Carbohydrate Background

What is a carbohydrate?

Carbohydrates are also known as saccharides (Greek for sugar). From a basic structural standpoint, a carbohydrate is considered to be a “hydrate of carbon,” which basically means that for each carbon molecule, there is also one molecule of water. For instance, when considering the molecular formula for glucose, C6H12O6, we can rearrange it to C6(H2O)6 to indicate 6 carbon atoms and 6 water molecules. Carbohydrates can exist as simple sugars (monosaccharides), or as more complex sugars like sucrose (disaccharide) or starch (polysaccharide), which involve the polymerization of monosaccharide units.

Simple Sugars: Monosaccharides

Monosaccharides are the single sugar molecule building blocks. These often consist of 5-7 carbon molecules bonded together, though they can be assembled from as few as 2 carbons, or even 8 or more (these larger sugars are often unstable). Hundreds of different monosaccharides are known, and functions based on different locations and geometries of one carbonyl carbon (C=O) and several hydroxide (-OH) groups. If the monosaccharide has the carbonyl on the first carbon, then it will contain an aldehyde group (left structure), whereas a carbonyl on the second carbon makes a ketone group (right structure).

Monosaccharides often exist as ring structures due to a reaction between the aldehyde or ketone on one end of the carbon chain with a hydroxide at or near the other end, forming an ester-type linkage that is called a hemiacetal or hemiketal, respectively. This is a reversible reaction, and occurs rapidly and spontaneously (no enzyme needed) for most sugars when in aqueous environments. However, the cyclized (ring) form is usually the more prevalent configuration for sugars that form 5- and 6-membered carbon rings.

Four depictions of beta-D-glucopyranose (glucose) are shown above. The leftmost drawing is called a Fisher projection and draws a linear sugar molecule with the hydroxide geometries depicted by whether they project to the left or right of the vertical carbon backbone. The second drawing shows the process of cyclization between the carbonyl carbon (pink aldehyde in the first picture) and the penultimate (second to last) hydroxide. The formed hemiacetal is highlighted in blue.

The third drawing shows the cyclized sugar as a Haworth projection, where hydroxides pointing above the ring extend vertically upward from their carbon while hydroxides pointing below the ring extend vertically downward from their carbon. The final, fourth structure is the same sugar shown in a chair conformation, most similar to the three dimensional shape of the sugar. In both the Haworth projection and the chair conformation, the thicker line in the ring depicts the side of the ring coming out of the page toward you and the blue shape highlights the hemiacetal.

Structure Dictates Function

Different monosaccharides — glucose, fructose, etc. — may vary in the number of carbons, as well as the orientations of the -OH groups coming off of each carbon atom. Each particular set of orientations in 3-dimensional space creates a unique molecule, meaning sugar molecules can come in many different flavors — literally. The three dimensional shape of the sugar molecule affects how it interacts with taste receptors and metabolic enzymes so different sugars vary in sweetness and digestibility. For example, humans perceive fructose to be much sweeter than glucose, which is why it is added to corn sugar to create “high fructose corn syrup.”

Another example of how small molecular changes impacts function lies in DNA and RNA. DNA contains deoxyribose sugar, and RNA ribose sugar in their backbones — both deoxyribose and ribose contain 5 carbons, but differ in the absence (deoxyribose) or presence (ribose) of single oxygen atom. This seemingly small difference between the two sugars changes the stability and chemical reactivity of the different forms of genetic material.

Complex Sugars: Disaccharides to Polysaccharides

Monosaccharide building blocks can also bond together to formed from a pair of sugars (disaccharide) or a long or even branching chain of sugar units (polysaccharide). What we think of as table sugar (sucrose) is actually a disaccharide formed from the linkage of one glucose and one galactose, with an ester bond between them (highlighted in green). The geometry of the linkage formed between sugars is also important for metabolism. Another familiar disaccharide is lactose, which is found in dairy products. The specific linkage between the two sugar rings in lactose is digested by a unique enzyme called lactase, which is nots expressed in many adults populations throughout the world, causing wide-scale lactose intolerance.

The linkage between two sugar molecules is an example of dehydration synthesis, the same type of reaction as used to combine amino acids to make a protein. Also similarly, the reverse reaction, hydrolysis, breaks sugars back into monosaccharides.

