Tryptophan! You have heard of it, that wonder amino acid that supposedly causes acute narcolepsy in those who partake in too much Thanksgiving dinner, rendering entire families somnolescent. It turns out that it really doesn’t do that after all. The reason everyone nods off is because you stuffed yourself full with rich foods and the football game is boring.
But there’s more to tryptophan than just late November urban legends. You can make all kinds of things with tryptophan, both in the course of protein synthesis and as a precursor to other molecules that have differing biological purposes. Serotonin is an example of the latter, being one chemical step away from the structure of tryptophan, with the brief addition of tryptophan hydrolase, the enzyme that assists in this structural conversion. Serotonin is the neurotransmitter that not only assist in the regulation of the central nervous system, but also works to push along your colon’s muscle movements. Yes, without tryptophan, you couldn’t build the signalling chemicals that make you crap.
Tryptophan isn’t something you can synthesize internally, however, it is an essential amino acid that must be obtained from food. Plants synthesize it all day long and we can also get it from meats as well, because cows ate grass and we can then pirate the pilfered aminos that way. Almost everything you eat outside of a Twinkie bar will contain some tryptophan, so no worries about getting any for yourself.
One of the more interesting things that contains tryptophan as part of its structure are a class of dimer molecules (a pair of monomers that are structurally similar) called kinesin. For the most part in cellular activity, materials diffuse naturally throughout a cell. When mitochondria generate ATP, it is dispersed throughout the cell where anyone who needs some can pick it up, burn it, and drop the ADP so it can be recharged with a phosphate and turned into ATP again. But sometimes larger cell parts need to be dragged into place, as they don’t float around fast enough to get where they are needed. Proteins such as kinesin (there’s a whole family of them) drag cargo along small polymer microtubes found throughout the cell, sort of like a highway network. Kinesins travel in one direction, away from the nucleus. Microtubules are charged at both ends, and kinesins move toward the positively charged end, which is along the cell wall. (Another class of cellular motors, dynesins, do the exact opposite…they walk their way toward the cell nucleus along the microtubule.)
These kinesins walk their way along the tubule, burning ATP as they go. (As the ATP is burned by hydrolysis, the resulting ADP is released, and fresh ATP is bound at the receptor) They come apart when they reach their destination, the amino acids scattered about to be recycled elsewhere with the help of enzymes at both ends of that process.
So imagine the cell nucleus as the brain controlling all the cellular functions in a generic eukaryotic cell. Soon, the cell will under mitosis and split into two identical cells, but there is much to be done. The chromosomes need to be lined up a certain way, lipids need to be assembed here and there, the cell wall needs to be adjusted, organelles assigned to their station, and of course, cellular respiration needs to be maintained at the same time. Orders are issued from the nucleus in the form of mRNA to assemble proteins and enzymes to signal the formation of even more proteins and enzymes. One task: this lipid must be moved from the nucleus to near the cell wall.
mRNA matches their complement from the central DNA strand along the KIF6 gene. Two proteins are expressed from that RNA that are entwined with the help of enzymes previously constructed. The newly minted kinesin latches onto the microtube, the cargo attached to the top of the protein and walks it along the tube until it reaches the destination, another class of proteins that are handing off fatty acids outside the cell. The cargo is unloaded, the kinesin is disassembled, and not incidentally, generating a bit of heat during the lifespan of the protein, which warms the cell slightly.
Now to haul this cargo, the amino acids at the tip of this complex molecule need to be the right sort. For the KIF6 kinesin, tryptophan makes up a part of that structure. One of the properties of tryptohan is that one end of it is made up of aromatic indole, and is thus hydrophobic. No doubt this special property is helpful in dragging around its cargo in some fashion, but I’m not sure if that has been proven yet.
Now as I said before. the KIF6 gene is the one that controls for the assembly of the entire kinesin, and this gene is basically a sequence of nucleotides that identify the amino acid sequence in groups of three. So if you were to read the sequence (and I’m simplifying a bit here, because DNA has four nucleotides but only three are needed to identify one amino acid) and say, the first three codons are UGG, that means "in this protein sequence, stick a tryptophan here" and then the next sequence is read, that amino acid is added, and so on until the end of the mRNA is reached, the protein is folded and off it goes to work. This process happens all the time, cells are not some static body that occasionally emits a hormone…to even build a hormone requires a lot of this protein building and DNA to RNA transcription all the time just for the cell to get anything done, much less transfer the finished product out of the cell and into the bloodstream where it can do some good.
Genes are not static, they get unspun and recombined all the time and shuffled back together through the wonderous miracle of sexual reproduction. Variations in genes add to the dynamic mix of the gene pool and can add or remove minor traits the the resulting offspring. It is possible to have a gene that does the same thing but code differently through mutation, the resulting different alelles are called polymorphisms, and hence are heritable traits. Common polymorphisms are the color patterns in feline coats…my cat has a polymorphism for the C coloration gene, which gives her the colorpoint scheme because she has two recessive alelles. A cat with one dominant or two dominant C genes doesn’t have a colorpoint coat and will exhibit regular coloration. Incidentally,my cat also has the dominant A (tabby fur pattern) gene but since the coloration isn’t expressed due to the recessive c genes, it doesn’t show up very well. Give he a dominant C and you would probably have a grey and black striped mackeral tabby cat, but she didn’t end up with the polymorphisms needed for proper coloration.
Polymorphisms are expressed throughout the population and are spread via sexual reproduction. While each gene has a specific function, the various polymorphisms of those genes may encode a slightly different protein structure, or cause other proteins to be expressed at different times, and so on. One particular polymorphism that interests me is one for the the KIF6 gene, and involves our friend tryptophan.
Earlier I noted that the codon sequence of tryptophan is UGG. There is a polymorphism of the KIF6 gene that doesn’t have UGG in that particular part of the squence, its a bit error that codes for AGG instead, which is an amino called arginine. The gene polymorphisms are called KIF6/Trp and KIF6/Arg respectively. Bonus: this isn’t a rare polymorphism. Quite a few people have it, although the actual statistics aren’t known precisely, and since you have two copies of this KIF6 gene, you can have a lot of folk who are just carriers for the KIF6/Arg polymorphism and still express the Trp component. Maybe. We think. We don’t know that part just yet.
The replacement of tryptophan with arginine has some sort of consequence for the expressed kinesin protein that KIF6 codes. Arginine doesn’t have an indole group at the end, rather it has guanine, which is a bunch of nitrogens and hydrogens that renders that end of the molecule collectively positive. This change, somehow, the function of the protein, a
lthough what exactly isn’t quite known yet. Perhaps it has trouble moving the cargo around, or can’t grab onto it some of the time, or any number of things.
Note: this is not to say arginine is some evil molecule is hell bent on death and destruction. Rather, you need it, your body can synthesize some of it, you get the rest from diet, and if you didn’t have any at all, you die. I’m saying that in this case, arginine replacing tryptophan has deleterious effects of some sort.
Statistically, people who have KIF6/Arg polymorphisms are at a greater risk of heart disease. Why, again, nobody knows. But the statistical analysis has been done (this is two years ago) and the data is solid. Interestingly enough, the intake of particular statins decreases the risk of coronary disease by a significant amount for carriers of this gene…folks who have just KIF6/Trp don’t get as much benefit from a statin as those with the Trp polymorphism.
Tests are available, now, for this particular gene to see if you are at risk. In fact, I took one, and I’m a carrier for KIF6/Arg (I AM A MUTANT AHAHAHAHHAHAHA) so statins are something I will take from now on to eliminate that risk.