Nutrients and Solubility
The bulk of the food that we consume provides us with water, which accounts for 50% to 70% of our body weight, and the energy-yielding nutrients, such as carbohydrates (sugars and starches), lipids (fats), and proteins (Figure 1). In addition to these major nutrients, our bodies require a variety of other molecules and ions to maintain proper function. These nutrients, which are required in much smaller amounts, are known collectively as vitamins and minerals.
Carbohydrates, proteins, fats, and water account for most of our nutritional requirements. Vitamins and minerals are required in much smaller amounts, yet their contributions to the body's functioning are essential.
Fourteen vitamins have been shown to be essential for normal growth and health in humans. Vitamins are organic molecules (i.e., molecules containing the elements C, H, N, or O) that are needed in trace amounts to help catalyze many of the biochemical reactions in the body. The term "vitamin" derives from the words "vital amine," because the first vitamins to be discovered contained an amino group (-NR2, where R is a hydrogen or some carbon-containing functional group) in their molecular structure. The fourteen vitamins that we know today do not have any particular structure in common, nor do they share a common function, but they can be divided into fat-soluble (nonpolar) and water-soluble (polar) molecules. In general, vitamins do not themselves provide chemical energy or act as biochemical building blocks for the body. Many vitamins (e.g., the B vitamins) assist enzymes (act as coenzymes) in activities ranging from vision to growth ability. (Enzymes are proteins or other molecules that catalyze reactions, i.e., make them go faster, without themselves being permanently transformed. You will learn about more catalysts and enzymes in the "Kinetics" experiment and the related tutorial, "Drug Strategies to Target HIV: Enzyme Kinetics and Enzyme Inhibitors".) Other vitamins, such as the antioxidants (e.g., vitamin C, vitamin E), help to maintain structures within cells.
Plants and bacteria have the enzymes necessary to synthesize their own vitamins; however, animals do not have the ability to synthesize vitamins and must consume them in the diet. (One exception is Vitamin D, which we can synthesize from cholesterol if we get enough sunlight.) Hence, we obtain our vitamins by eating plants or meat (and diary products) from animals that have eaten plants.
Minerals are typically defined by nutritionists as inorganic (not C, H, N, or O) elements, which are used in the body to help promote certain reactions, or form structures in the body. This definition differs slightly from (is a subset of) the usual chemical definition of a mineral, which is a naturally-occurring, nonmolecular solid. (A nonmolecular solid has a lattice structure rather than discrete molecular units.) We will use the nutritional definition in this tutorial. Minerals are typically consumed in the form of a salt containing the mineral element and another ion. For example, the calcium in Tums is in the form of calcium carbonate (CaCO3). Minerals, like vitamins, perform a wide variety of functions in the body. Some, such as Mg2+ and Zn2+, enable enzymes to function, catalyzing biochemical reactions. Others, such as Na+, K+, Ca2+, and Cl-, help to maintain electrical and water balance in the body, transmit nerve impulses, and stimulate muscle contraction. Still others, such as Ca and P, form the compound hydroxyapatite that is responsible for bone growth and structure.
In order to use the nutrients that we take in when we eat, we must first break the food down into its nutritive components. These components are then either absorbed by the body, or they pass through the intestinal tract and are removed from the body in the feces. The nutrients that are absorbed pass through the lining of the intestinal tract into the blood. The blood carries these nutrients to the sites where they will be reassembled and used by the body. If the nutrients are not used immediately, they will either be stored for later use, or excreted in the urine. Each of these fates of the absorbed nutrients (immediate use, storage, or excretion via urine) requires that the nutrients be soluble. To be transported from the stomach to other parts of the body, the nutrients must either be soluble in water (the main component of blood plasma), or be solubilized by some other particles (e.g., proteins) that are carried in the blood. Nutrients that are stored in the body are typically stored in fat cells, so they must be soluble in fat. And of course, to be excreted via the urine, a nutrient must be water-soluble. Hence, understanding the solubility of nutrients in the different substances of the body is very important for understanding how they can be used or processed in the body.
