EVOLUTION OF PROTEINS

EVOLUTION OF PROTEINS

What are proteins?

Proteins are polymers or combinations of various amino acids called peptides when they are bound in a chain.  A tri-peptide is composed of three amino acid residues, polypeptides of multiple ones; proteins have residues numbering in the hundreds and more.  Each amino acid incorporates a nitrogen atom in its structure at the site where it can be combined with the acid-like part of another amino acid, leaving similar junction sites on the resulting molecule so longer chains can be produced.  Further linkages via side chains can yield a great variety of shapes.

Why are proteins important?

They are the key to much of the structure and function of an organism.  Many of them are common to other distantly related species.  Some are unique to a species and even individuals or a subgroup of a species.

The proteins of our body have great diversity based on variations in the sequence and the resultant structure.  Enzymes are proteins useful in aiding chemical processes of the body.  Insulin is a protein type hormone.  Enzymes and hormones vary greatly in size but are typically much smaller than proteins used for structural purposes.  Both enzymes and hormones typically have their activity based on a peculiar aspect of their structure, often just a small portion of the molecule – the active site.

Hormones cause cells or organs, in various specific locations away from the sites of hormone production, to do their jobs.  Enzymes typically enable a chemical reaction to occur with minimal energy expenditure and can do so repeatedly.  Cooking deactivates enzymes and prevents decomposition until other organisms digest or invade the cooked food.

 Myosin and actin are two major proteins of muscle and each has a filament type structure. Large bundles of myosin slide past smaller bundles of actin and cause muscles to shorten and do their work.  Opposing muscles contract to cause the extension of an opposing relaxing muscle by force applied through the mechanics of the skeleton or tissue fluidity.

What evolutionary affects did the nitrogen atom of amino acids have?

When an amino acid or peptide is broken down the nitrogen atom can be released as an ammonium molecule, a toxic substance if concentrations build up in the body.  Most carbohydrates and lipids do not contain nitrogen so their residue, after use for energy, is carbon dioxide and water.  So is much of the protein but the ammonia cannot be passed into the air from fluid in the lungs very effectively.  Aquatic animals were able to accomplish much of the early evolution of life without needing special organs to dispose of nitrogenous waste.  The ammonia could diffuse from the body surface or gills into water where it would be useful for plants.

As organisms got larger those that could package ammonia into less toxic forms had an advantage.  Urea and uric acid are two of the substances that were selected for most successful animals.  Urea is soluble in water but non-toxic; it is the major compound containing nitrogen that is excreted by the mammalian kidney.  Uric acid is toxic but not very soluble and it is the main product produced by degradation of adenine and guanine from the nucleic acids, DNA  and RNA.  Biochemical processes in animals are varied in their potential to make various conversions of nitrogenous wastes.  Along the way, kidneys became more and more important for regulating levels of nitrogenous wastes in the blood as well as salt and water balance while retaining nutrients.

Uric acid made it possible for shelled eggs of animals to evolve for life on land.  It could accumulate in the egg without poisoning the embryo.  That made it possible for reptiles to lay their shelled eggs on land.  Birds continued the egg-laying process, as did early mammals (the platypus and echidna still do).  Eventually placental mammals developed and transferred nitrogenous wastes from the fetus to the mother for elimination by her kidneys. 

Why didn’t birds go that route?  Probably it has weight reducing value for flight.  It’s so important that only one ovary develops in a female bird, probably enabling larger eggs to be laid that can develop to greater maturity.  You can probably think of the survival advantage a mammal has from being able to takes its internal young with it and not be bound to a nest location and its hazards.

Proteins and the pharmaceutical industry

Hormone and enzyme activity must be well regulated by the body for health.  Too much or too little function can be detrimental to health.  Some classes of drugs are designed to have function like those items in the body.  They can supplement the body’s product or interfere with its function as needed to get the correct balance.  The critical aspect is getting an active site incorporated in a non-toxic molecule that can go to the needed area.  Alternatively, a toxic molecule designed for attraction to a cancer cell or overactive gland might be helpful.

Trial and error methods are being replaced by analysis of molecular structure for duplication of active sites in a synthetic substitute.  The active site in some cases is not dependent upon the chemical nature as much as the physical shape of the portion of the molecule.  Other parts of the molecule may affect some part of the process so clinical trials are needed to verify safety and effectiveness.

Unfortunately all possible interactions, with systems of the body at all stages of function and development, breakdown products and their role in the environment, and other possible hazards cannot be foreseen.  But we hope care in the process can minimize the hazards.

The computerized process of designing molecules based on fit with some portion of hormones, enzymes, cell membrane receptors or other entities is a likely source of valuable products.  But individuals and/or conventional research teams cannot be replaced as easily for less conventional and serendipitous discovery.

Joseph G. Engemann                April 30, 2014