Biochemistry

chapter 1: introduction

Gideon J. Caballes
Internal Medicine-Rheumatology
Room 208 SUMC
objectives

■ Understand the importance of the ability of cell-free extracts of yeast to

ferment sugars, an observation that enabled discovery of the intermediates of
fermentation, glycolysis, and other metabolic pathways
■ Appreciate the scope of biochemistry and its central role in the life sciences
and that biochemistry and medicine are intimately related disciplines
■ Appreciate that biochemistry integrates knowledge of the chemical
processes in living cells with strategies to maintain health, understand
disease, identify potential therapies, and enhance our understanding of the
origins of life on earth
■ Describe how genetic approaches have been critical for elucidating many
areas of biochemistry, and how the Human Genome Project has furthered
advances in numerous aspects of biology and medicine
 Biochemistry & Medicine: Introduction
• cell = structural unit of living systems

• biochemistry
– science of the chemical basis of life (Greek “bios” = life)
– the chemical constituents of living cells and the reactions and
processes they undergo
 Biochemistry & Medicine: Introduction
• Biochemistry encompasses areas of:
– cell biology
– molecular biology
– molecular genetics
 BIOCHEMISTRY BEGAN WITH THE DISCOVERY THAT
A CELL-FREE EXTRACT OF YEAST CAN FERMENT SUGAR

• the knowledge that yeast can convert the sugars to ethyl alcohol predates
recorded history
• it was not, however, until the earliest years of the 20th century that this
process led directly to the science of biochemistry
 BIOCHEMISTRY BEGAN WITH THE DISCOVERY THAT
A CELL-FREE EXTRACT OF YEAST CAN FERMENT SUGAR

• Louis Pasteur
– despite his insightful investigations of brewing and wine making, the
great French microbiologist maintained that the process of
fermentation could only occur in intact cells
 BIOCHEMISTRY BEGAN WITH THE DISCOVERY THAT
A CELL-FREE EXTRACT OF YEAST CAN FERMENT SUGAR

• Büchner (1899): discovered that fermentation can indeed occur in cell-free

extracts
– in a crock of concentrated sugar solution, a yeast extract was added as
a preservative
– overnight, the contents of the crock fermented
• this demonstrated that fermentation can proceed in the absence of
an intact cell
• this discovery lead to a rapid and highly productive series of investigations
in the early 20th century that initiated the science of biochemistry
• These investigations revealed
– the vital role of inorganic phosphate, ADP, ATP, and NAD(H)
– the phosphorylated sugars
– the chemical reactions and enzymes (Gk “in yeast”) that convert
glucose to pyruvate (glycolysis) or to ethanol and CO2 (fermentation)
• animal models, perfused intact organs, tissue slices, cell homogenates and
their subfractions and purified enzymes all were used to isolate and
identify metabolites and enzymes

• 1930s and 1940s

– identified the intermediates of the citric acid cycle and of urea
biosynthesis
– provided insight into the essential roles of certain vitamin-derived
cofactors or “coenzymes”
• thiamin pyrophosphate
• riboflavin
• coenzyme A
• coenzyme Q
• cobamide coenzymes
• analytical ultracentrifugation, paper chromatography
• post-World War II: radioisotopes (14C, 3H and 32P) as “tracers” to identify
intermediates in pathways such as cholesterol biosynthesis, isoprenoids,
amino acid biosynthesis and catabolism

• X-ray crystallography: used to solve the 3-dimensional structure of

myoglobin and subsequently of numerous proteins, polynucleotides,
enzymes and viruses including the common cold