Scientists have developed several ways to discuss the important concepts of solubility. For salts (ionic solids) that dissociate into ions in water, such as the compounds containing the dietary minerals, a solubility product (Ksp) is typically given. The solubility product is the equilibrium constant for the dissociation reaction of the compound into ions in aqueous solution. This quantity is useful, for instance, in determining which compound containing a given mineral is more soluble, and hence would be better absorbed as a dietary supplement (e.g., calcium carbonate vs. calcium sulfate). The solubility of organic molecules, such as the vitamins, is quantified using a different scale known as Hidebrand solubility parameters (which will not be discussed in this tutorial). Organic molecules may be soluble in water or in lipids, depending on the functional groups on the molecule. A vitamin's solubility in water or in lipids determines where it can be used, and whether it will be stored in fat cells or excreted from the body if it is not needed for immediate use.
The solubility of organic molecules is often summarized by the phrase, "like dissolves like." This means that molecules with many polar groups are more soluble in polar solvents, and molecules with few or no polar groups (i.e., nonpolar molecules) are more soluble in nonpolar solvents. (You encountered these concepts in the "Membranes and Proteins" experiment and the related tutorial, "Maintaining the Body's Chemistry: Dialysis in the Kidneys".) Hence, vitamins are either water-soluble or fat-soluble (soluble in lipids and nonpolar compounds), depending on their molecular structures. Water-soluble vitamins have many polar groups and are hence soluble in polar solvents such as water. Fat-soluble vitamins are predominantly nonpolar and hence are soluble in nonpolar solvents such as the fatty (nonpolar) tissue of the body.
What makes polar vitamins soluble in polar solvents and nonpolar vitamins soluble in nonpolar solvents? The answer to this question lies in the types of interactions that occur between the molecules in a solution. Solubility is a complex phenomenon that depends on the change in free energy (DG) of the process. For a process (in this case, a vitamin dissolving in a solvent) to be spontaneous, the change in free energy must be negative (i.e., DG<0). The green box below describes the thermodynamic processes that govern solubility.
Thermodynamics of Dissolution (Solubilization)
The dissolution of a substance (solute) can be separated into three steps:
The free energy (G) describes both the energetics (i.e., the enthalpy H) and the randomness or probability (i.e., the entropy S) of a process ( DG=DH-TDS, where T is the absolute temperature). The enthalpy and entropy changes that occur in the dissolution process are shown in Figure 2, below. In the dissolution process, steps 1 and 2 (listed above) require energy because interactions between the particles (solute or solvent) are being broken. Step 3 usually releases energy because solute-solvent interactions are being formed. Therefore, the change in enthalpy (DH) for the dissolution process (steps 1 through 3) can be either positive or negative, depending on the amount of energy released in step 3 relative to the amount of energy required in steps 1 and 2. In terms of the change in entropy (DS) of the dissolution process, most dissolution processes lead to a greater randomness (and therefore an increase in entropy). In fact, for a large number of dissolution reactions, the entropic effect (the change in randomness) is more important than the enthalpic effect (the change in energy) in determining the spontaneity of the process.
In general, if the solute and solvent interactions are of similar strength (i.e., both polar or both nonpolar), then the energetics of steps 1 and 2 are similar to the energetics of step 3. Therefore, the increase in entropy determines spontaneity in the process. However, if the solute and solvent interactions are of differing strength (i.e., polar with nonpolar), then the energetics of steps 1 and 2 are much greater than the energetics of step 3. Hence, the increase in entropy that can occur is not enough to overcome the large increase in enthalpy; thus, the dissolution process is nonspontaneous.
