The 2,058th Meeting of the Society

March 29, 1996

Beginnings of Cellular Life

Metabolism Recapitulates Biogenesis

Harold Morowitz

George Mason University


In the absence of the President, Program Chairman Eloise Aggar called the 2058th meeting to order at 8:19 p.m. on March 29, 1996. The Recording Secretary read the minutes of the 2057th meeting and they were approved. Ms. Aggar introduced Harold J. Morowitz of George Mason University to discuss “Metabolism Recapitulates Biogenesis”. When you are given 45 minutes to cover 4.5 billion years of planetary history, you must either talk very quickly, or talk about about general principles. The most striking thing about early life on earth is how quickly it appeared. The best thinking is that the earth's surface cooled enough to permit life by about 4.5 billion years ago. There is some evidence of simple life by 4.13 billion years ago, and definite evidence for colonies of cells, stromatolytes, by 3.53 billion years ago. Every cellular form of life is based on paths of catalyzed chemical reactions referred to as metabolism. These pathways are used and regulated within cells to produce energy and reproduce the molecular components for the structures of life. The network of chemical reactions is usually presented in intricate charts of metabolic pathways. Certain core pathways are found in all cellular life forms and may represent metabolic reactions that could be performed by the most primitive life. These core metabolic pathways are virtual fossils. These metabolic pathways must have evolved in the environment of the primitive earth within the span from 4.5 to 3.5 billion years ago. By analyzing the metabolic pathways on the basis of how far each compound is from point where raw materials like carbon dioxide are incorporated a hierarchy of reactions becomes apparent. There are gateway reactions that permit access to additional shells of reaction pathways. We may have some clues to life's origins if we postulate that the hierarchy of reaction networks reflect a temporal ordering of reactions in biogenesis. There are two central pathways that conduct most of the chemical mass and energy flowing in these metabolic pathways between the basic energy store, the simple sugar glucose, and the raw materials carbon dioxide, water and free energy. These pathways, glycolysis and the citric or tricarboxylic acid (TCA) cycle, are found in almost all cellular life. Various life forms can run these reactions in either direction depending on whether glucose is to be stored or consumed to produce energy. In reducing enviroments the TCA cycle can be run in reverse to produce energy while taking up the raw material carbon dioxide, and a group of autotrophs has recently been discovered that make their living in just that way, incorporating all their carbon through the reductive tricarboxylic acid cycle. These organisms living in suitable reducing environment and running the TCA cycle backwards as an engine of synthesis provde a case study of this proposed primitive pathway. Certain key intermediates in the TCA cycle can be channeled through other biochemical pathways to synthesize the basic structural components necessary for reproducing life. The keto acids are used to make amino acids, acetic acid to make lipids, and pyruvic acid to make carbohydrates. Perhaps the unfolding origin of life flowed with the incorporation of the lowest energy state compounds, carbon dioxide and water, from simplicity to complexity. The development of complicated metabolic pathways followed the principles of evolving complex systems. In network systems it is difficult to change anything at the core successfully without changing many other things simultaneously in compensation. On the other hand it is easy to make changes and adaptations at the fringes, where failures are more tolerable and not as likely to be catastrophic. The principle of economic efficiency is “use what you've got and add to it”. Thus we can rationalize finding the same primary metabolism in all organisms, and variety in secondary metabolism with different organisms and tissues making different compounds using different reactions. We use this principle to map evolution onto biochemistry. Cellular life when it appeared must have had what we would recognize as primary metabolism. If cellular life appeared by 3.9 billion years ago, then life was probably there in a fairly sophisticated form of biomolecular reproduction within 100 million years of the surface of the earth cooling sufficiently to permit such molecules to exist. After that origin, life would have evolved by a series of frozen accidents. I am not a creationist but a determinist. Wherever there is carbon based life elsewhere in the universe it may well use the TCA cycle or something very like it. What reactions could have taken place before there were enzymes? Answers to this question are chemically testable. While the origin of the universe is not a laboratory experiment, and the origin of hominids and the human mind would be too slow to be a laboratory experiment, the origin of life is. Biogenesis is normative chemistry, and in fact, many of the most fundamental reactions have been preformed abiogenically in the laboratory since 1848 when Lebig succeeded in converting malic acid to fumaric acid. Mr. Morowitz kindly answered questions from the audience. Ms. Aggar thanked the speaker on behalf of the Society, announced the speaker for the next meeting, restated the parking policy, and adjourned the 2058th meeting at 9:24 p.m. Attendance: 51 Temperature: 5.2°C Weather: cloudy Respectfully submitted, John S. Garavelli Recording Secretary