Adam and Eve? Or Alanine and Serine?

What if the defining reason for life on Earth is the manipulation of time? While organic matter has been discovered in outer space, in the form of methane in the ethers of Neptune and Uranus, and asteroids and meteorites that crashed into Earth (Organic Compounds in the Solar System, 2016), why have we not yet discovered extraterrestrial life in the form of a cell that is moving, eating, growing, changing, and replicating (Sagan & Sagan, 2018)?

The defining feature of life could be the enzyme: proteins made from amino acids that increase the rate of chemical reactions. Metabolic reactions could not occur without enzymes (Lewis & Stone, 2020), as reactions would occur too slowly to interact with one another. Enzymes increase the speed of reactions so that complex, multifaceted interactions can occur to create and sustain life. It is the enzyme that has catalyzed life on Earth, by shortening the time needed for reactions to take place.

Although amino acids have been discovered in some meteorites, such as the simpler alanine and glycine found in class CI and CN meteorites (Organic Compounds in the Solar System, 2016), the 20 main ones that define life on Earth have not yet been found elsewhere in the universe in same concentrations and varieties.

There is much debate surrounding the origin of the 20 amino acids. Is it by chance or by evolutionary design? And are more amino acids evolving or could they evolve? Other amino acids do exist, including selenocysteine which is found in humans, but is comparatively more complex to utilize, which might be a clue as to why there aren’t more than the 20 main ones that exist (Brazil, 2017).

Francis Crick hypothesized in his frozen accident theory that 20 specific amino acids exist by chance and that any other number of structures could have been used to synthesize proteins (Koonin, 2017). However, in 2017 Doig makes strong arguments that the 20 main amino acids with their specific hydrophobicity enable folding, stability, accessibility of active sites, and metabolic efficiency, making amino acids the perfect building blocks for proteins and enzymes (Doig, 2017).

Why are C, H, N, O, and S the organic molecules that compose amino acids? In addition to being bountiful on our planet, these elements are ideal for many reasons. In contrast, metals such as selenium and antimony are too soluble in water and therefore unstable. Halogens are too electronegative and reactive. Silicon bonds too readily to oxygen in place of other elements. The list goes on and on to account for the specificity that explains why our current amino acids are the perfect constituents of life (Doig, 2017).

So, if it is not a frozen accident then why has the number of amino acids stopped at approximately 20 when so much of evolution is characterized by seemingly endless diversity? One fascinating theory explains it in terms of simple logistics. tRNA (transfer RNA) reads the genetic code from RNA, and then using the enzyme aminoacyl tRNA synthetase, selects which amino acid tRNA should bind to. tRNA then transfers the selected amino acid to a ribosome for assembly on the growing polypeptide chain. tRNA has only 3 reading sites, and after accounting for the start and stop codons, 61 possible amino acids reading codes. However, tRNAs are limited in their recognition ability (Saint-Léger et al., 2016). tRNAs already make on average one mistake for every 1000-10,000 codon readings and adding more amino acids would enable more mistakes. Dr. Ribas explains it this way, “It’s like if you have a very simple kind of lock where you could only change three or four pins, you come to a point where you wouldn’t be able to make new keys because a new key will open a lock you have already used and that defeats the purpose” (Brazil, 2017).

Photo Credit: (National Human Genome Research Institute, 2019)

Scientists do not have all the answers on whether amino acids evolved by chance or limited necessity, but one thing is certain; the 20 amino acids are brilliant in their specificity and enable life as we know it. Without proteins, we would not have enzymes, and without enzymes, we would still be a pool of RNA and co-factors. Enzymes alter the speed of reactions and amino acids are the specific building blocks of all proteins and enzymes. Without our 20 amino acids, we would lack the complex web of reactions needed to create life; organisms that can move, eat, breathe and reproduce.

 

REFERENCES

Organic Compounds in The Solar System. (2016, May 26). Chemistry LibreTexts. https://chem.libretexts.org/Ancillary_Materials/Exemplars_and_Case_Studies/Exemplars/Physics_and_Astronomy/Organic_Compounds_in_The_Solar_SystemLinks to an external site.