To illustrate the importance of DH and DS in determining the spontaneity of dissolution, let us consider three possible cases:
The principles outlined in the green box above explain why the interactions between molecules favor solutions of polar vitamins in water and nonpolar vitamins in lipids. The polar vitamins, as well as the polar water molecules, have strong intermolecular forces that must be overcome in order for a solution to be formed, requiring energy. When these polar molecules interact with each other (i.e., when the polar vitamins are dissolved in water), strong interactions are formed, releasing energy. Hence, the overall enthalpy change (energetics) is small. The small enthalpy change, coupled with a significant increase in randomness (entropy change) when the solution is formed, allow this solution to form spontaneously. Nonpolar vitamins and nonpolar solvents both have weak intermolecular interactions, so the overall enthalpy change (energetics) is again small. Hence, in the case of nonpolar vitamins dissolving in nonpolar (lipid) solvents, the small enthalpy change, coupled with a significant increase in randomness (entropy change) when the solution is formed, allow this solution to form spontaneously as well. For a nonpolar vitamin to dissolve in water, or for a polar vitamin to dissolve in fat, the energy required to overcome the initial intermolecular forces (i.e., between the polar vitamin molecules or between the water molecules) is large and is not offset by the energy released when the molecules interact in solution (because there is no strong interaction between polar and nonpolar molecules). Hence, in these cases, the enthalpy change (energetics) is unfavorable to dissolution, and the magnitude of this unfavorable enthalpy change is too large to be offset by the increase in randomness of the solution. Therefore, these solutions will not form spontaneously. (There are exceptions to the principle "like dissolves like," e.g., when the entropy decreases when a solution is formed; however, these exceptions will not be discussed in this tutorial.)
In general, it is possible to predict whether a vitamin is fat-soluble or water-soluble by examining its structure to determine whether polar groups or nonpolar groups predominate. In the structure of calciferol (Vitamin D2), shown in Figure 3 below, we find an -OH group attached to a bulky arrangement of hydrocarbon rings and chains. This one polar group is not enough to compensate for the much larger nonpolar region. Therefore, calciferol is classified as a fat-soluble vitamin.
This is a 2D ChemDraw representation of the structure of calciferol, Vitamin D2. Although the molecule has one polar hydroxyl group, it is considered a nonpolar (fat-soluble) vitamin because of the predominance of the nonpolar hydrocarbon region.
Table 1, below, shows the structures and functions of several fat- and water-soluble vitamins. To view a larger representation of the 2D and 3D structures, click on the name of the vitamin. To view and rotate the vitamin molecules interactively using RASMOL, please click on the three-dimensional structures for the coordinate (.pdb) file.
Coenzyme for collagen (connective tissue protein) formation; antioxidant; antibody production; hormone synthesis; cholesterol formation and excretion
Calcium and phosphorus absorption and regulation (needed for bone, teeth, and proper nerve function); some role in insulin secretion
(Part of the Vitamin B Complex)
Release of energy from food; manufacture of coenzyme A (needed for breakdown of fats and carbohydrates; production of neurotransmitters; hemoglobin production
Release of energy from food; synthesis and breakdown of amino acids; prostaglandin manufacture (needed for blood pressure regulation and heart function); skin and hair maintenance; hormone production
Vision; growth and repair of epithelial cells; embryonic development; production of myelin (nerve coating) and other membranes; immune system enhancement.
Tissue respiration; metabolism of carbohydrates, amino acids, and fats; growth and repair of body tissues; blood cell development and iron metabolism
Antioxidant (protects cells from toxic compounds, heavy metals, radiation, and free radicals); retinal development; protects vitamin A in eyes
The 2D representations shown in this table were drawn using CS ChemDraw Pro, and the 3D coordinates were obtained by MM2 minimization using CS Chem3D Pro.
Note: The 2D and 3D representations for each vitamin are drawn from the same view. The 3D (but not the 2D) representations are all drawn to the same scale. In the 3D representations, carbon atoms are gray, hydrogen atoms are light blue, oxygen atoms are red, and nitrogen atoms are dark blue. The coordinates for the 3D representations were obtained from molecular-modeling calculations, and the images were rendered using SwissPDB Viewer and POV-Ray (see References).
The solubility properties of vitamins determine how well they will be absorbed by the body. Water-soluble vitamins can easily enter the bloodstream by diffusion, since the stomach contents, extracellular fluid, and blood plasma are all aqueous solutions. Fat-soluble vitamins must be consumed together with dietary fat to be absorbed. The vitamins are first dissolved in the dietary fat. Then, bile released from the gall bladder acts like a detergent and allows the fat (with the vitamins dissolved in it) to be solubilized in micelles. (Recall the discussion of detergents and micelles from the "Membranes, Proteins, and Dialysis" experiment.) However, some newly-developed food products, unfortunately, have been found to disrupt this pathway for absorbing fat-soluble vitamins in the body.
