Relationship between biochemistry and medicine

Biochemistry and medicine

Introduction

Biochemistry is the science concerned with the various
molecules that occur in living cells and organisms and with their chemical
reactions. Anything more than a superficial comprehension of life-in all
diverse manifestations-demands a knowledge of biochemistry. Medical students
who acquire a sound knowledge of biochemistry will be in a strong position to
deal with two central concerns of the health sciences: (1) the understanding
and maintenance of health and (2) the understanding and effective treatment of
disease.

Biochemistry is the chemistry of life

Biochemistry can be defined more formally as the science
concerned with the chemical basis of life (Gk bios “life”).

The cell is the structural unit of living systems.
Consideration of this concept leads to a functional definition of biochemistry
as the science concerned with  the
reactions and processes that they undergo. By this definition, biochemistry
encompasses large areas of cell biology, and of molecular genetics.

The aim of biochemistry is to describe and explain, in molecular terms, all
chemical processes of living cells.

The major objective of biochemistry is the complete
understanding at the molecular level of all the chemical processes associated
with living cells. To achieve this objective, biochemists have sought to
isolate the numerous molecules found in cells determine their structures, and
analyze how they function. To give one example, the efforts of many biochemists
to understand the molecular basis of contractility-a process associated
primarily, but not exclusively, with muscle cells-have entailed purification of
many molecules, both simple and complex, followed by detailed
structure-function studies. Through these efforts, some of the features of the
molecular basis of muscle contraction have been revealed.

A further objective of biochemistry is to attempt to
understand how life began, knowledge of this fascinating subject is still
embryonic.

A scope of biochemistry is as wide as life itself. Wherever
there is life, chemical processes are occurring. Biochemists study the chemical
processes are occurring. Biochemists study the chemical processes that occur in
micro organisms, plants, insects, fish, birds, mammals, and human beings.
Students in the bio-medical sciences will be particularly interested in the
biochemistry of less complex forms of life is often of direct relevance to
human biochemistry. For instance, 
contemporary theories of the regulation 
of the activities of genes and of the enzymes in human emanate from
pioneering studies on bread molds and on bacteria. The field of recombinant DNA
emerged from studies on bacteria and their viruses; their rapid multiplication
times and the ease of extracting their genetic material make them suitable for
genetic analyses and manipulations, knowledge gained from the study of viral
genes responsible for certain types of cancer in animals (viral oncogenes) has
provided profound insights into how human cells become cancerous.

The Knowledge of biochemistry is essential to all life sciences.

The biochemistry of the nucleic acids lies at the heart of
genetics; in turn, the use of genetic approaches has been critical for
elucidating many areas of biochemistry. 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; in particular, 
most drugs are metabolized by enzyme-catalyzed reactions, and the
complex interactions among drugs are best understood biochemically. Poisons act
on biochemical reactions or processes; this is the subject matter of
toxicology. Biochemical approaches are being used increasingly to study basic
aspects of pathology (the study of disease), such as inflammation, cell injury,
and cancer. Many workers in microbiology, zoology and botany employ biochemical
approaches almost exclusively. This relationships are not surprising, because
life as we know; depends on biochemical reactions and processes, in fact, the
old barriers among the life sciences are breaking down, and biochemistry is
increasingly becoming their common language.

A reciprocal relationship between biochemistry and medicine has stimulated
mutual advances.

As stated earlier, the two major concerns for workers in the
health sciences-and particularly physicians-are the understanding and
maintenance of health and the understanding and effective treatment of diseases.
Biochemistry impacts enormously on both of these fundamental concerns of
medicine. In fact, the inter relationship of biochemistry and medicine is a
wide, two-way street. 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 and medicine. For instance, a
knowledge of protein structure and function was necessary to elucidate  the single biochemical difference between
normal and sickle cell haemoglobin. On the other hand, analyses of sickle cell
haemoglobin has contributed significantly to our understanding of the structure
and function of both normal haemoglobin and other proteins. Another example is
the pioneering work of Garrod, a physician in England during the early years of
the 20th century. He studied patients with a number of  relatively rare disorders (alkaptonuria,
albinism, cystinuria, and pentosuria; and conditions were genetically
determined. Garrod designated these conditions as inborn errors of metabolism,
his insights provided a major foundation for the development of the field of
human biochemical genetics.

