The Nutrient Requirements of Cells

Introduction

• the bacterium E. coli
• human cells
• a unicellular green alga

As these lists show, mammalian cells are far more fussy than is E. coli. At first, this may seem perfectly reasonable: E. coli cells seem simple and mammalian cells seem complex.

But actually, little difference exists between them in the range and complexity of the macromolecules of which they are built. Both must make carbohydrates, proteins, DNA, and RNA from which they assemble cell membranes, ribosomes, and so on.

In a sense, E. coli appears to be more complex. It is able to manufacture molecules as complex as those of the mammalian cell, but using a far more limited range of starting materials.

• to supply all its energy needs from the potential energy stored in glucose and
• manufactures all of its organic molecules using the carbon atoms in glucose.
• NH₄Cl and MgSO₄ supply the nitrogen and sulfur atoms needed to synthesize proteins.
• Na₂HPO₄ and KH₂PO₄ supply the phosphorus atoms needed for nucleic acid synthesis (as well as being needed for the functioning of many proteins).
• These ingredients also supply the Na⁺, K⁺, Mg²⁺, and Cl^- needed by the cell.
• CaCl₂ supplies the needed Ca²⁺ ions.

All these ingredients are dissolved in water and are taken up from this solution.

Ham's Medium

The list of ingredients needed to grow human cells in culture is far longer.

• all 20 of the amino acids from which proteins are synthesized;
• a purine (hypoxanthine) and a pyrimidine (thymidine) for the synthesis of nucleotides, and their polymers DNA and RNA;
• 2 precursors (choline and inositol) needed to synthesize some of the phospholipids in the cell;
• 8 vitamins, all of which serve as parts of coenzymes;
• the coenzyme lipoic acid;
• glucose as a source of energy and carbon atoms;
• the inorganic ions Na⁺, K⁺, Ca²⁺, Cu²⁺, Zn²⁺, and Co²⁺ (E. coli may need some of these as well but in such tiny amounts that it can acquire them as impurities in the other ingredients of its medium.)

Even when all these ingredients have been mixed together, most mammalian cells still fail to grow unless some blood serum (e.g., from a human or a calf) is added. Just what metabolic need is met by this supplement is uncertain, but trace amounts of hormones in the serum are probably important.

Why does a mammalian cell require such a complex broth compared to E. coli? It is the price of multicellularity. A mammal is made up of hundreds of different cell types, each specialized to perform one or a few functions. All the many other functions of life — including the synthesis of many of the organic molecules it needs, it delegates to other cells. The extracellular fluid, derived from the blood, supplies it with these. Ham's cell culture medium is an attempt to recreate this extracellular fluid.

Bristol's Medium

This third recipe is used to culture green algae.

The most striking difference from the other two media is the item that is missing: glucose. In fact, no carbon-containing (organic) compound is included. This is because green algae, like all green plants, make the organic molecules they need by photosynthesis.

Green algae use the energy of sunlight to assemble inorganic precursors, chiefly carbon dioxide and water, into the array of macromolecules of which they are made. Such organisms are called autotrophic ("self-feeders").

The rest of us, who depend on organic molecules taken in from our surroundings are "heterotrophic".

Although heterotrophs may feed partially (as most of us do) or exclusively on other heterotrophs, all the food molecules on which we depend come ultimately from autotrophs.

• sources of nitrogen, sulfur, and phosphorus in order to synthesize proteins and nucleic acids;
• substantial amounts of magnesium (used to make chlorophyll), calcium, and potassium
• small amounts of Fe, Mo, Zn, B, and Cu.

Most of these micronutrients or trace elements are used in enzymes. Trace amounts of copper, for example, are incorporated in one of the enzymes used in photosynthesis.

There is an irony and an important lesson here. Copper sulfate (CuSO₄) is a widely used and potent algaecide; that is, an agent that kills unwanted algae (e.g., in municipal water supplies and swimming pools). But trace amounts of CuSO₄ provide an element essential to the life of these organisms.

This is one of many examples of substances that are poisonous above a certain concentration but essential at a lower concentration. So poisons may not be intrinsically poisonous. It is a matter of dose.