• Genetic advances that followed the realization that DNA was a double
helix include the polymerase chain reaction and transgenic animals or
those with gene knockouts
• 1950s
– revealed how complex carbohydrates are synthesized from and broken
down to simple sugars
– delineated the pathways for biosynthesis of pentoses and the
breakdown of amino acids and lipids
 Aim of Biochemistry: to Describe & Explain, in
Molecular Terms, All Chemical Processes of Living Cells
• major objective of biochemistry:
– complete understanding of all of the chemical processes associated
with living cells at the molecular level
• major objective of biochemistry:
– biochemists have sought to isolate numerous molecules found in cells,
determine their structures and analyze how they function
• techniques used for these purposes include the following:
 Knowledge of Biochemistry
is Essential to All Life Sciences
• biochemistry of nucleic acids lies at the heart of GENETICS
• in turn, genetics has been critical for elucidating many areas of
biochemistry
 Knowledge of Biochemistry
is Essential to All Life Sciences
• PHYSIOLOGY (the study of body function) overlaps with biochemistry
almost completely
• IMMUNOLOGY employs numerous biochemical techniques and many
immunologic approaches have found wide use by biochemists
• PHARMACOLOGY and PHARMACY rest on a sound knowledge of
biochemistry and physiology
– i.e., most drugs are metabolized by enzyme-catalyzed reactions
• TOXICOLOGY deals with poisons that act on biochemical reactions
 Knowledge of Biochemistry
is Essential to All Life Sciences
• workers in microbiology, zoology and botany employ biochemical
approaches almost exclusively and are being used increasingly to study
basic aspects of pathology (the study of disease):
– inflammation
– cell injury
– cancer

• these relationships are not surprising because life depends on biochemical

reactions and processes
• the old barriers among the life sciences are breaking down and
biochemistry is increasingly becoming their common language
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• 2 major concerns for physicians:
– understanding and maintenance of health
– effective treatment of diseases

• biochemistry impacts enormously on both of these fundamental concerns

of medicine
• biochemical studies have illuminated many aspects of health and disease,
and conversely, the study of various aspects of health and disease has
opened up new areas of biochemistry
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• the relationship between medicine and biochemistry has important
implications for the former
• as long as medical treatment is firmly grounded in the knowledge of
biochemistry and other basic sciences, practice of medicine will have a
rational basis that can be adapted to accommodate new knowledge
• this contrasts with unorthodox health cults and at least some "alternative
medicine" practices that are often founded on little more than myth and
wishful thinking and generally lack any intellectual basis
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• the interrelationship of biochemistry and medicine is a wide, two-way
street; examples are shown below:
 knowledge of the biochemical molecules (top part ) has clarified
our understanding of the diseases in medicine (bottom part)

conversely, analyses of the diseases shown below

have cast light on many areas of biochemistry
sickle cell anemia is a genetic disease and
both atherosclerosis and diabetes mellitus have genetic components
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• other examples of reciprocal benefit between biochemistry and medicine:
– knowledge of protein structure and function was necessary to
elucidate the single biochemical difference between normal
hemoglobin and sickle cell hemoglobin
– on the other hand, analysis of sickle cell hemoglobin has contributed
significantly to our understanding of the structure and function of both
normal hemoglobin and other proteins
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• another example is the pioneering work of Archibald Garrod, a physician
in England during the early 1900s
• he studied patients with a number of rare disorders (alkaptonuria,
albinism, cystinuria and pentosuria) and established that these conditions
were genetically determined
• he designated these conditions as inborn errors of metabolism
– his insights provided a major foundation for the development of the
field of human biochemical genetics
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• more recent efforts to understand the genetic basis of familial
hypercholesterolemia (which results in severe atherosclerosis at an early
age) have led to the understanding of cell receptors and of mechanisms of
uptake of cholesterol into cells
 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• studies of oncogenes in cancer cells have directed attention to the
molecular mechanisms involved in the control of normal cell growth

An oncogene is a gene that has the potential to cause cancer

 A Reciprocal Relationship Between Biochemistry &
Medicine Has Stimulated Mutual Advances
• these and many other examples emphasize how the study of disease can
open up areas of cell function for basic biochemical research
 NORMAL BIOCHEMICAL PROCESSES
ARE THE BASIS OF HEALTH
• World Health Organization (WHO) defines health as:
– a state of "complete physical, mental and social well-being and not
merely the absence of disease and infirmity"

• from a strictly biochemical viewpoint, health may be considered as:

