Biochemistry of Disease

All Diseases Have a Biochemical Basis:

-Life as we know it on earth depends upon biochemical reactions.

-If they cease, death results.

-Health: is defined as "the harmonious functioning of thousands of biochemical reactions and processes that occur in normal cells and that operate to maintain homeostasis (constancy) of the internal environment".

-Disease: results from perturbations of structures, i.e. DNA in genetic diseases amounts, of certain biomolecules perturbations, of important biochemical reactions and processes.

Six Points Regarding Disease From a Biochemical Standpoint:

[1] Many diseases are determined genetically.

[2] All classes of biomolecules found in cells are affected in structure, function or amount in one disease or another. Biomolecules can be effected in a primary or secondary manner.

Involvements of Various Biomolecules in Disease:

Biomolecule Property Affected Disease Fundamental Cause
DNA Structure Sickle Cell Anemia Mutation
RNA Structure Thalassemia Mutation (faulty splicing mRNA)
Protein Structure / Function Sickle Cell Anemia Mutation
Lipid Amount Tay-Sachs Mutation
Polysaccharide Amount Glycogen Storage Mutation (gene for Glycogen Phosphorylase)
Electrolyte Amount in Sweat Cystic Fibrosis Mutation (membrane protein affecting transport of Cl-)
Water Amount Cholera Infection (bacterial, small intestine)


[3] Biochemical perturbations that cause disease may occur rapidly or slowly.

[4] Diseases can be caused by deficiency or excess of certain biomolecules.

[5] Almost every cell organelle has been involved in the genesis of various diseases.

Involvements of the Major Intracellular Organelles in Various Diseases:

Organelle Disease(s) Mechanism

Organelle Disease(s) Mechanism
Nucleus Most genetic diseases Mutations in DNA
Mitochondria Hereditary myopathies Mutations in DNA affecting the structure of proteins (i.e. NADH DH)
ER Chemical toxicities Enzymes like Cytochrome P-450 can activate various compounds to potentially toxic species
Golgi I-cell disease Absence of a phosphotransferase resulting in lysosomal enzymes being misdirected and secreted by affected cells
Plasma Membrane Metastasis of cancer cells Changes in the oligosaccharides of glycoproteins
Lysosome Lysosomal storage disease Decreased activity (due to mutations) of various hydrolases result in accumulation of certain biomolecules


[6] Different biochemical mechanisms can produce similar pathologic, clinical and laboratory findings.

The Major Pathologic Processes by Which the Body Reacts to Disease-Causing Perturbations:

Pathologic Process One Cause Disease Biomolecule(s) Involved
Inflammation, acute or chronic Infection, bacterial or viral Pneumonia PG's and LT's
Degeneration Various Chemicals Fatty Liver Ethanol
Organ Enlargement Accumulation of certain compounds Gaucher's Disease (enlarged liver and spleen) Glucosylceramide
Anemia Lack of Vitamin Iron Deficiency Anemia Iron
Neoplasia Irradiation Leukemia DNA Damage
Cell Death Diminished blood supply MI Lack of Oxygen
Fibrosis Follows cell death Cirrhosis of the Liver Accumulation of Collagen
Calculus High local concemtrations of certain compounds Gout Uric Acid


Genetic Diseases:

-The molecular basis of most genetic diseases will be revealed within the next decade.

-Genetic diseases account for about 10% of hospitalized children and many of the chronic diseases that afflict adults (i.e. diabetes, atherosclerosis).

-The successful sequencing of the human genome has major implications for the study of health and disease.

Successful treatment for Some Genetic Diseases:

Three Strategies:

(1) Administration of the missing product or limiting the availability of substrate.

(2) Replacement of an absent enzyme or protein.

(3) Removal of excess of a stored compound.

(4) Direct attempts to correct the basic genetic abnormality.

Principle Disease Treatment
Replace Product Goiter Administration of 1-Thyroxine
Limit Substrate PKU Diet low in Phe
Replace Enzyme Gaucher's Injections of b-glucosidase
Replace Protein Hemophilia Injections of Factor VIII
Supply Co-Factor Aciduria Injections of Vitamin B-12
Replace Organ Galactosemia Liver Transplantation
Gene Therapy Many Adenosine Deaminase Deficiency


Dr. Noel Sturm 2015