to fit a glutamate molecule.  When glutamate enters this pocket, its atoms interact with the atoms in both lobes, causing the two lobes to close around it.   Glutamate acts as a molecular glue, increasing the stability of the closed VFT.  This is hugely important, because the closed form of the VFT is the active form: an umami taste signal is sent to the brain only when the VFT is closed.  

Umami Signal Cascade. When the VFT closes around glutamate, it causes a shape distortion in another part of the umami receptor, triggering a series of molecular events resulting in umami taste.

It turns out that this opening and closing of the VFT also explains umami synergy.  Inside the VFT there are actually two pockets.  One for glutamate and another, further from the hinge, for the nucleotides IMP and GMP.  Umami synergy occurs when glutamate is in its pocket, and IMP or GMP is simultaneously in the adjacent nucleotide pocket.  The nucleotide, in essence, increases the strength of the glue, making the closed VFT even more stable.  The more stable the closed VFT becomes, the more umami signal is sent to the brain.  

Synergy Happens in the Flytrap. Glutamate (yellow) up against the VFT's hinge.  IMP (green) sits next door, at the mouth of the flytrap. The contacting amino acids in the VFT surround.  This 2008 paper in the Proceedings of the National Academy of Sciences, entitled "Molecular mechanism for the umami taste synergism" showed the molecular basis for umami synergy: http://www.pnas.org/content/105/52/20930.full

And with that, we've finished umami science.  I have tried to write this series for scientists and non-scientists alike, and it's my hope that all readers have learned something new.  Up next, Ramen Chemistry will get back to the business of starting a restaurant.  Stay tuned.  

Umami Science Part III - Umami Synergy

Have you ever thought about why we dip sushi in soy sauce?  We know it makes the fish taste a lot more delicious, but why?  Today we'll learn that when we combine the glutamate in soy sauce with the nucleotides in fish, we amplify the umami taste sensation well beyond what either ingredient alone produces.  This fascinating phenomenon is called umami synergy.

Umami synergy involves the relationship between umami-causing glutamate (MSG) and two additional molecules, the nucleotides inosinate (IMP) and guanylate (GMP).  IMP and GMP do not cause umami on their own.  But when present alongside glutamate, they are capable of amplifying the umami taste fifteen-fold.  Not only is the umami taste magnified, it is more sustained and longer lasting, too.  This phenomenon, only recently unraveled at the molecular level, plays a role in worldwide cuisine, driving us to combine ingredients rich in glutamate with those rich in IMP and GMP.  

Umami Synergy. Please stop by the soy sauce on the way into my mouth. Thx. REUTERS/Issei Kato

Maximizing Umami Taste: Umami Synergy

Umami synergy is a sort of culinary gestalt: the whole is far greater than the sum of the parts. Glutamate produces umami.  Nucleotides (GMP and IMP) by themselves produce no umami. Together, they produce an umami sensation that dwarfs the sensation caused by just glutamate.  

This phenomenon has a significant influence on the foods we eat.  One source explains that "major world cuisines have traditionally relied on umami synergy for deliciousness by combining protein foods with IMP and vegetables with glutamate."  We've learned how umami synergy drives the flavor of Japanese dashi broths, by combining the glutamate of kombu with the IMP of bonito flakes or the GMP of dried shiitakes.  But Western cuisine is full of examples, too.  Tomato sauce (glutamate) combined with meat (inosinate) in pasta Bolognese; cheeses (glutamate) and beef (inosinate) in French onion soup or cheeseburgers; and cheese plus anchovies (inosinate) in Caesar salad.  The point is that humans implicitly understood umami synergy, using it to their culinary advantage, well before "umami" was discovered in the early 1900s.  

Now let's talk about the umami compounds and why they're in our foods.  Then we'll learn how the ways we prepare our food increase the concentration these molecules, maximizing our umami taste experience.   

Umami Synergy.  This is a new way to think about beef stew. Umami Information Center.

The Umami Compounds

The fact that our foods are often rich in glutamate, inosinate, and guanylate isn't surprising. Present in every living thing, these molecules are absolutely central to biology on our planet.

