BIOCHEMISTRY: A TEXTBOOK FOR MEDICAL UNIVERSITIES - E. S. Severin - 2004

SECTION 1. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

VIII. Alterations in the Protein Composition of the Body

The protein composition of a healthy adult body is relatively constant, although variations in the amounts of specific Proteins in Organs and Tissues can occur depending on diet and nutritional patterns, a person's physiological activity, and biological rhythms.

A. Changes in the protein composition of Cells during differentiation

During The Development of a multicellular Organism, particularly at the stages of Cell Differentiation, the protein composition changes significantly. Each type of specialized cell is characterized by the appearance of specific proteins that determine its unique biological Functions. For instance, erythrocytes alone contain Hemoglobin, which transports oxygen to tissues, whereas retinal cells contain the protein rhodopsin, essential for capturing light photons. In addition, specialized cells differ in the amounts of proteins that are present in virtually all or many Cells of the body.

Various diseases are accompanied by changes in the protein composition of tissues. These alterations are referred to as proteinopathies, which are classified into hereditary and acquired types.

B. Hereditary proteinopathies

Hereditary proteinopathies develop As a result of defects in the GENETIC APPARATUS OF an individual. A particular protein may either fail to synthesize altogether or be synthesized with an altered Primary Structure. Examples of hereditary proteinopathies include the hemoglobinopathies discussed above. Depending on The Role of the defective protein in the body's vital activity, the extent of conformation and functional impairment, and the individual's homo- or heterozygosity for that protein, hereditary proteinopathies can cause disorders of varying severity, ranging from fatal outcomes before birth or in the first months of life.

C. Acquired proteinopathies

Any disease is accompanied by an alteration in the body's protein composition; in other words, an acquired proteinopathy develops. In these cases, the Introduction/19.html">Primary structure of the proteins remains intact, but quantitative changes typically occur, especially in the organs and tissues undergoing pathological processes. For example, in pancreatitis, The production of Enzymes required for the Digestion of nutrients in the gastrointestinal tract is reduced.

In some instances, acquired proteinopathies develop as a result of changes in the environmental conditions under which proteins function. For instance, a shift in pH toward the alkaline side (alkalosis of various origins) alters the conformation of hemoglobin, increasing its affinity for O₂ and diminishing O₂ delivery to tissues (tissue Hypoxia).

Sometimes, disease leads to an elevated level of metabolites in cells and Blood serum, resulting in the modification of certain proteins and impaired function. For example, elevated blood glucose concentrations in Diabetes Mellitus lead to its non-enzymatic attachment to proteins (protein

glycation). An example is the increased level of glycated hemoglobin in erythrocytes, which enhances its affinity for O₂ and impairs O₂ transport to tissues. Glycation of the lens Proteins of the eye (crystallins) leads to its opacity and the development of cataracts.

Furthermore, proteins that are normally detected only in trace amounts can leak into the blood from damaged organs. In various diseases, biochemical analyses of blood protein composition are frequently used to refine a clinical Diagnosis. For example, in pancreatitis, the blood shows an elevated activity of pancreatic amylase (an enzyme involved in starch breakdown), which normally should not enter the bloodstream but is instead secreted through the pancreatic duct into the duodenum during digestion (see Section 2).

In some cases, biochemical data on changes in the protein composition of blood or urine can be pivotal in establishing a diagnosis. For example, in multiple myeloma (a malignant transformation of plasma cells that synthesize IMMUNOGLOBULINS), Bence-Jones proteins appear in the blood and urine, though they are present in low concentrations in healthy individuals as well. These proteins represent the light chains of immunoglobulin G, the synthesis of which is upregulated in malignant cells.