– that situation in which all of the many thousands of intra- and
extracellular reactions that occur in the body are proceeding at rates
commensurate with the organism's maximal survival in the physiologic
state
– overall, caring for patients requires not only biologic principles but also
of psychologic and social principles

infirmity: physical weakness, lack of strength, ailment

 Biochemical Research Has Impact on
Nutrition & Preventive Medicine
• one major prerequisite for the maintenance of health is optimal dietary
intake of a number of chemicals; these are:
– vitamins
– amino acids
– fatty acids
– minerals
– water

• both biochemistry and nutrition are concerned with the study of various
aspects of these chemicals-- there is a close relationship between these
two sciences
 Biochemical Research Has Impact on
Nutrition & Preventive Medicine
• more emphasis placed on systematic attempts to maintain health and forestall
disease (preventive medicine)
– i.e., nutritional approaches to the prevention of atherosclerosis and cancer
• understanding nutrition depends to a great extent on knowledge of
biochemistry

atherosclerosis = a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls
 Most Diseases Have a Biochemical Basis

• Apart from infectious organisms and environmental pollutants, many

diseases are manifestations of abnormalities in genes, proteins, chemical
reactions, or biochemical processes, each of which can adversely affect
one or more critical biochemical functions. Examples of disturbances in
human biochemistry responsible for diseases or other debilitating
conditions include electrolyte imbalance, defective nutrient ingestion or
absorption, hormonal imbalances, toxic chemicals or biologic agents, and
DNA-based genetic disorders.
• To address these challenges, biochemical research continues to be
interwoven with studies in disciplines such as genetics, cell biology,
immunology, nutrition, pathology, and pharmacology.
• In addition, many biochemists are vitally interested in contributing to
solutions to key issues such as the ultimate survival of mankind, and
educating the public to support use of the scientific method in solving
environmental and other major problems that confront us
• most if not all diseases are manifestations of abnormalities of molecules,
chemical reactions, or biochemical processes
• all of them affect one or more chemical reactions or molecules
• in most of these conditions, biochemical studies contribute to both the diagnosis
and treatment
 impact of the Human Genome Project (HGP)
on biochemistry, biology, & medicine
• late 1990s: sequencing of the human genome started by the HGP
• July 2000: over 90% of the human genome had been sequenced
• 2003: with the exception of a few gaps, the sequence of the entire human
genome was completed (50 years after Watson and Crick described the
double-helical nature of DNA)

• implications of the HGP for biochemistry, biology, medicine and related

health sciences are tremendous
• it is now possible to isolate any gene and determine its structure and
function
• many previously unknown genes have been revealed
• new light has been thrown on human evolution
• procedures for tracking disease genes have been greatly refined

HGP = human genome project

Human Genome Project (HGP)
• Major advances in biochemistry and understanding human health and
disease continue to be made by mutation of the genomes of model
organisms such as yeast and of eukaryotes such as the fruit fly Drosophila
melanogaster and the round worm Caenorhabditis elegans. Each organism
has a short generation time and can be genetically manipulated to provide
insight into the functions of individual genes.
• These advances can potentially be translated into approaches that help
humans by providing clues to curing human diseases such as cancer and
Alzheimer disease
areas of current interest that have developed as a result of
the progress made in the HGP

HGP = human genome project

• Bioengineering: application of engineering to biology and medicine

• Bioethics: area of ethics concerned with the application of moral and ethical
principles to biology and medicine

• Bioinformatics: discipline concerned with the collection, storage and analysis

of biologic data, mainly DNA and protein sequences

• Biophysics: application of physics and its technics to biology and medicine

• Biotechnology: the field in which biochemical, engineering and other

approaches are combined to develop biological products of use in medicine
and industry

• Gene Therapy: applies to the use of genetically engineered genes to treat

various diseases
 • genome = the complete set of genes of an organism (eg, human genome)
• Genomics = the in-depth study of the structures and functions of genomes

