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Complex Carbohydrates Illustrate the Design in Cells

Life requires information, and information is the product of mind. We know that DNA and protein structures are information-rich molecules. However, what is less known is that carbohydrates are perhaps the most information-rich molecules in the cell—making them evidence that life is the product of an intelligent Creator, and not of chance.

A faculty colleague of mine often joked that I was the “spaghetti scientist” because I worked at the Complex Carbohydrate Research Center at the University of Georgia. Spaghetti is made up of carbohydrates (one of the four classes of biomolecules), and eating spaghetti can be a “complex” process! However, carbohydrates have many more functions aside from giving us spaghetti. The National Academy of Sciences recently identified carbohydrates as having the following attributes:1

  • They are the most abundant organic molecules on the planet.
  • They carry more potential information than any other macromolecule.
  • Every cell on the planet is coated with a complex array of carbohydrates.
  • All cell-to-cell interactions take place via carbohydrates.
  • Most proteins, and some lipids, have carbohydrates attached to them that are important for their functions.
  • Eliminating any class of carbohydrates from an organism results in death.
  • Every human disease involves carbohydrates.
  • Altered cell surface carbohydrates are characteristic of cancer.
  • Many vaccines are carbohydrate based.

I will come back to some of these functions later, but first it is necessary to describe why carbohydrates have so much structural complexity.

Figure 1: The structures of alanine (left panel) and glucose (right panel). Each amino acid has two reactive sites: the carboxyl site (red) and the amino site (blue). Each hexose sugar has five reactive sites: the glycosidic site (red) and the hydroxyl sites (blue).

If we compare the alpha-amino acid building blocks of proteins with the sugar building blocks of carbohydrates, several things become apparent regarding the greater structural complexity of carbohydrates compared to proteins. Figure 1 compares the amino acid alanine with the sugar glucose, a hexose. First, while there are two possible structures for each of the 20 amino acids, there are eight different structures for each sugar (carbohydrates). Second, each amino acid has only two reaction sites, the carboxyl carbon and the amino group, while each hexose (e.g., glucose) contains five reaction sites, the glycosidic carbon and four hydroxyl groups. Due to the different combinations of attachment sites, a sugar allows for more possible linear polysaccharide or oligosaccharide structures than proteins do. Additionally, other sugars can be attached to any of the free hydroxyls of the linear structure, thus forming branched structures. Two amino acids can form 16 possible dipeptide structures, only four of which would be found in active proteins. However, the two sugars glucose (Glc) and galactose (Gal) can form more than 1,160 different disaccharides, and in principle, all of the disaccharide structures are possible in biological organisms. If a third L-amino acid is added, 27 tripeptides are possible, while the addition of a third hexose results in more than a 100,000 possible trisaccharides. Thus, the contrast in structural complexity between peptides and oligosaccharides increases dramatically with greater numbers of amino acids and sugars.

Obviously, if more than 100,000 trisaccharide structures are possible, then the number of possible oligosaccharide and polysaccharide structures is very diverse. Yet the cell requires specified structures for very specific roles, such as the following:

  • Mucins carry out important functions on the surfaces of the digestive, genital, and respiratory systems, permitting absorption of nutrients and functioning as lubricants and as barriers to pathogenic microorgansims.
  • Proteoglycan is a hyaluronic acid found in connective tissue, skin, cartilage, etc.
  • Chondroitin sulfate is an essential component in cartilage, the cornea, bone, skin, and arteries.
  • Dermatan sulfate is in skin, blood vessels, heart valves, etc.
  • Heparan sulfate comprises lung, arteries, and cell surfaces and is also important for controlling blood clotting.
  • Keratan sulfate is an essential component of cartilage and the cornea.

The cell also contains around 1,000 different oligosaccharide structures. Some form N-linked glycoproteins by attaching to the arginine amino acid in proteins. Others form glycolipids by attaching to lipids. These 1,000 structures have many essential functions, though they are a fraction of the millions of structural possibilities. They form different blood groups and are necessary for the development of multicellular organisms. During development, cells differentiate into various types of tissues, and the cells of each tissue type have a unique set of oligosaccharides on their surface. These oligosaccharide structures are also required for the localization of a protein to its site of action; an enzyme with one set of oligosaccharides attached is targeted to one tissue, while the same enzyme with a different set of oligosaccharide structures is targeted to a different tissue. Oligosaccharides also help the immune response, and they are involved in providing stability to proteins and function to some enzymes.2

What does it take for the cell to make a specific oligosaccharide structure from the millions of possible structures? Unlike proteins and nucleic acids, the carbohydrate structures are not “hardwired” in the cell’s DNA. Their structures are not template encoded and, therefore, not directly determined by the sequence of nucleic acids in the DNA. Instead, the genome DNA sequence contains information that results in about 100 proteins called glycosyltransferases (GTs). These are enzymes that add a sugar residue to a growing oligosaccharide or polysaccharide structure. It is the activities of a specific combination of these GTs that result in a specific oligosaccharide structure. The 1,000 or so different oligosaccharides require 1,000 unique combinations of GTs for their syntheses. Thus, one can think of the 100 or so GTs as a type of “glycocode” in which a specific oligosaccharide structure requires a correct combination of GTs to be active and also requires that these GT activities occur in the proper sequence.

Carbohydrates are essential for life, and it is their potential for complexity that provides for the necessary structures for life. Their structures require a hierarchy of different levels of information to determine just-right structures at the just-right time. The multiple layers of information required to produce the right oligosaccharide structures in the cell from the bewildering complexity of possible structures supports the conclusion that the cell is ultimately the product of a mind. This conclusion is consistent with the notion that the God of the Bible created life.

By Russ Carlson

Russ Carlson received his PhD in biochemistry from the University of Colorado in 1976. Now retired, Carlson was the technical director of the Energy-funded Center for Plant and Microbial Complex Carbohydrate Research Center since 1988. Carlson has also been a participant in RTB’s Visiting Scholar Program.

  1. National Research Council, Transforming Glycoscience: A Roadmap for the Future, (Washington, DC: The National Academies Press, 2012).
  2. Maureen E. Taylor and Kurt Drickamer, Introduction to Glycobiology, 2nd ed. (Oxford: Oxford University Press, 2006).