By Paul B. Brown
Dr. Alan Perlis was a mathematics professor at Purdue, Carnegie Mellon, and Yale Universities and considered one of the pioneers in computer programming languages. His quote describing complexity refers to his area of research and the complex interactions between computers, but the concept of complexity also applies to nutrition.
Those of us who work in nutrition do not ignore the complexity of our chosen discipline, so I suppose we are not as foolish as some might argue. However, I fear we have not removed much of the complexity either, so I suspect few would accuse us of being geniuses. All biological processes are inherently complex and nutrition is not an exception. The following is an example of this complexity.
Methionine is one of the essential amino acids in animals, and first limiting in many formulations for fish and crustaceans. One of the clearer descriptions of limiting amino acid is to envision a wooden barrel made from narrow wood slats held together with metal bands, similar to wooden barrels or casks used to age various beverages, such as wines and whiskeys. If just one of the wooden slats is broken, the barrel can only hold liquid to the point the one slat is broken. It does not matter that all of the remaining slats are complete and intact. Similarly, if any of the essential amino acids are present in insufficient concentrations in the diet, the animal can only grow up to the level supported by the concentration of the limiting essential amino acid; i.e., not 100% of their biological potential. Again, it does not matter that all other essential amino acids are provided in adequate concentrations.
One of the fundamental challenges in nutrition is how to meet limiting essential amino acid requirements. One of the more obvious solutions is to use ingredients that contain higher concentrations of the limiting nutrient, in this case methionine. However, methionine is present at low concentrations in most feedstuffs. Genetic selection of crops that contain higher methionine concentrations or transgenic plants that synthesize higher concentrations of methionine are options, but have not met with much success. Feed grade methionine sources are commercially available and are commonly added to many animal feeds and we will consider those in future articles. Another approach is to understand the complex interactions of methionine with other nutrients.
Methionine interacts with several other nutrients and adding those nutrients in diets may “spare” and perhaps reduce the methionine requirement. The most commonly studied sparing of methionine has been with the nonessential amino acid cysteine. The biochemical basis for cysteine sparing of the dietary methionine requirement lies in metabolism of methionine within cells. One of the early breakdown products of methionine is cysteine (Fig. 1). If the cellular cysteine needs are provided by a dietary source, methionine can be spared for other uses, such as protein synthesis and growth via synthesis of S-adenosylmethionine (SAMe, forcing methionine to the right and left in Fig. 1, where we see its role in growth). Sparing methionine for protein synthesis is one of the goals of dietary formulation, particularly for food animals.
In fishes, cystine can spare 40-60% of the methionine requirement. Estimates of the cysteine sparing percentage have been published for channel catfish, red drum, hybrid striped bass, yellow perch, and Nile tilapia. For example, if the dietary methionine requirement is 1.0% of the diet, using ingredients that contain 0.5% methionine and 0.5% cystine may meet the requirement. In diets for yellow perch, the methionine requirement was actually lower when methionine + cysteine was provided supplemented into the diet at the experimentally determined maximum sparing concentration of 51%. Two of the three response parameters indicated a lower methionine + cysteine requirement than the methionine requirement with minimal cysteine; 0.85-1.0% of the diet as opposed to 1.0-1.1% of the diet.
This finding is intriguing, but needs to be examined further in additional species. Additional nutrient interactions exist with methionine that may further reduce the challenges associated with meeting the dietary requirement.
Several additional nutrients are involved in methionine metabolism (Fig. 2), specifically the vitamins folic acid (folate), vitamin B12 (cyanocobalamin), vitamin B6 (pyridoxine) and choline. Potential practical importance lies in the reduction of methionine catabolism (breakdown) into SAMe and the synthesis of methionine from homocysteine (hCys). The left side of Fig. 2 depicts synthesis of methionine from hCys using a folic acid metabolite, the right side depicts methionine synthesis from hCys using choline and the metabolic intermediate betaine (Note: betaine is both a flavor additive in diets fed to aquatic animals, and an osmolyte, reducing osmotic stress in euryhaline species transferred between salinity concentrations). Both remethylation reactions occur in vertebrates, but the extent and biological significance have not been fully elucidated in the fishes. Anecdotal evidence suggests there is a link between dietary choline and betaine intake with methionine status in tilapias, but there is much work to do in this area; largely because of the complexity of the biochemical interactions.
Another quote from Dr. Perlis appears appropriate as we consider the practical significance of the complexity discussion above, “Simplicity does not precede complexity, but follows it”.
Methionine, folic acid, vitamins B12 and B6, and choline are all essential nutrients in animals and must be supplied in the diet at appropriate concentrations and appropriate ratios to each other. Perhaps the best ingredients for meeting these requirements in aquatic animals are marine-derived protein feedstuffs; eg. fish meal. However, increases in the supply of fish meal are unlikely and demand for fish meal is increasing, placing upward pricing pressures on this commodity. Other feed ingredients contain the essential nutrients discussed above, but at different, most often lower, concentrations than found in fish meal. As fish meal is continually replaced in diets for aquatic animals, supplementation of critical nutrients becomes increasingly important.
One of the primary challenges for formulating diets in the 21st century is meeting the unique nutritional requirements for the target species and understanding the complex interactions that occur once the target species consumes the feed. Confounding this challenge is the inevitable changes in major dietary ingredients. There is much work to do in this area, but we are moving away from the inherent complexity in this biological system toward a more thorough understanding and the simplicity we desire. Historians will decide if we achieve sufficient simplicity to be declared geniuses.
Dr. Paul Brown is Professor of Fisheries and Aquatic Sciences in the Department of Forestry and Natural Resources of Purdue University. Brown has served as Associate Editor for the Progressive Fish-Culturist and the Journal of the World Aquaculture Society, among many others.