As we learned in Part II, Professor Kikunae Ikeda discovered umami in 1908 when he extracted purified glutamate from kombu.  Just a few years later, one of Ikeda's students, Shintaro Kodama, succeeded in identifying IMP as an umami compound when conducting studies on katsuobushi (dried bonito flakes).  It wasn't until 1960 that another Japanese scientist, Akira Kuninaka, uncovered GMP's umami-enhancing properties when he isolated it from shiitake mushroom broth. Kuninaka also discovered the umami synergy phenomenon.

Glutamate, as we've learned, is an amino acid.  Amino acids are the building blocks of proteins. Proteins, in turn, are large amino acid polymers, characterized by complex three-dimensional structures and sophisticated biological functions.     

Amino Acids and Proteins. Structures of the 20 naturally occurring amino acids, called as such because they possess an "amine" (NH2) group and a carboxylic acid (COOH) group. Glutamate at lower right (left). Proteins are chains of amino acids that fold themselves into highly complex three-dimensional structures (right).  

All of the amazing complexity and diversity of proteins derives from just 20 amino acid building blocks in mammals.  Of those 20, the human body can synthesize only 10.  We have to get the other 10--the "essential" amino acids--from our food.  And unlike fats and starches, our bodies don't store excess amino acids; we need to consume them on a daily basis to keep all our internal trains moving on time.  Amino acids have a range of important biological functions beyond just populating proteins.  For example, our entire umami discussion here is premised on free glutamate's role in triggering a complex cellular signaling pathway en route to the taste of umami.  

Recipe for "chicken stock with umami synergy" at http://umami2u.blogspot.com/2012/12/chicken-stock-with-umami-synergy.html.

IMP and GMP, in contrast, are nucleotides.  Nucleotides are the building blocks of the nucleotide polymers, DNA and RNA.  Three things make a nucleotide a nucleotide is (1) a 5-carbon sugar, connected to (2) a phosphate group, and (3) a nitrogen-containing ringed structure called either a purine or a pyrimidine.  Inosinate is the common precursor to two of the five nucleotides used in DNA and RNA, adenylate and guanylate (the other umami nucleotide).  Free nucleotides--like ATP, the fundamental currency of energy in living things--are just as important in biology as their polymeric counterparts.  IMP is high in meats and fish because muscle cells in animals need a lot of ATP to function.  One source explains that "[o]lder animals with very well exercised muscles tend to have more umami, as do fish that are heavy swimmers, such as mackerel, salmon, and tuna."  In fact, it's well-known that older stewing hens make better chicken stock than young birds do (see here, here, and here).

Nucleotides. Phosphate connected to sugar connected to base. Nucleotides are responsible for umami synergy. http://www.uic.edu/classes/bios/bios100/lectures/dna.htm

Maximizing Umami Compounds: The Power of Cooking and Fermentation

Just as important for our food discussion is the fact that these biomolecules--proteins, DNA, RNA, ATP--are broken down after an organism dies, increasing the amounts of glutamate and the umami nucleotides in the food source that the organism becomes.  

The key thing to note is that food preparation has a significant role in maximizing umami.  As one author explains, "[p]rocesses such as cooking, boiling, steaming, simmering, roasting, braising, broiling, smoking, drying, maturing, marinating, salting, ageing and fermenting all contribute to the degrading of the cells and macromolecules of which the foodstuff is made."  Enzyme-mediated breakdown through processes like fermentation is particularly effective in bringing out umami.  

One great example is katsuobushi (dried bonito flakes):  drying the bonito fish can increase the inosinate concentration 30-fold as cellular ATP is broken down!  The same principle applies at sushi restaurants, where the tastiest tuna has likely been aged for a few days before service to a customer, maximizing its umami.   

ATP Breakdown = Umami.  Well, for a while.  ATP content is high in animal muscle, because it is needed to power contraction.  ATP stops being produced after an animal is slaughtered, and immediately begins to degrade.  Inosinate (IMP) is produced within 24 hours, but degrades further in subsequent days.  Increasing amounts of inosine and hypoxanthine indicate decreasing freshness.  http://www.novocib.com/Freshness_Assay_Kits.html.

Next time, we're going into some serious science here at Ramen Chemistry.  We're finally ready to understand how umami happens at the molecular level.  Stay tuned.

