Biology Review

I want to give a brief overview of some organismic biology before we begin our discussion of toxicology. One of the sacrifices made by organisms when they become multicellular is a loss in surface area for exchange vs. volume. Thus multicellular organism must create special organs with large surfaces for exchange of nutrients, gases etc. Of course these surfaces also allow the exchange of toxicants. Lets look at the major organ systems involved in exchanges with the environment:

• We can begin with the gastrointestinal tract:

  

   

  Just to put things in perspective we should note that the gastrointestinal tract is like the hole in a donut - things in the digestive tract are not inside of your body. Thus, in the figure the esophagus, the stomach, the small intestine, the large intestine, the gall bladder, and the worm-like appendage (appendix) are all segments or dents in the hole in the donut. All of these organs provide exchange surfaces. The gall bladder is excretory: it both excretes wastes (including toxics) and it provides detergents to aid in digesting fats and oils. The remaining organs will be mostly ingestion. Where a chemical will enter this system will depend on the relative surface areas, the nature of the surface, and the conditions in the compartment. Thus the small intestine is by far the most important absorbing organ for most things because it is very long, increasing its relative surface area, but more important, its surface is tremendously increased by microscopic villi (finger-like projections made up of many cells), which in turn have microvilli (finger-like projections from individual cells). Factors such as pH also influence absorption by changing the polarity of chemicals and making them more or less soluble in membranes. The pH in the stomach can be very acidic, for example in carnivores around pH 2, while the pH of the small intestine is often slightly basic, around pH 8.

  

   

• Next we can look at the respiratory system:

  

   

  The respiratory system consists of a long tube, the trachea, which then branches repeatedly down to the very fine bronchioles which end in the tiny alveoli (sacs):

  

   

  This system provides a tremendous surface area for gas exchange. Again different parts of this system will be major points for exchange or damage by different toxins. Here one major factor is the relative solubility of a toxin in aqueous fluids (very soluble substances will dissolve early and thus not get far down the system, localizing damage and/or exchange to the trachea, low solubility substances may reach all of the way to the alveoli where most exchange will take place due to the larger surface for interaction and lesser surface coating). A second factor for point of action is particle or aerosol size. Larger aerosols/particles will be trapped in the trachea, whereas very fine particles/aerosols may reach down into the bronchioles etc.

• A third major system for exchange and potential damage is the urinary system. This system is used for excretion. It is subject to high exposure to some toxins because so much of the blood circulation passes through the kidneys, and of course the kidneys then concentrate various substance for excretion. The kidneys also have a high level of metabolic competence like the liver, and thus toxify some compounds. The overall metabolic effect of the kidneys is relatively low however, because of the large difference in size between the liver and the kidneys. Thus most metabolic transformation will take place in the liver.
• Finally, a very obvious surface for exchange is the skin. Note that the outer "horny" layer of the skin is dead, so exposure is only a problem if this outer layer is penetrated. As aqueous organisms exposed to a largely aqueous environment, the skins outer layer is designed to be most resistant to polar molecules. Thus the skins (or outer surfaces) of most organisms are rich in lipids (oils and waxes) which are excellent barriers to aqueous solutions and polar molecules. On the other hand, non-polar molecules, like the oily toxin of poison oak, penetrate easily. However, these toxins are then mostly confined to the skin itself, since they are not soluble in the aqueous environment of the body itself! So there is, in a sense a double barrier.

Cells and Cell Compartments

Look at handout/overhead on compartmentation of cells.

Eukaryotes differ from prokaryotes in having a nucleus and cell organelles (their cells are physically compartmentalized). As a point of reference, an E. coli (bacterial) cell is about the size of a typical mammalian mitochondria.

• Cytosol: Glycolysis and most of gluconeogenesis; Pentose Phosphate shunt; Fatty acid biosynthesis.
• Mitochondria: Kreb's Citric Acid Cycle; Electron transport system and Oxidative Phosphorylation; Fatty acid oxidation; Amino acid catabolism; Interconversion of carbon skeletons.
• Endoplasmic Reticulum: Lipid Synthesis; Steroid synthesis; Phase one detoxification reactions; Biosynthesis and modification of membrane and export proteins.
• Golgi Complex: Further modification of membrane and export proteins.
• Lysosomes: Hydrolytic (digestive) enzyme localization.
• Peroxisomes: Amino acid oxidases, catalase-oxidative degradation reactions.
• Nucleus: DNA replication, synthesis and processing of messenger RNA's.
  • Nucleolus: localized region of the nucleus in which ribosomal RNA's are synthesized and processed.
• Plasma Membrane: Active and passive transport systems; receptors and signal processing systems (synthesis of various second messengers etc.).
• Ribosomes: protein synthesis (associated with ER for membrane and export proteins).

Last modified 22 January 2010

© RA Paselk 2001