Metabolism Overview and Pathways

Metabolism Overview

• Metabolism is the sum of all chemical reactions in a living cell.
• It involves catabolism (breaking down molecules to release energy) and anabolism (building complex molecules).
• These reactions are catalyzed by enzymes.
• It is essential for health, growth, reproduction, and survival.

Metabolic Roadmap

• Metabolic pathways are series of interconnected biochemical reactions converting a substrate molecule into a final product.
• Pathways are categorized as anabolic or catabolic.
  • Anabolic: Assembling small molecules into large ones, requiring energy.
  • Catabolic: Breaking down large molecules into smaller ones, releasing energy.

Metabolism and Cell Structure

• Metabolism is tightly linked to cell structure
• Metabolic pathways are organized into compartments providing specific conditions.
• These reactions can be classified into catabolism (breaking down molecules) and anabolism (building complex molecules).

Important Compounds

• Adenosine phosphates (ATP, ADP, AMP): Key metabolic components involved in energy transfer in cells.
  • AMP is a structural part of RNA.
• Flavin Adenine Dinucleotide (FAD): A coenzyme involved in numerous metabolic redox reactions.
• Nicotinamide Adenine Dinucleotide (NAD): Important coenzyme in cellular reactions, often serving as an oxidizing agent.

Mitochondria

• Mitochondria are the powerhouses of the cell.
• They are primary sites for aerobic respiration.
• They perform the citric acid cycle, oxidative phosphorylation, and fatty acid oxidation generating ATP.

Other Cellular Structures

• Endoplasmic Reticulum (ER): Involved in detoxification and calcium storage, along with protein and steroid synthesis.
• Lysosomes and Peroxisomes: Degrade macromolecules and detoxify reactive oxygen species.
• Plasma Membrane: Transports molecules, including proteins and signaling molecules.

Important Carboxylate Ions in Metabolic Pathways

• Pyruvate (C₃H₃O₃^-): An end product of glycolysis, a crucial intersection of metabolic pathways.
• Oxaloacetate (C₄H₄O₅^2-): A key intermediate in the citric acid cycle and gluconeogenesis.
• Citrate (C₆H₅O₇^3-): The initial intermediate in the citric acid cycle.
• α-Ketoglutarate (C₅H₄O₅^2-): Involved in the citric acid cycle and amino acid metabolism.
• Malate (C₄H₄O₅^2-): An intermediate in the citric acid cycle.
• Succinate (C₄H₄O₄^2-): A citric acid cycle intermediate involved in the electron transport chain.
• Fumarate (C₄H₂O₄^2-): An intermediate in both the citric acid and urea cycles.

High-Energy Phosphate Compounds

• ATP (adenosine triphosphate) contains high-energy bonds between phosphates, acting as a significant energy carrier in the cell.

Four Stages of Biochemical Energy

• Stage 1 (Digestion): Breaking down complex nutrients (carbohydrates, fats, and proteins) into smaller, usable components like simple sugars, fatty acids, and amino acids.
• Stage 2 (Acetyl Group Formation): Oxidizing the simple molecules to form Acetyl-CoA, a crucial starting material for the next stage.
• Stage 3 (Citric Acid Cycle): Oxidizing Acetyl-CoA to CO₂ and producing high-energy electron carriers (NADH, FADH₂) and some ATP.
• Stage 4 (Oxidative Phosphorylation): Transferring electrons from NADH and FADH₂ through an electron transport chain to produce significantly more ATP from the electrochemical gradient.

Control of Citric Acid Cycle

• Several points in the citric acid cycle are regulated—the three key enzymes mentioned (citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) are also important points of control.
• ATP and NADH act as inhibitors while ADP and NAD+ act as activators.

Electron Transport Chain

• The electron transport chain (ETC) is the process of reoxidizing the high-energy electron carriers (NADH and FADH2) to produce ATP.
• The chain is located in the inner mitochondrial membrane.
• It involves a series of protein complexes that pump protons (H+) across the membrane.
• The resulting electrochemical gradient is used by ATP synthase to produce ATP.

Oxidative Phosphorylation

• Oxidative phosphorylation is the process of producing ATP through the electron transport chain via electrochemical gradient.
• ATP synthase generates ATP using the energy from hydrogen proton gradient.

Total ATP production from glucose breakdown

• 30-32 ATP molecules are produced per one glucose molecule in total aerobic respiration—these numbers vary slightly depending on different cellular conditions and efficiency.

Non-ETC Oxygen-Consuming Reactions

• Processes not directly involving the electron transport chain but crucial for cellular respiration, like fermentation, which allows glycolysis to proceed in the absence of oxygen.

Metabolic Pathways of Vitamins

• Many B vitamins are important for several metabolic pathways in cells, acting as cofactors or participants in critical enzymatic reactions.

Other Relevant Metabolic Processes

• Gluconeogenesis: Producing glucose from non-carbohydrate substrates when glucose levels are low.
• Pentose Phosphate Pathway (PPP): Producing NADPH and ribose-5-phosphate for biosynthetic processes.
• Urea Cycle (Ornithine Cycle): Removing ammonia from cells, a toxic byproduct, converting it into urea for excretion.
• Amino Acid Metabolism: Breaking down and synthesizing amino acids for protein synthesis and other cellular functions.
• Cholesterol Metabolism: Synthesizing and utilizing cholesterol for various cellular processes.
• Beta-Oxidation: Breaking down fatty acids to produce acetyl-CoA in the presence of oxygen, a significant energy source.
• Fermentation: Producing ATP in the absence of oxygen.

Important Note

• The exact numbers for ATP production might vary slightly depending on the specific conditions and pathways involved in a cell.