Carbohydrates: A Biochemistry Crash Course
There are four major families of biomolecules: lipids, proteins, nucleotides, and carbohydrates. This guide focuses on carbohydrates and will examine their structures, production, and chemistry. There are a lot of terms use to describe carbohydrates, like carbs, starch, cellulose, and sugars. As you will see, these terms are not always interchangeable. Using them as if they were adds to the confusion within the field and can be detrimental to the health sciences. Whenever possible, use the correct nomenclature to describe carbohydrates.
Study tips. Most students first encounter carbohydrates in organic chemistry, specifically when discussing Fischer projections; these are two-dimensional representations of three-dimensional molecules as lines or sticks. Review these projections, as it is to common represent open-form carbohydrates as Fischer projections and closed-form carbohydrates as Haworth projections. Most courses will require you to know how to draw sugars in both forms and identify key substituents. Have a dry-erase board or notepad available to draw structures and commit them to memory. Conveniently, all carbohydrates share the same molecular skeleton; they only differ by the position of the stereogenic centers. Figures 1 and 2 show the common mono- and disaccharides found in biochemistry — these structures should be committed to memory.
Nomenclature and Structures
Carbohydrates and Saccharides
The term carbohydrate comes from the molecular formulas of all sugars. The general formula for carbohydrates is CnH2nOn, but another way to represent this is Cn(H2O)n. The carbon atoms within the sugars are hydrated with a water molecule, thus a carbohydrate.
The naming convention is to take the root structure and add the suffix –ose. A six-carbon carbohydrate is a hexose (the alkane root hexane): e.g., triose = C3H6O3, tetrose = C4H8O4, and pentose = C5H10O5.
Many of the biologically relevant carbohydrates are five or six-membered rings (pentoses and hexoses) and vary only by stereochemistry of the alcohol groups. Pentoses have three chiral centers, giving eight isomers (23), while hexoses have four chiral centers, giving 16 isomers (24). All of these structures have common names; you should become familiar with the most common ones (Figure 1). Hexoses can also have aldose and ketose form (Figure 3), which is determined by the position of the carbonyl.
Other terms for carbohydrates are saccharides or sugars. Saccharides can be either the anionic salts of sugars or a general synonym for carbohydrates. The term is often used when discussing the number of rings: monosaccharide (one ring), disaccharide (two rings), and polysaccharide or oligosaccharide (many rings). In biochemistry, sugar is a generic term to describe any carbohydrate, but should not be confused with common table sugar. Table sugar is sucrose—a disaccharide made up of glucose and fructose (Figure 2). Common names exist for the most prevalent disaccharides, like maltose (glucose-glucose), lactose (galactose-glucose), and sucrose (glucose-fructose). An example of its usage is, ‘the transport protein binds to the sugar motif of the glycoprotein and transports it to the lysosome.’
The prefix glyco- is used in biochemistry to refer to sugars and their processes. Glycogen is a stored form of glucose, glycogenesis is the process of storing glucose, glycolysis is the breakdown of glucose for energy, and glycoprotein is a protein that is decorated with a sugar motif. When a large number of monosaccharides are linked together, they can be referred to as a glycan, an amylum, or with the lay-term starch. Glyco- is derived from the sugar glucose.
Carbohydrates are depicted two different ways: (1) as a linear Fischer projection, or (2) as a cyclic Haworth projection (Figure 1). In most courses, students are required to identify the sugars in both forms and learn how to interconvert between the cyclic and open-chain form. Figure 4 demonstrates the process for D-glucose. Note that the penultimate carbon is the next-to-last carbon or last stereogenic carbon in the Fischer projections. For a hexose, it is carbon-5; for a pentose, it is carbon-4.
To draw the cyclic Haworth project, first write the linear Fischer projection with the carbonyl carbon at the top. Label the carbons starting at the carbonyl; any carbons that precede the carbonyl carbon are not labeled (i.e., fructose from figure 1). Turn the structure on its side with the carbonyl carbon on the right. The mechanism for cyclization begins by deprotonation of the alcohol on the penultimate carbon in the chain. The resulting oxide is a strong nucleophile and will attack the carbonyl electrophile. The alcohol at position-1 can be either above or below the ring, see below. The alcohols on the bottom of the turned Fischer projection (positions 2 and 4 of figure 4) will be below the horizontal plane of the ring while alcohols on the top will be above the plane (position 3 of figure 4). Remember this phrase: carbs are downright uplifting. Looking at the Fischer projections, alcohols on the left will be up or above the ring (up-left), while alcohols on the right will be down or below the ring (down-right).
All carbohydrates are optically active. Each carbon within the ring is a stereogenic center. There are two carbons that should be focused on immediately. Carbon-1, known as the anomeric carbon, determines α- or β-, while the penultimate carbon determines D– or L– configuration.
When cyclization occurs, the carbonyl in the straight chain is converted to an alcohol. This alcohol can be position above the plane of the sugar ring (β-) or below the ring (α-) (Figure 5, left). In chemistry, similar molecules that differ at one position are known as epimers, but, in carbohydrate chemistry, they referred to as anomers. The stereochemistry of the anomeric carbon has implications on di- and polysaccharide formation as well as how sugars bind to enzymatic pockets.
The D– and L– configuration is determined by the last stereocenter in the Fischer projection, which is the carbon that bears the -CH2OH group. If the CH2OH group is above the plane of the sugar, it is a D-sugar (Figure 5, right). In biochemistry, you will primarily encounter D-sugars, as their usage is conserved throughout biology. Also, note the convention that the D– is both capitalized and subscripted when written out. In figure 1, the top two carbohydrates are β-D-ribose and α-D-glucose.