Graphical representation of the

idealized human diploid karyotype
showing the organization of the
genome into chromosomes.
• glycome = the total complement of simple and complex carbohydrates in an
organism; the entirety of carbohydrates in a cell
• Glycomics = study of the structures and functions of glycomes
• proteome
– the entire set of proteins expressed by a genome, cell, tissue or organism at a
certain time (the complete complement of proteins of an organism)
• Proteomics = study of the structures and functions of proteomes, including
variations in health and disease
• transcriptome = the complete set of RNA transcripts produced by the
genome at a fixed period in time
• Transcriptomics: = study of gene expression at the RNA level
 • lipidome = the complete complement of lipids found in an organism; or the
totality of lipids in a cell
• Lipidomics = study of the structures and functions of all members of the
lipidome and their interactions in health and disease

The lipodome in connection with

the total interactome of a cell.
interactome is the whole set of molecular interactions in a particular cell
• metabolome = the complete complement of metabolites (metabolic
intermediates, hormones, signaling molecules and secondary metabolites
involved in metabolism)
• Metabolomics = study of the structures, functions and changes of
metabolomes in various metabolic states
• Molecular Diagnostics: the use of molecular approaches (eg, DNA probes) to
assist in the diagnosis of biochemical, genetic, immunologic, microbiologic
and other medical conditions
• stem cell is an undifferentiated cell that has the potential to renew itself and
to differentiate into any of the adult cells found in the organism
• Stem cell biology deals with the biology of stem cells and their uses in various
diseases
• Nutrigenomics: study of the effects of nutrients on genetic expression and of
the effects of genetic variations on the handling of nutrients

• Pharmacogenomics: use of genomic information and technologies to

optimize the discovery and development of drugs and drug targets

• Synthetic Biology: combines biomolecular technics with engineering

approaches to build new biological functions and systems

• Systems Biology: field of science in which complex biologic systems are

studied as integrated wholes (as opposed to the reductionist approach of
classic biochemistry)
• many so-called-omics fields have sprung up, involving comprehensive
studies of the structures and functions of the molecules with which each is
concerned
• the products of genes (RNA molecules and proteins) are being studied
using the technics of transcriptomics and proteomics
• one spectacular example of the speed of progress in transcriptomics is the
explosion of knowledge about small RNA molecules as regulators of gene
activity
• other -omics fields include glycomics, lipidomics, metabolomics,
nutrigenomics, and pharmacogenomics
• to keep pace with the amount of information being generated,
bioinformatics has received much attention
• other related fields to which the impetus from the HGP has carried over
are biotechnology, bioengineering, biophysics, and bioethics.
• Stem cell biology is at the center of much current research.
• Gene therapy has yet to deliver the promise that it contains, but it seems
probable that will occur sooner or later.
• Many new molecular diagnostic tests have developed in areas such as
genetic, microbiologic, and immunologic testing and diagnosis systems
biology is also burgeoning synthetic biology is perhaps the most intriguing
of all.
• This has the potential for creating living organisms (eg, initially small
bacteria) from genetic material in vitro.
• These could perhaps be designed to carry out specific tasks (eg, to mop up
petroleum spills).
• As in the case of stem cells, this area will attract much attention from
bioethicists and others
• all of the above have made the present time a very exciting one for
studying or to be directly involved in biology and medicine.
• The outcomes of research in the various areas mentioned above will
impact tremendously on the future of biology, medicine and the health
sciences
 SUMMARY

• Biochemistry
– science concerned with studying various molecules that occur in living
cells and organisms and with their chemical reactions
– is concerned with the entire spectrum of life forms, from relatively
simple viruses and bacteria to complex human beings
– life depends on biochemical reactions, thus biochemistry has become
the basic language of all biologic sciences

• results of the HGP and of research in related areas will have a profound
influence on the future of biology, medicine and other health sciences

HGP = human genome project

 SUMMARY

• Biochemistry and Medicine are intimately related

– advances in biochemical knowledge have illuminated many areas of
medicine while medicine (the study of diseases) has often revealed
previously unsuspected aspects of biochemistry
– use of various biochemical laboratory tests is an integral component of
diagnosis and monitoring of treatment
– health depends on a harmonious balance of biochemical reactions in
the body
– disease reflects abnormalities in biomolecules, biochemical reactions
or biochemical processes
• A sound knowledge of biochemistry and of other related basic disciplines
is essential for the rational practice of medicine and related health
sciences