Biochemistry - Bioenergetics Chapter 1

This course covers Bioenergetics (1) within Biochemistry.
The new edition is from 2024.
The course material is by Dr. Ma7moud El7efnawy.
Topics include Nucleic Acids, Proteins, Lipids, Carbohydrates, Genetic Diseases, Anemia, Sickle Cell Anemia, Athero-sclerosis, and Diabetes Mellitus.

Living cells require energy to perform work.
Types of work include mechanical (muscle contraction), electrical (nerve impulses), osmotic (absorption/secretion), and chemical (building molecules like proteins).
Sources of energy include ingested/stored food (carbohydrates, lipids, proteins) converting to energy (ATP).
Vitamins and minerals are essential for energy production but are not direct energy sources.
Hydrolysable bonds release energy when broken, specifically the pyrophosphate bond connecting two phosphate groups in ATP, releasing at least 7.3 kcal/mole of free energy.

Low-energy bonds release less than 7.3 kcal/mole of free energy upon hydrolysis.
- Examples: phosphate ester bonds (in glucose 6-phosphate), carboxyl ester bonds (connecting fatty acids to glycerol in triglycerides (TAG)), glycosidic bonds (connecting sugars in disaccharides and polysaccharides), and peptide bonds (connecting amino acids in proteins).
High-energy bonds release at least 7.3 kcal/mole of free energy upon hydrolysis.
- Examples: enol phosphate bonds (in 2-phosphoenolpyruvate (2-PEP)), carboxyl phosphate bonds (in 1,3-bisphosphoglycerate (1,3-BPG) and carbamoyl-phosphate), guanidine phosphate bonds (in creatine phosphate), and pyrophosphate bonds (in ATP).
High-energy sulfur bonds are also discussed, including thioester linkages (acyl-CoA derivatives), S-adenosyl-methionine (SAM), and others.

Metabolism involves anabolism (building up molecules) and catabolism (breaking down molecules).
Catabolism is the breakdown of large molecules for energy, while anabolism uses energy to build larger molecules (such as glycogen, proteins, and lipids).
Stages of foodstuff catabolism:
- Stage 1 (Digestion): Foodstuffs are broken down into simpler molecules (monosaccharides, fatty acids/glycerol, amino acids) without significant energy release.
- Stage 2 (Incomplete Oxidation): Simple molecules are converted into acetyl-CoA, producing reducing equivalents (NADH and FADH2), and releasing some energy.
- Stage 3 (Complete Oxidation): Acetyl-CoA is completely oxidized by the citric acid cycle (Krebs cycle), creating reduced coenzymes (NADH+H+ & FADH2), generating most energy (in the form of ATP) and releasing water and CO2.

ATP is the main energy currency of cells and is constantly being used and regenerated.
ATP is rapidly recycled via the ATP-ADP cycle to maintain its availability.
Creatine phosphate serves as a short-term energy storage form, quickly converting to ATP during muscle activity.

The AMP level acts as a sensor of the energy status of the cell.
High energy is measured as the level of ATP which activates catabolism or decreases when ADP/AMP is high
Energy is stored in the high energy phosphate bonds of molecules during breakdown reactions.
ATP and ADP is involved in the rate of catabolism reactions.
Two pathways exist for generating high-energy phosphate bonds: oxidative phosphorylation in the respiratory electron transport chain (ETC), and substrate-level phosphorylation.

High-energy bonds are created directly from substrate transfer. Examples from glycolysis are shown in detail

The ETC is a series of protein complexes in the inner mitochondrial membrane where electrons from reduced coenzymes NADH and FADH2 are transferred along the components generating ATP by oxidative phosphorylation
The components are arranged by increasing redox potential which determines the flow of spontaneous electron movement.

Proton gradient is formed across the inner mitochondrial membrane.
ATP synthase uses the proton gradient to generate ATP.
ETC activity is regulated by the levels of ADP and the electrochemical potential difference across the membrane.

The P/O ratio is the number of ATP molecules formed per atom of oxygen consumed during oxidation.
The P/O ratio for NADH and FADH2 are presented as examples
The self-regulation of ETC is determined by ADP and Electrochemical Potential

Uncouplers disrupt the proton gradient, preventing ATP synthesis, and leading to heat generation.
Examples include thermogenin, thyroid hormone, and certain drugs.
The mechanisms of uncouplers which allow the passage of protons are explained.

These examples cover thermogenesis, thyroxine, intravenous calcium, and aspirin overdose.
The mechanisms and physiological/pathological conditions are provided.

Cyanide, carbon monoxide, and hydrogen sulfide are potent inhibitors of complex IV (cytochrome c oxidase).
This prevents ATP synthesis which leads cellular dysfunction because of the absence and interference with electron transfer to the electron transport chain.

Redox reactions involve electron transfer from a donor to an acceptor.
Oxidation is the loss of electrons, and reduction is the gain of electrons. Examples of redox pairs are shown including reduced/oxidized NAD and FAD.
- Electron potential and its role in redox reactions