Monosaccharides can be joined to other saccharides via an ether linkage known as an O-glycosidic bond. The three most common disaccharides are found in Figure 2. Figure 6 focuses on maltose and highlights the glycosidic bond between two glucose molecules. In the Haworth projections, it is common to see extra vertices within the bond, but they are not carbon atoms (Figure 6, left). This is done so that the figures will fit conveniently within the pages of a book. A better depiction of the molecule would be the boat-form of a six-membered ring (Figure 6, right), but these types of figures, though accurate, are difficult to recognize.
The convention for naming disaccharides (or poly-) is left to right, designating the absolute stereochemistry, and showing the carbon atom linkage. For maltose (common name), the molecular name is α-D-glucose-(1→4)-α-D-glucose. The α-1,4 linkage is common in glucose storage, as are α-1,6 linkages.
Starches are long chains of polysaccharides that can be linear or branched depending on the linkage (Figure 7).
Special note. Not all sugars are sweet. Sweetness is a response from the tongue when certain sugars (e.g., sucrose, fructose, maltose) or amino acids touch it. What determines sweetness is whether a molecule can fit in the appropriate receptor, and this is determined by the sugar’s global stereochemistry. Lactose and some starches are quite bitter.
Glucose Production and Storage
Glucose is one of the most widely-used carbohydrates in living organisms. It is used as the primary energy source throughout biology; find our glycolysis and Krebs cycle study guides for more on those processes. Animals acquire glucose and other sugars in the foods that we eat. Plants and other photosynthetic organisms use light to convert ambient CO2 and water into sugars and oxygen.
Photosynthesis is a series of enzymatic reactions that require a separate study guide. An overview is provided in Figure 8. Photosynthesis occurs in the chloroplasts, organelles that are filled with the light absorbing pigment chlorophyll. The reactions are split into light-dependent reactions and light-independent reactions. The overall chemical equation is: 6CO2 + 6H2O + photons → C6H12O6 + 6O2
As a plant produces glucose, it can use the carbohydrate immediately, store the material as starch granules, or use it as a building material for cell walls. Green plants and algae have cell walls composed of cellulose. Cellulose is world’s most abundant oligosaccharide; it’s a polymer of β-(1→4) O-linked D-glucose molecules. Due to the β-configuration, the starch is a straight chain that many animals cannot digest. Ruminants rely on symbiotic microorganisms in their gut to aid in digestion. Humans refer to cellulose as dietary fiber — it passes through the gut undigested and aids in defecation.
The plant also stores the glucose as starch granules that are α-(1→4) linked glucose molecules with branching α-(1→6) linkages every 30 sugar monomers. The starch has more kinks and turns, unlike cellulose. This polysaccharide is fit for human consumption, digestion, and absorption of glucose.
Humans store glucose in the liver and muscles as glycogen (Figure 9). Similar to starch molecules in plants, glycogen is an oligosaccharide of α-(1→4) linked glucose molecules with branching α-(1→6) linkages every 10 glucose monomers, making a more compact starch globule. At the core of the globule is a protein called glycogenin that catalyzes the addition of glucose molecules to itself.
Humans must maintain strict blood-glucose levels. However, when carbohydrates are in short supply, the liver and kidneys can initiate a metabolic pathway known as gluconeogenesis (GNG). This pathway can generate glucose from non-carbohydrate carbon sources like amino acids and lipids. Many of the transformations are similar to those found in the glycolysis pathway and are reversible reactions. The three high-energy steps within the glycolysis pathway (hexokinase, phosphofructokinase, and pyruvate kinase) are replaced with kinetically favorable enzymes (glucose-6-phosphatase, fructose-1,6-biphosphatase, and PEP carboxykinase). Overall regulation of the GNG pathway is done by glucagon, discussed below.
Regulation of Blood Glucose
Blood glucose levels are regulated by two opposing hormones: insulin and glucagon (Figure 10). After a meal, blood glucose levels are high (hyperglycemia) and in response the pancreas secretes insulin. At the liver’s initiation, the cells take in glucose and store it as glycogen. Through this process, insulin acts to lower blood sugar level. When blood glucose levels fall below normal levels (hypoglycemia), the pancreas secretes glucagon, triggering the mobilization of stored glucose from glycogen. Diabetes is the disease in which the pancreas either cannot produce enough insulin or the insulin produced is impaired, resulting in abnormal carbohydrate metabolism.
Carbohydrates perform various roles in biology. We’ve discussed how they are stored and used as a source of energy, and how they are used as a structural support in cell walls. Carbohydrates are also used by cells to communicate with one another. Cell membranes are often decorated with glycoproteins that the body can recognize as either being native cells or foreign pathogens.
The ABO blood groups seen in Figure 11 are a product of carbohydrate chemistry. The red blood cells are coated with glycoproteins that are identified as being antigen A, antigen B, antigen AB, or antigen O. The antigens differ by the presence or absence of specific carbohydrates.
Carbohydrates can also be found within our genetic material. The “R” in RNA stands for ribose (Figure 1), while the “D” in DNA is deoxyribose. The difference between ribose and deoxyribose is that the alcohol on carbon-2 of deoxyribose is missing. That one alcohol has a major implication for the stability of the molecule. A DNA molecule is stable for decades, while RNA molecules easily hydrolyze.
As you can see, there is a lot of information when it comes to carbohydrates and why it is important not to use blanket terms. There are many nutritional websites that get carbohydrate chemistry wrong. Carbohydrates are a necessary part of the diet, as they are needed to maintain proper biochemistry throughout the body. Of course, all things should be taken in moderation, even sugars, as diseases like diabetes or obesity are the result of overindulging. When in doubt, use the best term to describe the system you are dealing with.
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