Principles of Biochemistry Volume 1 - A. Lehninger 1985

Biomolecules
Biochemistry: The Molecular Logic of Living Organisms
Living organisms are capable of precise self-replication

One of the most remarkable properties of living Cells is their ability to reproduce offspring of nearly identical precision over hundreds and thousands of generations. Three distinct features of this reproductive process deserve immediate attention. First, living organisms are so extraordinarily complex that it is difficult to fathom how the vast amount of Genetic information passed down from generation to generation can fit into the tiny Cell Nucleus where it is stored. We now know that all the genetic information contained in a bacterial cell is encoded in a single large molecule of deoxyribonucleic acid (DNA). Moreover, the far greater amount of genetic information packed into a single human germ cell is encoded in a set of DNA molecules with a total mass of only 6∙10^-12 g. This allows us to formulate yet another fundamental principle of the molecular logic of the living state:

Genetic information is encoded using structural units of submolecular dimensions; these units consist of four types of NUCLEOTIDES that make up all DNA molecules.

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Fig. 1-9. A single DNA molecule released from a lysed bacterium (Hemophilus influenzae). The DNA molecule is hundreds of times longer than The Cell itself.

The second remarkable feature of self-reproduction in living organisms is the exceptionally high Stability of the genetic information stored in DNA. Only a few ancient records have survived to the present day, even though they were etched into copper plates or carved in stone. For instance, the Dead Sea Scrolls and the Rosetta Stone, which provided the key to deciphering ancient Egyptian hieroglyphs, date back merely a few millennia. Yet there is every reason to believe that many modern Bacteria possess almost the exact same size, shape, internal Structure, and types of building blocks for enzyme molecules as the bacteria that lived millions of years ago. This constancy is maintained despite the fact that bacteria, like all other organisms, are subject to continuous evolutionary changes. Genetic information is not inscribed on copper or carved in stone; rather, it is stored in the form of DNA—an organic molecule so fragile that it shatters into numerous fragments simply upon stirring a DNA-containing solution or drawing it into a pipette.

Fig. 1-10. Complementarity between the coding elements of the two DNA strands.

DNA strands frequently break even within undamaged cells, but there they are rapidly and automatically repaired. The remarkable ability of living cells to preserve their genetic material is a consequence of structural complementarity. One DNA strand serves as a template upon which another structurally complementary strand is enzymatically built or repaired. However, despite the nearly flawless precision of genetic Replication, minor changes—Mutations—occasionally occur in DNA. These can give rise to either fitter, better-adapted offspring or, conversely, offspring less capable of survival. In this manner, living organisms continually enhance their survivability, with environmental shifts driving The Emergence of new species that undergo further evolution.

Fig. 1-11. Information stored as a linear sequence of nucleotides in DNA is translated into the three-dimensional structure of Proteins.

Let us examine the third remarkable characteristic of genetic Information Transfer in living organisms. Genetic information is encoded as a linear, one-dimensional sequence of nucleotides—the Building Blocks of DNA. Yet living cells possess a three-dimensional architecture and consist of three-dimensional components. The "one-dimensional" information contained in DNA is translated into the "three-dimensional" information characteristic of living organisms by converting the Introduction/20.html">DNA Structure into Protein Structure through The process of Translation (i.e., translation from one language into another). Ribonucleic acid (RNA) plays a central role in this process. Unlike DNA molecules, which share a largely uniform structural shape, molecules of different proteins spontaneously fold in characteristic ways to form a vast array of unique three-dimensional structures, each carrying out a specific function. The precise geometry of a given protein molecule is determined by its Amino Acid Sequence, which in turn is dictated by The nucleotide sequence of the corresponding DNA segment.

We can now summarize the fundamental principles of the molecular logic of cells:

A living cell is a self-assembling, self-regulating, and self-replicating isothermal system of organic molecules that extracts Free energy and raw Materials from its environment.

The cell maintains a multitude of sequentially ordered organic reactions accelerated by organic catalysts (Enzymes) produced by the cell itself.

The cell sustains itself in a steady dynamic state far from equilibrium with its environment, operating on THE PRINCIPLE OF maximum economy of components and processes.

The cell's capacity for nearly exact self-reproduction across numerous generations is ensured by a self-repairing system of linear coding.

The goal of biochemistry is to understand how the interactions of Biomolecules with one another give rise to the aforementioned Features of the living state. In examining the molecular logic of living cells, we have not once encountered a violation of established physical laws or the need to formulate any new ones. The "soft" organic mechanisms governing the operation of living cells obey the same set of laws that control human-made machines; however, the Chemical Reactions and regulatory processes taking place within cells are far more sophisticated and vastly surpass the capabilities of modern chemical technology.

While we recognize that the principles formulating the molecular logic of the living state are somewhat simplified and mechanistic, they appear to apply to all living cells. The question arises: can the molecular logic of the living state, as outlined here, be used to describe complex Multicellular Organisms, and especially the most highly organized forms of life? Can it be applied to the human Organism with its extraordinary and unique capacity for thought, speech, and creativity? We cannot yet even attempt to answer these questions, although we now know that the development and behavior of higher organisms are determined by molecular factors and modulated by them; consequently, they must have a biochemical basis. Nonetheless, we currently lack Answers to these more complex questions, as today's biochemistry is aware of only a tiny fraction of what remains to be discovered about living organisms.

In this General Overview, we have shown that biochemistry is not merely a collection of isolated chemical data regarding living matter, but rather rests upon a foundational framework comprising several crucial organizing principles. As we now embark on The Study of biochemistry, these organizing principles will serve as our primary guideposts. First, we will describe the various classes of biomolecules. Next, we will analyze the isothermal, sequentially linked, self-regulating enzymatic reactions that constitute METABOLISM—the system through which matter and energy are exchanged between the organism and its environment. Finally, we will examine the Molecular Basis of cell self-reproduction and The conversion of the "one-dimensional" information contained in DNA into the three-dimensional structure of proteins. Along the way, we will see how biochemistry contributes vital new insights into human physiology, Nutrition, and medicine, as well as a deeper understanding of plant biology, agricultural foundations, evolution, ecology, and the grand cycle of matter and energy linking the sun, earth, plants, and animals.