This relationship between medicine and biochemistry has
important philosophical implications for the former. As long as medical
treatment is firmly grounded in a knowledge of biochemistry and other relevant
basic sciences (eg physiology, microbiology, nutrition), the practice of
medicine will have a rational basis that can be adapted to accommodate new
knowledge. This contrasts with orthodox health cults, which are often founded
on little more than myth and wishful thinking and generally lack any
intellectual basis.

Normal biochemical processes are the basis of health.

The 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 view point, health
may be considered that situation in which all of the many thousands of intra-
and extr-cellular reactions that occur in the body are proceeding at rates
commensurate with its maximal survival in the physiological state. However,
this is an extremely reduvtionist view, and it should be apparent that caring
for the health of patients requires not only a wide knowledge of biologic
principles but also of psychologic and social principles.

Biochemical research has impact on nutrition and preventive medicine.

One major prerequisite for the maintenance of health is that
there be optimal dietary intake of a number of chemicals; the chief of these
are vitamins, certain amino acids, various minerals, and water. Because much of
the subject matter of both biochemistry and nutrition is concerned with the
study of various aspects of these chemicals, there is a close relationship
between these two sciences. Moreover, as attempts to curb the rising costs of
medical care, more emphasis is being placed on systematic attempts to maintain
health and forestall disease, i.e, on preventive medicine. Thus, nutritional
approaches to-for example-the prevention of atherosclerosis and cancers are
receiving increased emphasis. Understanding nutrition depends to a great extent
on the knowledge of biochemistry.

All disease has a biochemical basis.

All diseases are manifestations  of abnormalities of molecules, chemical
reactions or processes. The major factors responsible for causing disease in
animals are state below; all of them affect one or more critical chemical
reactions or molecules in the body. The majority  of diseases discussed in this text are due to
causes 5,7 and 8.

1.      
Physical agents: mechanical trauma, extremes of
temperature, sudden changes in atmospheric pressure, radiation, electric shock.

2.      
Chemical agents including drugs: certain toxic
compounds, therapeutic drugs, etc.

3.      
Biological agents: viruses, bacteria, fungi,
higher forms of parasites.

4.      
Oxygen lack: loss of blood supply, depletion of
the oxygen-carrying capacity of the blood, poisoning of the oxidative enzymes.

5.      
Genetic disorders: congenital, molecular.

6.      
Immunologic reactions: anaphylaxis, autoimmune
disea.

7.      
Nutritional imbalances: deficiencies, excesses.

8.      
Endocrine imbalances: hormonal deficiencies,
excesses.

Biochemical studies contribute to diagnosis, prognosis and treatment.

There is a wealth of documentation  of the use of biochemistry in prevention,
diagnosis, and treatment of disease; many examples will be cited throughout
this text. Here, seven brief examples are given to illustrate the breadth of
the subject and stimulate the reader’s interest. Further information on disease
and their causes are listed in the below table.

Disease	causes
Scurvy  (MIM 240400), rickets	Deficiencies of vitamin C and D, respectively
Kwashiorkor	Deficiency of dietary protein
Atherosclerosis	Genetic, dietary, and environmental factors
Phenylketonuria (MIM 261600)	Mutations in the gene encoding phenylalanine hydroxylase
Cystic fibrosis (MIM 219700)	Mutations in the gene encoding the CFTR protein
Cholera	Exotoxin of vibrio cholera
Dibetes mellitus, type 1 (MIM 222100)	Genetic and environmental factors resulting in the deficiency of insulin.

