BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 16. ENERGY METABOLISM

16.3. The Final Stage of Catabolism — The Main Source of Hydrogen Donors for the ETC

16.3.2. Hypoenergetic States

All living cells constantly require ATP to support various vital functions. Brain cells consume large amounts of ATP for neurotransmitter synthesis, nerve cell regeneration, maintaining the necessary Na⁺ and K⁺ gradient, and conducting nerve impulses; kidneys use ATP during the reabsorption of various substances in urine formation; the liver carries out

the synthesis of Glycogen, fats, Proteins, and many Other Compounds; the myocardium continuously performs the mechanical work required for Blood Circulation; skeletal Muscles consume negligible amounts of ATP at rest, but during physical exertion, these demands increase tenfold (Table 16.5). At the same time, Cells maintain virtually no reserve stores of ATP. For example, if ATP Synthesis in the myocardium stops, its reserves are depleted within seconds.

Class="center">Table 16.5

Rates of O₂ and ATP Consumption in Various Tissues

As is well known, for the continuous synthesis of ATP, cells require a supply of metabolites to act as respiratory substrates, as well as oxygen as the terminal electron acceptor in oxidation reactions coupled with ATP synthesis. The disruption of any metabolic step that leads to a cessation of ATP synthesis is detrimental to The Cell.

States characterized by decreased ATP synthesis are collectively referred to as "Hypoenergetic States." Causes of such conditions may include starvation, vitamin B₁, PP, and B₂ deficiencies, and Hypoxia. Hypoxia can occur due to an insufficient oxygen content in inhaled air; pulmonary diseases and impaired pulmonary ventilation; or Circulatory Disorders caused by heart disease, vascular spasms, thrombosis, or blood loss. Furthermore, hypoxia can be triggered by inherited or acquired abnormalities in Hemoglobin Structure. Hypoenergetic states are also frequently caused by impaired oxygen utilization within cells. These impairments may stem from:

✵ the action of inhibitors and uncouplers in the ETC;

✵ iron-deficiency anemias;

✵ reduced levels of hemoglobin and other iron-containing proteins (Cytochromes, Fe-S proteins), which impair Electron Transport and ATP synthesis;

✵ hereditary defects in ETC and Citric Acid Cycle Enzymes.

Approximately 13 of the nearly 100 proteins involved in Oxidative Phosphorylation are encoded by Mitochondrial DNA: 7 subunits of complex I, a subunit of complex III, 3 subunits of complex IV, and 2 subunits of complex V, along with the Translation components necessary for them. Other mitochondrial proteins are synthesized in The Nucleus.

Nuclear DNA encodes over 80 protein subunits involved in oxidative phosphorylation. Impairments in oxidative phosphorylation are primarily associated with Mutations in mitochondrial DNA, which occur approximately 10 times more frequently than in nuclear DNA. Tissues with high ATP demands (Central Nervous system, skeletal muscles, myocardium, kidneys, and liver) are the most sensitive to disruptions in oxidative phosphorylation.