Just as dehydration synthesis occurs repeatedly between subsequent amino acids to make proteins, this reaction occurs repeatedly to make long chains of sugars. This process is known as polymerization, where the units of assembly (in this case monosaccharides) are called monomers and the product of the polymerization reaction is a polymer (an oligosaccharide or polysaccharide). Unlike making proteins, there are many hydroxide (-OH) groups on a sugar that can participate in dehydration synthesis, so the polymers can be linear chains or or branched structures.

Polysaccharides are longer sugars and are most commonly used as energy storage in different organisms. Plants store energy as starch and cellulose, which are polymers of glucose. Humans can break the sugar-to-sugar linkages within starch, and thus we call this a digestible sugar. In contrast, we cannot break the linkages in cellulose and so we call this dietary fiber. Humans store energy as polymers of glucose called glycogen, which are heavily branched sugar structures.

Even within the categories of starches and fiber, there are many specific carbohydrate structures. In much of our food, starch is comprised of two main molecules: amylose and amylopectin. Amylose has a linear structure while amylopectin has a branched structure. These structural differences are important for the digestion of different starches, where enzymes hydrolyze sugars from the ends of polymer chains. Thus, the more highly branched amylopectin structure can be more efficiently digested than linear amylose.

Glucose Is An Ancient Source Of Energy

While there are multiple theories on the origin of biological life on earth, the exact mechanism for how life originated is still a puzzle that has yet to be solved. However, evidence does suggest that it took place approximately 3.8 billion years ago, at a time when the earth’s atmosphere contained little or no free oxygen (Precambrian). Consisting primarily of CO2 and N2, this primitive atmosphere provided the reducing conditions that allowed for the spontaneous formation of organic molecules, thus creating the “primordial soup” that set the stage for the first single-celled organisms.

Because the first single-celled organisms arose in a sea of organic molecules, they were able to obtain energy directly from their environment. However, this had limitations — given the rapidly changing ecological landscape of early earth, it became important for these first lifeforms to develop a more sustainable mechanism for generating the energy needed to grow and replicate. This process, which is central to all organisms to have ever existed on our planet, focused on the production of the most conserved molecule of all time: adenosine 5’-triphosphate, otherwise known as ATP.

As ATP evolved to become the driving force for nearly all energy-requiring cellular functions, so did the enzymatic cascades responsible for producing it. We believe that glycolysis — the cellular process of using glucose to produce ATP — was the first ATP-generating mechanism to arise. Evidence to support this includes the fact that it is present in all organisms and that it occurs in the cytosol of cells (does not need organelles). Furthermore, the enzymes involved in glycolysis display a significant level of evolutionary conservation across all known organisms, at the levels of function, structure, and sequence homology.

The Biochemistry of Glucose Metabolism

Glycolysis, which literally translates to “sugar splitting,” consists of a ten-enzyme cascade, where glucose (6 carbons) is broken down into 2 molecules of pyruvate (3 carbons). The process of glycolysis can be divided into 2 phases: the energy investment phase, which requires 2 molecules of ATP, and the energy output phase, which yields 4 molecules of ATP. This process, which nets 2 molecules of ATP, also results in the reduction of 2 NAD+ to 2 NADH. In addition to providing the cell with energy in the form of ATP, the reduction of NAD+ to NADH will provide an additional benefit for cells through its ability to donate electrons (reducing agent).

Once the process of glycolysis was established and early microbial cells had a mechanism to utilize the organic molecules around them to generate ATP (energy), the next step in the evolution of metabolism is thought to be the emergence of photosynthesis. By providing these early organisms with the capacity to convert sunlight into energy, photosynthesis released these cells from being reliant on the “primordial soup” to function, giving them energy independence. The by product of photosynthesis, O2, had the added benefit of changing the earth’s atmosphere, potentially giving rise to oxidative metabolism — a process where oxygen is used to convert carbohydrates into energy (as opposed to glycolysis, which can occur under anaerobic conditions).

Fast forward about 2 billion years, and glycolysis became fully and efficiently integrated with oxidative pathways. When oxygen is present, the 2 molecules of pyruvate generated as a result of glycolysis can be shuttled into the Krebs Pathway (also known as the Citric Acid Cycle), followed by the electron transport chain — both of which occur in mitochondria in eukaryotes. In total, the oxidation of glucose into carbon dioxide (cellular respiration) yields an approximate total of 32 molecules of ATP. With an efficiency that is more than an order of magnitude better than glycolysis alone, the process of cellular respiration allowed for an explosion of life forms, giving rise to the biodiversity seen throughout evolutionary history.