 Note: the numbers in parenthesis are the mendelian inheritance in man numbers (see
references); where no number is listed, the condition is not listed in that
work, probably because it is not predominantly a genetic condition (eg,
rickets, kwashiorkor, cholera) or because it is a pathologic process (eg,
atherosclerosis) as opposed to a distinct disease entity.

1.      
Humans must ingest a number of complex or organic
molecules called vitamins in order to maintain health. If a particular vitamin
is deficient in the diet, the reactions in which it is involved are
compromised. This situation may be manifested as a deficiency disease such as
scurvy or rickets (due to lack of intake of vitamin C and D, respectively). The
elucidation of the roles played by  the
vitamins or their biologically active derivatives in animal and human cells has
been a concern of biochemists and nutritionists since the turn of the 20th
century. Once a disease was established as resulting from a vitamin deficiency,
it became rational to treat it by administration of the appropriate vitamin.

2.      
The fact that many plants in Africa are
deficient in one or more essential amino acids (ie, amino acids that must be
supplied in the diet in order to maintain health) helps explain the
debilitating malnutrition (kwashiorkor) suffered by infants who depend on such
plants as major dietary sources of protein. Treatment of deficiencies of
essential  amino acids is rational but,
unfortunately,  not always feasible.  It consist of providing a well balanced  diet containing adequate amounts of all the
essential amino acids.

3.      
Greenland Inuit consume consume large  quantities of fish oils rich in certain
poly-unsaturated fatty acids and are known to have low plasma levels of
cholesterol and a low incidence of atherosclerosis. These observations have
stimulated interest in the use of poly-unsaturated fatty acids to reduce plasma
levels of cholesterol.

The vitamin deficiency diseases are
examples of nutritional imbalances. Atherosclerosis may be considered as a
nutritional imbalance, but other important factors (eg, genetic) are also
involved.

4.      
The condition known as phenylketonuria, if
untreated, may lead to severe mental retardation in infancy. The biochemical
basis of phenylketonuria has been known since 1953; the disorder is genetically
determined and results from low or absent activity of the enzyme that converts
the amino acid phenylalanine to the amino acid tyrosine. This in turn causes an
elevation of the level of phenylalanine in the blood, resulting in damage to the
developing central nervous system. When the nature of the biochemical lesion in
phenylketonuria was revealed, it became rational to treat the disease by
placing affected infants on a diet low in phenylalanine. Once biochemical
screening tests for diagnosing phenylketonuria at birth became available,
effective treatment could start immediately.

5.      
Cystic fibrosis is a common genetic disease
affecting the exocrine glands. It is characterized by abnormally viscous
secretions that plug up the secretory ducts of the pancreas and the
bronchoiles. In addition, patients with cystic fibrosis exhibit elevated amount
of chloride in their sweat. Victims often die at their early age from lung
infections. The isolation and complete sequence of the gene responsible for
this disease was reported in 1989. The normal gene code for a transmembrane
protein (the  cystic fibrosis
transmembrane conductance regulator), 1480 amino acids in length, which
functions as a chloride channel. The abnormality in approximately 70% of
patients with cystic fibrosis is a deletion of three bases in the gene,
resulting in the transmembrane protein lacking amino acid number 508, a
phenylalanine residue. How this deletion impares the function of the
transmembrane protein and results in the excessively thick mucus is being
determined. This important work should facilitate the detection of carriers of the
cystic fibrosis gene and, it is hoped, lead to more rational treatment of the
disease than exists at present. For instance, it may be possible to design
drugs that can correct the abnormality in the transmembrane protein;  like wise, it may be possible to introduce
the normal gene into lung cells by gene therapy. Phenylketonuria and cystic
fibrosis are examples of genetic diseases.

6.      
Analysis of the mechanism of action of the
bacterial toxin that causes cholera has provided important insights into how
the clinical manifestations of this disease (copious diarrhea and loss of salt
and water) are brought about.