Umami Science Part II - Taste Phenomena and the Discovery of Umami

OK, so now we know that umami has a huge role in worldwide cuisine.  It's got a Japanese name, but it's hardly an exclusive Japanese thing.  Nevertheless, given the prevalence of umami in Japanese food, it's not terribly surprising that a Japanese scientist first "discovered" umami as a distinct taste phenomenon with a distinct molecular basis.   And this was only about 100 years ago, meaning that the "umami" concept is a pretty recent one, even in Japan.  

Umami was discovered by Kikunae Ikeda, a chemist at Tokyo Imperial University (today's University of Tokyo, Japan's most elite school).  After a contemporary hypothesized that "good taste stimulates digestion" Ikeda was apparently inspired to research the connection between flavor and nutrition.  Having grown up eating large amounts of kombu dashi (high-umami broth made from a kind of kelp called kombu in Japan), Ikeda had noticed something unique about dashi.  It was mild, yet highly distinctive.  It wasn't sweet, salty, sour, or bitter.  So Ikeda set out to identify the chemical basis of kombu's flavor.

Original MSG. The first Ajinomoto product (left) and Professor Ikeda's lab notebook (right).  Photo Ajinomoto.  

The Basic Tastes

In order to understand the significance of Ikeda's discovery, we need to understand the concept of "basic tastes."  According to Ikeda, "physiologists and psychologists recognize only the four tastes sour, sweet, salty and bitter."  He distinguished other apparent "tastes" as being something else:  "A hot sensation is just a skin mechanical sensation" and "such qualities as metallic, alkaline and astringent are not considered to be tastes (at least not pure tastes), because they cannot be separated from the sensation accompanied by tissue damage."  

Now let's pause for a second and consider that last statement.  How does one draw a line around what constitutes a "taste" and what doesn't?  Ikeda was writing before we knew a whole lot about cell biology, so we'd like to know how these phenomena are classified by modern scientists.  It seems that the five "basic tastes" all are due to interactions of particular chemical compounds with associated chemical receptors in the taste buds.  

Tongue.  Up close with a scanning electron microscope.

As a recent article entitled "The Cell Biology of Taste" explains, taste "is the sensory modality generated when chemicals activate oral taste buds and transmit signals to a different region of the brainstem."  But the article goes on to state that "[t]aste is commonly confused with flavor, the combined sensory experience of olfaction [smell] and gustation [taste]."  It "is also commonly confused with somatosensory sensations such as the cool of menthol or the heat of chili peppers."  This latter phenomenon, through which other non-taste nerves in the mouth "are capable of responding to irritative chemical stimulation" is referred to as "chemesthesis."  Generally speaking, chemesthetic sensations include (1) chemical irritation and pungency (examples include capsaicin in chili peppers, piperine in black pepper, gingerol in ginger); (2) astringency (examples are tannins and ethanol in wine); and (3) cooling (menthol in mints).  

All that said, research on taste is still evolving.  For example, "The Cell Biology of Taste" explains that "evidence is mounting that fat may also be detected by taste buds via dedicated receptors," meaning that "fat" may turn out to be a sixth basic taste (fatty flavor has historically been viewed, like chemesthesis, as  "somatosensory" in that it derives from a food's texture rather than arising through a gustatory signaling pathway).  

The linked articles above, as well as this BBC piece, are really illuminating if you're interested in further reading on taste science and chemesthesis.  

Signaling Pathways.  The basic tastes and their associated cellular protein receptors (left).  The mechanisms by which the five basic tastes operate in taste cells (right).  Excellent and detailed explanations of both figures here: http://jcb.rupress.org/content/190/3/285.full.  

A Bit About Evolutionary Biology

So why do we experience these basic tastes in the first place?  Why did we develop these complex signaling pathways so that we could experience the tastes of sugars, organic acids (sourness), glutamate, and salt?  Professor Ikeda was inspired by the notion that "good taste stimulates digestion." And that notion--that taste sensations send a message to the stomach to prepare for digestion of the kinds of foods being eaten--is tied to the evolutionary history of taste.  

