lOMoAR cPSD| 3013804
1 Bioc385 Foundations TEXT
Metabolic Biochemistry (University of Arizona)
lOMoARcPSD|301 380 4
Miesfeld & McEvoy Biochemistry – DRAFT
WW Norton Publishers, New York, NY
Chapter 1 – Foundations in Biochemistry (short version)
Lecture 1. Foundations in Biochemistry
HAT IS BIOCHEMISTRY?
HE CHEMICAL BASIS OF LIFE: A HIERARCHICAL PERSPECTIVE
Elements and chemical groups commonly found in
nature
Four major classes of small biomolecules are present
in living cells
Macromolecules can be polymeric structures
Metabolic pathways consist of linked biochemical
reactions
Structure and function of a living cell
Grapes and barley are the sources of sugar and
Cells communicate by signal transduction
natural flavors that are metabolized by live yeast cells
The biochemistry of ecosystems
to produce alcoholic wine and beer, respectively.
Biochemistry in Real Life
In the late 1800s, chemists in Europe sought to uncover the chemical basis for alcoholic fermentation in
hopes of improving the quantity and quality of beer and wine production. In 1897, the German chemist
Eduard Buchner discovered that an extract of yeast cells could be used in vitro (outside a living cell) to
convert glucose to carbon dioxide and ethanol under anaerobic conditions. The discovery that some yeast
proteins could function as chemical catalysts in the fermentation reaction ushered in the modern era of
biochemistry.
The birth of modern biochemistry can be traced to the end of the 19th century, when chemists
discovered that cell extracts of brewer’s yeast contained everything necessary for alcoholic fermentation.
That is, processes associated with living organisms could actually be understood in terms of fundamental
chemistry. The reductionist approach of breaking open cells and isolating components for in vitro chemical
reactions continued for most of the 20th century. During this time, scientists made numerous discoveries in
cellular biochemistry that transformed our understanding of the chemical basis of life. These advances
included describing the chemical structure and function of the major classes of biomolecules: nucleic acids,
proteins, carbohydrates, and lipids. Moreover, thousands of metabolic reactions that direct molecular
synthesis and degradation in cells were characterized in bacteria, yeast, plants, and animals. Knowledge
gained from these biochemical studies has been used to develop pharmaceutical drugs, medical diagnostic
tests, microbial-based industrial processes, and herbicide-resistant plant crops, among other things.
The field of biochemistry enjoyed tremendous growth in the 1970s when techniques were developed
to manipulate deoxyribonucleic acid (DNA), based on an experimental approach that became known as
recombinant DNA technology. This achievement led to the creation of the first biotechnology company in
1977, which used recombinant DNA technology to synthesize human insulin protein in yeast cells. The
following twenty years were an explosive time for biochemical research. In addition to the development of
more sophisticated biochemical tools, scientists achieved vast improvements in protein purification and
structure determination as a result of new instrumentation and computational power.
lOMoAR cPSD| 3013804
Miesfeld & McEvoy Biochemistry – DRAFT
WW Norton Publishers, New York, NY
Chapter 1 – Foundations in Biochemistry (short version)
Modern biochemistry encompasses both organic chemistry and physical chemistry, as well as areas
of microbiology, genetics, molecular cell biology, physiology, and computational biology. Six biochemical
principles provide a framework for understanding life at the molecular level:
1. The hierarchical organization of biochemical processes within cells, organisms, and ecosystems
underlies the chemical basis for life on Earth.
2. DNA is the chemical basis for heredity and encodes the structural information for RNA and
protein molecules, which mediate biochemical processes in cells.
3. The function of biomolecules is determined by their molecular structure, which is fine-tuned by
evolution though random DNA mutations and natural selection.
4. Biological processes follow the same universal laws and thermodynamic principles that govern
physical processes.
5. Life depends on water because of its distinctive chemical properties and its central role
in biochemical reactions.
6. Biological membranes are selective hydrophobic barriers that define aqueous compartments in
which biochemical reactions take place.
WHAT IS BIOCHEMISTRY?
Biochemistry aims to explain biological processes at the molecular and cellular levels. As its name implies,
biochemistry is at the interface of biology and chemistry. It is a hands-on experimental science that relies
heavily on quantitative analysis of data. Biochemists are interested in understanding the structure and
function of biological molecules. Biochemical research often involves mechanistic studies that focus on
hypothesis-driven experiments designed to answer specific biological questions. Examples include
determining how a group of proteins catalyze the synthesis of a complex biomolecule, or why biological
membranes have different physical properties depending on their chemical composition.
One of the first biochemical processes to be investigated was fermentation: the conversion of rotting
fruit or grain into solutions of alcohol through the action of yeast. The Egyptians knew as early as 2000 BC
that crushed dates produce both an intoxicating substance (ethanol) and caustic acid (acetic acid). The
Greeks used "zyme" (yeast) to produce gas (carbon dioxide) in bread and turn grapes into wine. Through
the 17th and 18th centuries, great scientific debates centered around the question of whether fermentation
was the result of an ethereal "vital life force" present in living cells, or instead, was based only on the
fundamental laws of chemistry and physics that govern the physical world. Some scientists reasoned that if
fermentation could be shown to occur outside of a living cell, then it would provide evidence that a vital life
force was not required for this chemical process.
Numerous attempts by Louis Pasteur and others to prepare cell-free extracts from yeast cells failed,
which some interpreted to mean that a vital life force was indeed required for fermentation. The turning
point came in 1897, when the German chemist Eduard Buchner (Figure 1.1A) demonstrated that carbon