Carbohydrates, commonly referred to as "sugars", are a family of compounds with the general chemical formula of Cn(H2O)n. Among its many roles, carbohydrates serve as a source of carbon and energy for many organisms, including humans. Its appearance in many of life’s most important molecules has led many scientists to believe that carbohydrates, particularly ribose, play a significant role in the origin of life.
Grab some coffee (or the drink of your choice) and let’s take a look at the relationship between carbohydrates and origins of life research. If there is terminology or concept you don't understand, check out the resources included throughout and at the end of the post! References are also included for scholars tracking down primary sources. For the chemists out there, it pains me as well that Wix doesn't support subscript and superscript!
Ribose is a five-carbon carbohydrate that serves as the sugar backbone in ribonucleotides, the monomers that make up RNA. The focus on ribonucleotides in origins of life research stems from its relevance to the "RNA World hypothesis". The idea was first formulated by Leslie Orgel (1), Francis Crick (2), and Carl Woese (3), proposing that life as we know it emerged from a simpler system based on RNA, which played the role of genetic information carrier as well as a reaction catalyst. It is proposed that, over time, these functions became more specialised. DNA, which is more stable than RNA, took over the role of storing genetic information, and protein, which has higher catalytic capabilities, took over the role of catalyst. There is a lot of evidence for RNA's early involvement in life's emergence. For example, if one takes a closer look at the structure of coenzyme A, a cofactor at the start of the tricarboxylic acid (TCA) cycle and lipid synthesis, one can recognise adenosine, one of the four ribonucleotides. In addition, X-ray crystallography reveals that the active site of ribosomes is made up entirely of RNA (4).
However, carbohydrates can be quite tricky to synthesise non-enzymatically (without the use of enzymes). The first reason lies in their structure. Stereochemistry refers to the relative arrangement of atoms or functional groups in 3 dimensions. (If you are unfamiliar with the term, I highly encourage you to check out this video on stereochemistry by Crash Course). Two molecules are stereoisomers when they have the same connections to the same functional groups but vary in the arrangement of those groups. A central concept in stereochemistry is chirality. If you place your hands together, you'll find that the fingers align. However, if you try to place one on top of the other, there is no amount of rotation that will align the two. Hence, your hands are chiral because they possess non-superimposable mirror images. A carbon atom connected to 4 different groups is called a chiral centre because you can draw a reflection of it where the groups don't completely align. A molecule with n chiral centres has 2^n stereoisomers.
(Professor Dave Explains have a great video on carbohydrates). Ribose, which has 5 carbons, 3 of which are chiral centres, there exist 7 other stereoisomers. For glucose, which possesses 4 chiral centres, there are 16. Depending on the arrangement of the OH group on the chiral centre connected to the CH2OH group at the end of the chain, the stereoisomers are further classified as D or L. For mysterious reasons we have yet to figure out, life as we know it only utilises D-sugars.
Biology does not struggle with making stereochemistry thanks to enzymes. When enzymes catalyse reactions, they bind to reactants in specific conformations and control how the reaction proceeds. However, it is unlikely, if not impossible, for enzymes to exist before the emergence of life, which makes stereochemistry a giant hurdle to overcome.
The second reason is their stability, or lack thereof. All carbohydrates have a carbonyl group (C=O) which is quite reactive. This is because oxygen, which is more electronegative, draws the electrons orbiting the carbon towards it, thus creating a positive charge on the opposite end. Molecules with electrons to spare, called nucleophiles, will donate a pair of electrons to the carbon, forming a covalent bond. This is what allows linear carbohydrates with five or more carbons to form a six-membered ring, called a pyranose, or a five-membered ring, called a furanose. This reactivity facilitates many other interesting chemical reactions, collectively called carbonyl chemistry. However, reactivity is a double-edged sword. Higher reactivity often comes hand-in-hand with less stability and can lead to faster degradation in harsh conditions.
In order to synthesise carbohydrates, prebiotic chemists often rely on two well-known reactions. The first one is the formose reaction, discovered by Aleksandr Butlerov in 1861 (5). The second one is a variation of the Kiliani-Fischer synthesis which utilises metal-cyanide complexes and UV light, discovered by John D. Sutherland's group in 2012 (6). In future posts, we will take a deeper look into these reactions!
"Carbohydrate"– Encylopedia of Astrobiology (https://link.springer.com/referenceworkentry/10.1007%2F978-3-642-11274-4_1748)
Article on Leslie Orgel written by Gerald Joyce (https://www.nature.com/articles/450627a)
Introduction to Stereochemistry by Crash Course (https://www.youtube.com/watch?v=Bw_cetheReo)
Introduction to carbohydrates by Professor Dave Explains (https://www.youtube.com/watch?v=wFYsufJ9XMM)
Introduction to the RNA World hypothesis by Nobel Laureate Jack Szostak https://www.youtube.com/watch?v=MPzWrv6l9l0
L. E. Orgel, J. Mol. Biol., 1968, 38, 381–393.
F. H. C. Crick, J. Mol. Biol., 1968, 38, 367–379.
C. R. Woese, The Genetic Code: the Molecular basis for Genetic Expression, Harper & Row, 1967.
N. Ban, P. Nissen, J. Hansen, M. Capel, P. B. Moore and T. A. Steitz, Nat. 1999 4006747, 1999, 400, 841–847.
A. Butlerow, C. R. Acad. Sci., 1861, 53, 145–147.
D. Ritson and J. D. Sutherland, Nat Chem, 2012, 4, 895–899.
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