In recent years, many types of "fat-free" foods have come into the marketplace. One such type of these foods contains artificial fats that are substituted for the natural fats and oils found in the foods. These artificial fats add no fat or calories to the diet, because they are not digested or absorbed by the body. The main artificial fat commercially in use is Olestra. Olestra is marketed under the name Olean by Proctor and Gamble, Inc. It is a synthetic sucrose ester that is not digested or absorbed by the body. How does this work? Olestra, like natural fat, has nonpolar hydrocarbon chains. But whereas fat has only three such chains attached to a glycerol molecule (and thus is known as a "triglyceride"), Olestra contains eight such chains attached to a sucrose molecule. (Refer to the figure on membrane structure in the "Membranes and Proteins" experiment for the structure of glycerol.) To digest natural fats in the body, lipase (an intestinal enzyme that breaks down lipid molecules) removes the hydrocarbon chains from the glycerol. The hydrocarbon chains are then emulsified (incorporated into micelles) with bile, and absorbed into the bloodstream. Because Olestra has so many hydrocarbon chains, there is not enough room for lipase to reach the place where they are attached to the sucrose, and so the side chains cannot be removed. Therefore, the nonpolar Olestra molecule is too large to form absorbable micelles, so it passes through the intestinal tract, undigested and unabsorbed by the body. Olestra has been approved by the FDA for use in savory snacks, such as potato chips.
Unfortunately, Olestra may not be as healthy as it first sounds. It has been shown to
cause gastrointestinal symptoms including abdominal discomfort, flatulence, and changes in
stool consistency. More importantly, it interferes with the absorption of fat-soluble
vitamins from food when present in the small intestine at the same time as other foods.
Because it is nonpolar, Olestra can dissolve fat-soluble vitamins. Hence, Olestra in the
small intestine competes with fat-containing micelles in the intestine for absorption of
fat-soluble vitamins. Anything the Olestra absorbs is carried out of the body with it and
is therefore not available for absorption by the body. Adding more fat-soluble vitamins to
food containing Olestra seems to be effective in preventing Olestra from depleting the
body's supply of fat-soluble vitamins. However, long-term studies are not yet conclusive
on the effects of continued ingestion of Olestra on humans.
- Examine the two-and three-dimensional structures of vitamin C in Table 1. Briefly, describe why vitamin C might have trouble permeating the membrane.
- Liu et. al. studied the effectiveness of vitamin C as an antioxidant. They synthesized a derivative of vitamin C called ascorbyl-6-palmitate and discovered that this derivative has increased effectiveness as an antioxidant in vitro (outside of biological systems). Below is the structure of ascorbyl-6-palmitate (Figure 4). Briefly, explain in terms of molecular structure and interactions why ascorbyl-6-palmitate should be more effective.
This is the 2D ChemDraw structure of ascorbyl-6-palmitate, which was synthesized by Liu et. al.
- Could this newly formulated vitamin C derivative, ascorbyl-6-palmitate, be added as a supplement, instead of "normal" vitamin C, to fortify fruit juices? Briefly, explain your answer.
Most minerals in the diet are in the form of water-soluble salts. When these salts dissolve, they dissociate into aqueous cations and anions. It is customary to describe the solubility of these salts (i.e., the solubility of minerals) quantitatively, as described below.
To quantify the solubility of the ionic salts containing dietary minerals, two distinct quantities are used: the solubility product, Ksp, and the solubility, S. (These are the same quantities that you determined for calcium hydroxide in the experiment.) The solubility product (Ksp) is the equilibrium constant of the dissociation reaction of the mineral-containing salt in water. Hence, Ksp is a constant at a given temperature. The solubility (S) of a mineral salt is the amount of the salt that is dissolved per unit volume. This quantity may vary, depending on the conditions. For instance, phytic acid from grain can bind to Zn2+ ions, making these ions unavailable to the body. Suppose that you take a zinc supplement in the form of ZnSO4. For your body to absorb the zinc, this compound must dissociate into Zn2+ and SO42-, as shown in Equation 1.
