The human body is as fascinating as it is complex to study. Examining what makes us, well us, takes us to the very molecular level of what we are. The makeup of the body goes something like this: the body is comprised of organ systems, organs are comprised of tissues, tissues are made up of cells, and cells communicate, signal and survive with the help of a bunch of other “little stuff” in the body. This “little stuff” consists of compounds like proteins and the amino acids that make them up which keep our bodies in homeostasis (a stable, “happy,” equilibrium state).
What always boggles me is that there are only twenty amino acids and each one can play an extremely different role in the body depending on how they are aligned to make proteins, or even what functional groups they have. This is the second of three blog posts in which I continue to explore the history and science of two specific amino acids—aspartate and glutamate—and what we currently know about their wider functional roles in the body.
Let’s do a quick amino acid review. All amino acids have the same basic structure: a central alpha-carbon, which can attach to four other elements or compounds; an alpha amino group (NH3+); a carboxylic acid group (COO-); and, a “R-group” (some combination of different compounds) which distinguishes each amino acid from the others.
Something that makes glutamate and aspartate special: they are the only two amino acids that are acidic in a human body (this means they have an overall negative charge). They also have very similar R-groups: aspartate has a methylene (CH2) attached to a carboxylic acid (COO-), and glutamate has two methylene (CH2CH2) attached to a carboxylic acid (COO-). Pretty similar, right? That’s what I thought, too. In fact, when I first learned about these amino acids, I did little to distinguish them beyond the number of methlyenes. Yet, as discussed in my first post (link), little molecular differences can have enormous impacts on how the body perceives and uses compounds, and not just in the realm of taste. Here is my basic visual rendering of what’s going on:
But wait, if glutamate and aspartate are structurally so similar, couldn’t the body just rearrange a methylene and get glutamate from aspartate and vise versa? Well, not exactly, although that would be pretty cool. But in theory, this process actually happens. In a study study examining the citric acid cycle (a process in the body that eventually helps create ATP energy) in guinea-pig cerebral-cortex slices, scientists discovered that aspartate could be converted into glutamate via a modified citric acid cycle. How? An enzyme (another category of “little stuff” that helps catalyze, or bring about, various chemical reactions) called aspartate aminotransferase (AST) can help transfer an amino group (NH2) to another molecule (alpha-ketoglutarate), which in turn makes glutamate. (See drawing below and Role of aminotransferases in glutamate metabolism of human erythrocytes).
But wait, if the body can just make this transformation, why do we need both amino acids?
Well, even though these amino acids are so similar and even though we have the mechanisms to convert them between each other, they play a lot of different roles.
In my first post, I discussed how aspartate and glutamate were the amino acids associated with sweet and savory taste, respectively. Considering the major difference between sweet and savory tastes can help us better understand how different these little compounds actually are. Glutamate, for example, plays perhaps the biggest transmitter role in normal brain functioning. This amino acid is the primary fast excitatory synaptic neurotransmitter in the brain. This means a couple of things. First, glutamate is a neurotransmitter (a signaling mechanism that helps move nerve signals between each other). Second, glutamate is used by the majority of excitatory neurons (these help to increase the likelihood of producing an action potential, which is required to move nerve signals and do things such as muscle movements) in the central nervous system.
In plain English, glutamate is required to get information quickly from one place to the other. So would more glutamate present near the brain be good? Just the opposite actually. Glutamate, while extremely important in neurotransmission, has excitotoxic characteristics (the ability to destroy neurons by extending the excitatory state). Studies have shown that too much glutamate can lead to Alzheimer’s disease, Huntington disease, and Parkinson’s disease. (See Glutamate). A recent study has even connected glutamate to Schizophrenia. With all these risks, why would we still want glutamate? Glutamate, as stated above, is the transmitter for brain function. It plays an extremely important role in cognition, memory and learning. So thinking about this blog right now, glutamate is helping your neurons fire so you don’t forget what you’ve read. This most important neurotransmitter is centrally involved in both healthy brain/body function and disease states.
So where does aspartate come in? Besides the (essential!, at least in my opinion) function of conferring sweet–and, much more weakly than glutamate, savory–taste, aspartate plays certain roles that no other amino acids can. For example, like glutamate, aspartate plays a central role in cognition and memory. The N-methyl-D-aspartate (NMDA) receptor, which is made of aspartate and other compounds stuck together, is used in conjunction with glutamate to increase excitatory synapses and thus memory and cognition. NMDA is used to open different ions channels and increase the synapses. Here we see how aspartate, and not glutamate is required to form heterodimer (structures that consisted of several different compounds) receptors for certain processes to take place. (See Is Aspartate an Excitatory Neurotransmitter?). However, like glutamate, excessive aspartate near the external brain can cause excitotoxicity, and damage neurons.
So wait, are you telling me that if I keep eating MSG (containing glutamate) or the artificial sweetener aspartame (containing aspartate), I’ll experience excitotoxicity and my brain cells will all die?
Well, not really. A ton of research has gone into establishing a basic consensus among scientists that excitotoxicity does not just happen because you consume foods with these amino acids; there are, thankfully, a lot of other mechanisms playing roles to try to maintain homeostasis, like the Blood Brain Barrier (BBB). In plain English, the BBB is a form of protection between the brain and the rest of the body; so only certain “little stuff” can get through the capillaries (little vein-like structures that carry blood to the brain), but neither glutamate or aspartate is one of them. Therefore, these amino acids would have to be converted into other compounds or cross the barrier by correct receptors on the BBB. (See Monosodium glutamate neurotoxicity, hyperosmolarity, and blood-brain barrier dysfunction)
So maybe glutamate and aspartate aren’t that different after all? Perhaps structurally and near the brain. But as I explored in my first post, these two little compounds that have similarly different functions in foundational bodily processes also help to create what we understand culturally as completely different tastes: sweetness and savoriness. And thanks to both aspartate and glutamate, I can remember how tasty each one is.
References to check out:
Ellinger, J. J., Lewis, I. A., & Markley, J. L. (2011). Role of aminotransferases in glutamate metabolism of human erythrocytes. Journal of biomolecular NMR, 49(3-4), 221-229.
Herring, B. E., Silm, K., Edwards, R. H., & Nicoll, R. A. (2015). Is aspartate an excitatory neurotransmitter?. Journal of Neuroscience, 35(28), 10168-10171.
McCall, A., Glaeser, B. S., Millington, W., & Wurtman, R. J. (1979). Monosodium glutamate neurotoxicity, hyperosmolarity, and blood-brain barrier dysfunction. Neurobehavioral toxicology, 1(4), 279-283.
Purves, D., Augustine, G. J., Fitzpatrick, D., Katz, L. C., LaMantia, A. S., McNamara, J. O., & Williams, S. M. (2008). Glutamate receptors. Augustine GJFD, Hall WC, LaMantia A, McNamara JO, et al. Neuroscience. Massachusetts, USA: Publishers Sunderland, 126-133.
Simon, G., Drori, J. B., & Cohen, M. M. (1967). Mechanism of conversion of aspartate into glutamate in cerebral-cortex slices. Biochemical Journal, 102(1), 153.