Taste evolved not only as a means of stimulating digestion.  It also evolved as a way to lead us toward nutritious foods--and away from poisonous ones.  One scientist explains it this way:  "Among the five tastes, salty, sweet and umami (meaty or savory) are appetitive, driving us toward essential nutrients, whereas bitter and sour are aversive, alerting us to potentially harmful substances."  And another pair of authors tells us that each of the various basic tastes "is believed to represent different nutritional or physiological requirements or pose potential dietary hazards."  

An Acquired Taste.  Bitter melon.

Sweetness signals the presence of carbohydrates, saltiness signals critical dietary salts, and umami signals protein. Bitterness is described as "innately aversive" and signals the presence of toxic compounds (it's no coincidence that a lot of poisons actually taste bitter).  It's probably not a coincidence that our sensitivity to bitter compounds is significantly stronger than our sensitivity to sweet compounds.   Sourness is considered "generally aversive," because our bodies want to control the amount of organic acids taken in.  That's also why spoiled foods, which contain lots of acids, often have a sour taste.  

Adding Umami to the Basic Taste Roster

Let's go back to Ikeda's seminal 1909 paper, entitled "New Seasonings," in which he postulated that "there is one other additional taste which is quite distinct from the four tastes.  It is the peculiar taste which we feel as 'umai' [loosely translated as "savory" or "delicious"] arising from fish, meat, and so forth. . . . I propose to call this taste 'umami' for convenience."   

Ikeda employed a painstaking series of extractions, chemical separations, and crystallizations to ultimately identify ionic glutamic acid as the source of umami.  And when I say "painstaking," I mean it.  Ikeda worked in an age before the technological revolution gave us the wide array of powerful analytical instruments we now have at our disposal.  The techniques he used are practically a lost art today.  An article in the Journal Chemical Senses distills Ikeda's work as follows:  it "was done with the procedures of classical chemistry, aqueous extraction, removal of large-scale contaminants [] by crystallization, lead precipitation and numerous other steps of preparative chemistry.  Finally, low-pressure evaporation resulted in the slow crystallization of a single substance with the mass formula C5H9NO4: glutamic acid."  

How Times Have Changed.  Ikeda probably worked in a lab like this one at MIT (top).  His task would be a lot easier today with techniques like LC-MS (liquid chromatography-mass spectrometry) (bottom).

Reading "New Seasonings," one is struck by the number and variety of steps Ikeda had to undertake in order to take a piece of kelp and reduce it down to pure crystals of the single molecule responsible for umami (actually he took 38,000 grams--about 84 pounds--of dried kelp, and reduced it to 30 grams of glutamate).  Getting there must have required a tremendous amount of trial, error, and, above all, patience.  

For this achievement, Ikeda has been named one of Japan's "Ten Great Inventors" by the Japanese Patent Office.  But Ikeda took it a step further and commercialized his invention.  As he explained in his paper, "[a] rational method of production satisfying this natural preference [for umami] must be developed."  And so it was.  Ikeda obtained a patent on his process and partnered with "Mr. Saburosuke Suzuki, a well-known iodine vendor," and created Ajinomoto, the company that pioneered the commercialization of MSG.  If you see MSG in a grocery store today, there's a good chance it's sold by Ajinomoto.  

Ikeda and Ajimoto.  http://www.ajinomoto.com/en/aboutus/principles/

You can read more about Professor Ikeda and his discovery here, here, and here, if you want to know more.  

Next time, we'll find out about umami synergy: the way certain ribonucleotides act in concert with glutamate to significantly amplify the umami response.   

Umami Science Part I - How to Think About Umami

So far, we’ve been navigating the basics of ramen here at Ramen Chemistry.  Ramen is our product after all, so that's how I kicked off this blog.  But Ramen Chemistry is not a food blog, per se.  It’s about every aspect of the ramen business.  Once Shiba Ramen secures a physical space (hopefully soon), our lives are going to revolve around getting the business open, and Ramen Chemistry is going to reflect the the diverse things we'll be doing to make it happen.

But here in the last days of (relative) calm before our fire drill starts, I want to take a short detour into the world of science.  Chemical biology and food science, that is.  I want to tell you about the molecular basis for the human umami response.  This is real, current science and it relates to ramen.  Let’s get started!

MSG. Monosodium glutamate. This unnecessarily controversial compound is naturally abundant in many foods we eat every day (see below). 

What Is Umami?