The equilibrium constant for this dissociation, Ksp, is a constant given by
the Law of Mass Action: Ksp = [Zn2+][SO42-].
If you also consume a large amount of phytic acid with the supplement, the phytic acid
will, in effect, remove free Zn2+ ions from solution. How does this affect the
solubility of ZnSO4? According to Le
Although the body's absorption of minerals depends in large part on their solubility, we must be very careful not to equate solubility of the salt containing a mineral with absorption of that mineral. In the example with zinc and phytic acid described above, the absorption of zinc decreases with phytic acid even though the solubility of zinc sulfate is increased. This is because the zinc is not present as the free ion in solution; rather it is bound to phytic acid and is therefore unavailable for absorption by the body. One way to overcome the problem of poor zinc absorption due to phytic acid is to eat leavened, rather than unleavened bread. When yeast is used to make bread rise, it destroys the phytic acid, and so the Zn2+ ions remain free in solution to be absorbed by the body.
Our bodies contain a staggering 1200 g of calcium. Only 1% of this calcium is in the body fluids (the extracellular fluid, the blood, and the cellular fluid). The calcium in the blood is important for a number of functions, including blood clotting, transmission of nerve impulses, muscle contraction, stability of cell membranes, and cell metabolism. The remaining 99% of the calcium in the body is contained in the bones in the compound hydroxyapatite, Ca10(PO4)6(OH)2. This mineral provides the structural integrity of the skeleton.
The calcium in the body fluids can exist in three forms: (1) as the free cation Ca2+ (about 50% of the calcium in the fluids), (2) bound to proteins (about 40% of the calcium in the fluids), and (3) complexed with other ions (about 10% of the calcium in the fluids). Of these three, the free cation is the most important for the physiological functions described in the paragraph above, and its concentration must be carefully maintained. For instance, muscle contraction is initiated by a sudden increase in calcium concentration in the muscle cells. Normally, this increase in Ca2+ concentration is triggered by a nerve impulse; however, if the "resting" Ca2+ concentration inside the muscle cells becomes too large, the muscles will contract without the internal nerve signal to trigger an increase in the concentration. The Ca2+ concentration in the extracellular fluid is kept at approximately 10-3 M, and the Ca2+ concentration inside the cells is kept at approximately 10-6 M. The body has several mechanisms to maintain these ion concentrations. The cells have channels and pumps that regulate the flow of calcium ions between the cells and the extracellular fluids via the cell membrane. In addition, the calcium ions can be removed from or bound to the calcium-binding proteins in order to increase or decrease, respectively, the free-ion concentration.
The two mechanisms for Ca2+-concentration maintenance described above
involve only exchange between the different forms of calcium storage in the fluids. What
happens if the overall amount of calcium in the fluids gets too low? In this case, calcium
can be supplied from two sources. (1) Calcium can be consumed in the diet, dissolved, and
absorbed into the blood. The normal calcium dietary requirement for an adult is
approximately 1 gram (1000 mg) per day. (Women and young people may need to consume even
more than 1 g of calcium per day.) (2) Calcium can be removed from the bones in order to
increase the Ca2+ concentration in the fluids. Hence, if too little calcium is
supplied in the diet, the body will take the calcium it needs from the bones. (Recall
equilibrium and Le
Hence, it is clear that we must consume an adequate amount of calcium in the diet in order to minimize loss of bone mass. But not all of the calcium that we consume ends up in our body fluids. In fact, we only absorb 30% of the calcium that we consume, on average. Several factors influence the absorption of the calcium that we consume. Two requirements must be met in order for calcium to be absorbed: (1) it must be dissolved in the intestine, and (2) it must pass through the intestinal walls into the body fluids. Some of the most important factors are listed below:
- The form of the dietary calcium affects calcium solubility. Different calcium salts have different solubility products and therefore different solubilities in the intestinal environment. Calcium citrate, for instance, is more soluble than calcium carbonate.
