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:
 Many diseases are determined genetically.
 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|
|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)|
 Biochemical perturbations that cause disease may occur rapidly or slowly.
 Diseases can be caused by deficiency or excess of certain biomolecules.
 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
 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|
|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|
-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:
(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.
|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