Sagan, D., & Sagan, C. (2018). life | Definition. In Encyclopædia Britannica. Retrieved from https://www.britannica.com/science/lifeLinks to an external site.

Lewis, T., & Stone, W. L. (2020). Biochemistry, Proteins Enzymes. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554481/#:~:text=Enzymes%20are%20proteins%20comprised%20ofLinks to an external site.

Brazil, R. (2017). Why are there 20 amino acids? Chemistry World. https://www.chemistryworld.com/features/why-are-there-20-amino-acids/3009378.articleLinks to an external site.

Doig, A. J. (2017). Frozen, but no accident – why the 20 standard amino acids were selected. The FEBS Journal, 284(9), 1296–1305. https://doi.org/10.1111/febs.13982 Links to an external site. 

Koonin, E. (2017). Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code. Life, 7(2), 22. https://doi.org/10.3390/life7020022 Links to an external site. 

Saint-Léger, A., Bello, C., Dans, P. D., Torres, A. G., Novoa, E. M., Camacho, N., Orozco, M., Kondrashov, F. A., & Ribas de Pouplana, L. (2016). Saturation of recognition elements blocks evolution of new tRNA identities. Science Advances, 2(4). https://doi.org/10.1126/sciadv.1501860Links to an external site.

National Human Genome Research Institute. (2019). Transfer RNA (tRNA). Genome.gov. https://www.genome.gov/genetics-glossary/Transfer-RNA

The Inner Life of a Cell

For a myriad of reasons, I am now on a path toward medical school. I will share some of my writings here, in case anyone is interested in biochemistry or other musings! This is a post I created for a biochemistry discussion board, as part of a class I am taking at the University of California San Diego, extended online.

This is a response to this incredible 8 minute video created by Harvard Online, “The Inner Life of the Cell”

"The Inner Life of the Cell" illustrates one of the main reasons people fall in love with the field of biology. This video is overwhelmingly inspiring in how it demonstrates, with a striking visual aesthetic, the vast intricacies of microbiological processes. I watched it several times in slow motion with closed captioning, as it is incredibly dense and yet only scratches the surface of complex processes within cells.

This video reminded me of a profound concept from one of our first lectures. The biochemist Jacques Monod expressed the idea of the unity of biochemistry when he said, "Anything found to be true of [the bacterium] E. coli must also be true of elephants" (Tymoczko et al., 2019). In other words, structure, function, and processes occurring on microbiological levels have related similarities to structure, function, and processes on larger scales. This demonstrates commonalities in life on various levels, giving further evidence that life evolved from chemicals into molecules, into the complex multi-celled organisms that currently inhabit our planet.

From reading other reactions in this discussion board, I see I am not the only one fascinated by the motor proteins that have feet-like ‘heads’ that ‘walk’ along microtubules. Our fascination is perhaps rooted in this founding concept of unity in biochemistry, as what is perhaps so awe-inspiring about motor proteins is that their movements mirror human walking. But are we anthropomorphizing molecules?

This train of thought led me to delve deeper into the concept of unity in biochemistry. I discovered numerous additional biochemists who extrapolated Monod's claim:

"The unity of biochemistry . . . surely represents one of the most profound insights into the nature of life." (Harold 2001, 58)

"And the result was the enunciation of the most far-reaching generalization. . . . The basic similarity in the biochemical behavior of so many different organisms is now generally admitted. . . . The recognition of this unity is Kluyver's great contribution." (van Niel 1949, 168-69)

However, this concept of unity is challenged in a fascinating 2004 essay by Herbert C. Friedmann in John Hopkins University Press. Friedmann claims that the unity of chemistry is an attractive idea for multiple reasons but has caused bias in research practices. Many studies are centered on the hypothesis of proving similarities. Are we missing out on important research findings because we're stuck in this too-neat paradigm?