- The pH of the intestinal tract affects calcium absorption. Most of the calcium absorbed in the body is absorbed in the upper intestine, where the pH is low due to stomach acid entering the intestine. Calcium requires a pH of less than 6 in order to enter solution as Ca2+.
- Vitamin D stimulates intestinal calcium absorption.
- Parathyroid hormone (PTH) also promotes calcium absorption. (PTH has two major mechanisms for promoting the absorption of calcium: directly, by increasing Ca2+ reabsorption in the kidneys, and indirectly, by stimulating the activation of vitamin D.) When the concentration of Ca2+ drops, the parathyroid gland releases PTH to help bring the Ca2+ concentration back up.
The nutrients required by our bodies must be dissolved, and then absorbed by the body if they are to be used. The solubility of nutrients is determined by the molecular properties (e.g., polarity) of the nutrients. It is often useful to quantify the solubility of nutrients, in terms of the amount of the nutrient that is dissolved per unit volume. Although dissolution is a necessary step for nutrients to be absorbed, absorbance depends on more than the solubility of the nutrients. Certain substances in the digestive tract, such as Olestra and phytic acid, can interfere with the absorbance of some nutrients even if the nutrients are dissolved; other substances, such as vitamin D, can enhance nutrient absorption. All of these processes are governed by fundamental chemical properties and principles, such as polarity, molecular structure, intermolecular interactions, thermodynamics, and equilibrium.
Vitamin Update provides information about the functions of each vitamin in the body, as well as nutritional information on vitamin consumption, and periodic news updates on vitamin research.
The Olean promotional homepage provides access to a large body of research documenting the effects of Olestra consumption and how Olestra works. This informative site also contains a search engine to locate information of particular interest.
The Center for Science in the Public Interest maintains a web site warning about the health risks associated with Olestra consumption.
This site from Ball State University explains how the structure of Olestra allows it to taste like fat but not be absorbed by the body. It also includes interactive molecular representations that can be viewed using Chemscape Chime. To download CHIME, click here.
Virgin Earth (a supplement company) has an excellent site on minerals that contains a quiz to determine if you might be deficient in one or more minerals, as well as information about mineral interactions and mineral depletion from the soil.
Broadus, A.E. "Mineral Balance and Homeostasis," Ch. 9 in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 3rd ed., Lippincott and Raben, eds. American Society of Bone and Mineral Research.
Brown, T.L., H.E. Lemay, and B.E. Bursten. Chemistry, The Central Science, 7th ed., Prentice Hall, New Jersey, 1997, p. 466.
Guex, N. and Peitsch, M.C. Electrophoresis, 1997, 18, 2714-2723. (SwissPDB Viewer) URL: http://www.expasy.ch/spdbv/mainpage.htm.
Koonsvitsky, B. et al. "Olestra affects serum concentrations of a-tocopherol and carotenoids but not vitamin D or vitamin K status in free-living subjects," (1997) Journal of Nutrition, 127, 163966S-1645S.
Liu, X. et al. "Remarkable enhancement of antioxidant activity of vitamin C in an artificial bilayer by making it lipo-soluble," (1996) Chemistry and Physics of Lipids, 83, 39-43.
Persistence of Vision Ray Tracer (POV-Ray). URL: http://www.povray.org.
Schlagheck, T. et al. "Olestra's effect on vitamins D and E in humans can be offset by increasing dietary levels of these vitamins," (1997) Journal of Nutrition, 127, 1666S-1685S.
Stryer, Lupert. Biochemistry, 4th ed., W.H. Freeman and Co., New York, 1995, p. 452-455.
Wardlaw, G.W. and P.M. Insel. Perspectives in Nutrition, 3rd ed., Mosby, St. Louis, 1996.
The authors thank Dewey Holten, Michelle Gilbertson, Jody Proctor and Carolyn Herman for many helpful suggestions in the writing of this tutorial.
The development of this tutorial was supported by a grant from the Howard Hughes Medical Institute, through the Undergraduate Biological Sciences Education program, Grant HHMI# 71199-502008 to Washington University.
Revised January 2001.