7.      
Diabetes mellitus is prevalent in many parts of
the world. One fundamental aspect of diabetes is an abnormality of the
metabolism of glucose, resulting in elevated blood levels (hyperglycemia). Two
major types are recognized: type 1 (insulin-dependent) and type 2
(non-insulin-dependent). To understand diabetes mellitus and treat it
effectively, one must be familiar with the metabolism of glucose and the many
effects of insulin in the human body.

Many biochemical studies illuminate disease mechanisms, and diseases
inspire biochemical research.

The initial observations made by Garrod on a small group of
inborn errors of metabolism in the early 1900s stimulated the investigation of
the biochemical pathways affected in this conditions. Efforts to understand the
basis of the genetic disease known as familial hypercholesterolemia, which
results in severe atherosclerosis at an early age, have led to dramatic progress
in knowledge of cell receptors and of mechanisms of uptake of cholesterol into
cells. The ongoing studies of oncogenes in cancer cells have directed attention
to the molecular mechanisms involved in the control of normal cell growth.
These and many other possible examples illustrate how the study of disease can
open up whole areas of cell function for basic biochemical research.

This text will help relate biochemical knowledge to clinical problems

Some major uses of biochemical investigations and laboratory
tests in relation to diseases are summarized in the table below.

USE	EXAMPLE
1.       To review the fundamental causes and mechanisms of diseases	Demonstration of the nature of genetic defects in cystic fibrosis.
2.       To suggest rational treatments of diseases based on (1) above	Use of diet low in phenylalanine for treatment of phenylketonuria.
3.       To assist in diagnosis of specific diseases	Use of plasma enzyme creatine kinase MB (CK-MB) in the diagnosis of myocardial infarction.
4.       To act as screening tests for the early diagnosis of certain disease	Use of measurement of blood thyroxine or thyroid-stimulating hormone (TSH) in the neonatal diagnosis of congenital hypothyroidism.
5.       To assist in monitoring the progress (eg, recovery, worsening, remission, or relapse) of certain diseases	Use of the plasma enzyme alanine aminotransferase (ALT) in monitoring the progress of infectious hepatitis.
6.       To assist in assessing the response of diseases on therapy	Use of measurement of blood carcinoembryonic antigen (CEA) in certain patients who have been treated for cancer of the colon.

SUMMARY

Biochemistry is the science concerned with studying the
various molecules that occur in living cells and organisms and with their
chemical reactions. Because life depends on biochemical reactions, biochemistry
has become the basic language of all biologic sciences.

Biochemistry is concerned with the entire spectrum of life
forms, from simple viruses and bacteria to complex human beings.

Biochemistry and medicine are intimately related. Health
depends on harmonious balance of biochemical reactions occurring in the body,
and disease reflects abnormalities in biomolecules, biochemical reactions, or
biochemical processes.

Advances in biochemical knowledge have illuminated many
areas of medicine. Conversely, the study of diseases has often revealed
previously unsuspected aspects of biochemistry.

Biochemical approaches are often fundamental illuminating
the causes of disease and in designing the therapies.

The judicious use of various biochemical laboratory tests is
an integral component of diagnosis and monitoring of treatment.

A sound knowledge of biochemistry and of other related basic
disciplines is essential for the rational practice of medical and related
health sciences.

REFERENCES

Garrod AE: inborn errors of metabolism. (Croonian lectures.)
Lancet 1908;2:1, 73, 142, 214.

Kornberg A: Basic Rechearch: The lifeline of medicine.  FASEB J 1992;6:3143.

Kornberg A: Centenary of the birth of modern biochemistry.
FASEB J 1997;11:1209.

McKusick VA: Mendelian inheriatance in man. Catalogs of
human Genes and genetic diosorders, 12th ed. Johns Hopkins Press,
1998. [abbreviated MIM]

Online mendelian inheriatance in man (OMIM): center for
medical genetics, Johns Hopkins university and national biotechnology
information, national library of medicine, 1997.

ADAPTED FROM HARPER’S BIOCHEMISTRY, REFER TO YOUR TEXTBOOK
FOR DETAILED INFORMATION