The biochemist Efraim Racker poses a provocative question:

"The concept of "unity in biochemistry" has for more than half a century oriented scientific thinking and experimentation in comparative biochemistry. The conspicuous lack of success of a rational approach to chemotherapy has served as a key witness for the "unitarians." However, the steadily growing recognition of the existence of alternate pathways, of qualitative and quantitative differences in enzymatic patterns, of differences in submicroscopic cell structure, permeability and rate of cell division have been quoted in favor of a "disunity in biochemistry." The assessment of those features that are not common to various cells might serve to provide us with a better understanding of the disease process as well as its control." (Racker 1954, vii)

Being aware of the limitations of this concept may enable scientists to make even more discoveries moving forward. As one can see from this video, the inner life of the cell is profoundly complex, and maintaining an objective mind can be challenging, given our human tendency to anthropomorphize and categorize.

My interest in the origins of this concept came from my fascination with motor proteins. I would like to end with a little information about these ‘walking molecules’ .

There are about 45 different types of motor proteins in the human body (Sweeney and Holzbaur, 2022). Functions of motor proteins include separating chromosomes during mitosis and meiosis, and enabling the movement of cilia and flagella. Muscle fiber contraction is made possible by myosin motor proteins, and cytoplasmic dynein and kinesins are in charge of the active transport of proteins and vesicles inside cells (Motor Protein. Wikipedia, 2022).

The video Protein Packing Inside the Cell (BioVisions) depicts in exquisite detail how kinesins moved toward negatively charged axon terminals while carrying synaptic vesicles containing neurotransmitters. I discovered that ATP fuels each movement. Binding is made possible by electrostatic steering and conformational changes. (I had to look up electrostatic steering and found out it's a binding process managed by the manipulation of charges that allows an attraction between two substances (Electrostatic Steering at Acetylcholine Binding Sites. 2019). In other words, kinesin-controlled positive and negative attraction causes the feet to bind and unbind to the microtubule. Given the density of proteins inside cells, kinesin has a limited ability to diffuse, so if it fully detaches from the microtubule it frequently re-attaches. What causes a kinesin to "know" when to start moving? As soon as it bonds with a vesicle, its stalk opens up.

Motor proteins are fascinating molecules that either further Monod’s concept of the unity of chemistry or are merely coincidental in their similarities and inspire the human tendency to anthropomorphize. In any case, the microbiological research that is being done will only serve to further reveal the microscopic mechanisms that enable life.

 

REFERENCES

Tymoczko, John L., et al. Biochemistry: A Short Course. 2019, p. 122.

Franklin M. Harold. The Way of the Cell : Molecules, Organisms, and the Order of Life. Oxford University Press, 2001. EBSCOhost, https://search-ebscohost-Mocom.ezproxy.lib.ryerson.ca/login.aspx?direct=true&db=nlebk&AN=129270&site=ehost-liveLinks to an external site.

Van Niel, C. B. "the "Delft School" and the Rise of General Microbiology." Bacteriological Reviews, vol. 13, no. 3, 1949, pp. 161-174. https://pubmed.ncbi.nlm.nih.gov/16350131/ Links to an external site. 

Friedmann, Herbert C. "From Butyribacterium to E. Coli : An Essay on Unity in Biochemistry." Perspectives in Biology and Medicine, vol. 47, no. 1, 2004, pp. 47-66. https://pubmed.ncbi.nlm.nih.gov/15061168/ Links to an external site. 

Racker, Efraim, 1913. Cellular Metabolism and Infections; Symposium Held at the New York Academy of Medicine, March 4 and 5, 1954. Academic Press, 1954, New York (State), 1954, p. 57. https://doi.org/10.1002/jps.3030440522 Links to an external site. 

Sweeney, H. Lee, and Erika L. F. Holzbaur. "Motor Proteins." PubMed Central (PMC), www.ncbi.nlm.nih.gov/pmc/articles/PMC5932582 Links to an external site.  Accessed 10 Nov. 2022.

"Motor Protein - Wikipedia." Motor Protein - Wikipedia, en.wikipedia.org/wiki/Motor_protein Accessed 10 Nov. 2022.

"Protein Packing Inside the Cell (BioVisions) (Official Version)." YouTube, 16 Mar. 2020,www.youtube.com/watch?v=Jr5KEpBj_KQLinks to an external site. 

"Electrostatic Steering at Acetylcholine Binding Sites." Electrostatic Steering at Acetylcholine Binding Sites - ScienceDirect, 6 Jan. 2009, www.sciencedirect.com/science/article/pii/S0006349506718410 Links to an external site.