Umami (literally "delicious taste" in Japanese) is, along with sweetness, saltiness, sourness, and bitterness, one of the five basic tastes.  It is often described as having savory or mouth-watering quality.  The umami response is triggered by free L-glutamate (one of the 20 naturally occurring amino acids, the building blocks of proteins), usually in the form of its sodium or potassium salt.  The sodium salt is, of course,  monosodium glutamate, MSG.  And, as we'll discuss, the glutamate-induced umami response is strengthened when either of two ribonucleic acids (the building blocks of RNA), guanylate or inosinate, is present.  Foods that contain these chemicals deliver umami.  That's it.

Umami Foods.  Left image shows amounts of glutamate, inosinate, and guanylate in everyday foods.  Right image shows umami-rich foods worldwide.  These images were taken from this very informative article. 

I remember the first time I read about umami. It was in some magazine (I think on an airplane) about a decade ago.  The article described umami as the “elusive Japanese fifth flavor.”  That phrase “elusive” persisted in my thinking for years, in part perhaps because the article’s phrasing—Japanese fifth flavor—left me with the impression that umami was somehow a uniquely Japanese phenomenon.  If that was true, umami may well be elusive to anyone not steeped in Japanese food and culture.  

Umami is elusive, but not because it’s foreign.  Although it’s perhaps more prevalent in Japanese cuisine, with its heavy use of high-umami ingredients like kombu and dried fish, umami has a long history in Western cooking.  The ancient Romans were wild about garum, a fermented fish paste that was full of umami.  A recent article explains that "like Asian fish sauces, the Roman version was made by layering fish and salt until it ferments.  There are versions made with whole fish, and some just with the blood and guts."  The process "creates a fermentation environment that releases more of the protein, making garum a good source of nutrients" and giving "it a rich, savory umami taste."  A food historian is quoted as saying that garum is "very, very flavorful.  It explodes in the mouth and you have a long, drawn-out flavor experience, which is really quite remarkable."

Garum Amphora.  Floor mosaic from garum shop in Pompeii.  The favored condiment in ancient Rome was an umami-heavy paste made of fermented fish guts.

Today, we're wild about pizza, burgers, bacon, roasted tomatoes, oysters, parmesan cheese.  Have you ever eaten at Umami Burger?  Their concept is to make burgers that are umami-maximized.  They do it by invoking non-traditional burger ingredients (and combinations thereof).  They have umami-maximized ketchup on the table, and a very nice appetizer plate of high-umami pickles.  I've eaten there a couple times, and there's a definite difference in how these burgers taste.  Eating one and thinking about its flavor compared to a normal burger is actually a pretty good way of isolating the umami flavor and getting a better sense of what it is.

Umami Burger.  Parmesan frisco, shiitake mushrooms, roasted tomato, caramelized onions, umami house ketchup.

Umami is elusive because of its relative subtlety.  It doesn’t jump out in the obvious way the other four flavors—sweet, salty, sour, bitter—do.  Think about all of the times you’ve thought something was too sweet or too salty.  You probably never thought that something has too much umami.  Umami is also elusive, I think, because we take umami flavors for granted.  We don’t have the “umami” concept in western culture, and we’re just not used to talking about our food in these terms.  

I like to think of umami this way:  imagine the last time you ate a really good slice of pizza.  You were pretty into it, right?  It was hot, the crust was crispy, and it had so much flavor. You had a hard time stopping after a few pieces.  What flavors did you taste?  There was some sweetness and sourness in the tomato sauce, and maybe something was a little bit salty, but of the flavor in that slice of pizza, how much of it can you really assign to sweetness or saltiness, let alone to sourness or bitterness?  All the pizza’s indefinable savoriness, all that flavor that’s not sweet or salty, sour or bitter—that’s umami.  I'm oversimplifying it a bit, I'm sure, but you get the idea behind this thought experiment.  Next time you have pizza or a bacon cheeseburger, think about this formula and maybe umami will start seeming less elusive:

Umami = Total Flavor – (Sweet + Salty + Sour + Bitter)

Maybe you still can’t totally put your finger on it, but by eliminating sweet, salty, sour, and bitter, you see that something else is hard at work making your pizza taste so good.  That’s umami.  

Next time, I'll explain how umami was discovered and how umami happens down at the molecular level.