Biochemistry: Glycolysis and Energy Production

Biochemistry of Cell - Week 9 Lectures

• Carbohydrates are the primary energy source in the diet.
• Complex carbohydrates (disaccharides and polysaccharides) are broken down by enzymes and stomach acid into monosaccharides, primarily glucose.
• Glucose is stored in the liver and muscles as glycogen until needed.
• Monosaccharides can be used to build new oligo- and polysaccharides or for energy production through glycolysis.
• Glycolysis is a metabolic pathway that converts glucose into pyruvate.

Glycolysis

• Glycolysis occurs in the cytosol of cells.
• It is primarily an anaerobic process, meaning it does not require oxygen.
• The pathway is a stepwise degradation of glucose.
• Glucose, a six-carbon molecule, is converted to two three-carbon molecules of pyruvate.
• Glycolysis involves 10 enzyme-catalyzed steps and is also known as the Embden-Meyerhof pathway.
• Glycolysis is the first metabolic pathway to be elucidated in detail, mostly by German scientists during the first half of the 20th century.

Major Pathways of Carbohydrate Metabolism

• Various pathways interrelate in carbohydrate metabolism, including glycogenesis (glycogen synthesis), glycogenolysis (glycogen breakdown), the pentose phosphate pathway, gluconeogenesis (glucose synthesis), and the citric acid cycle.
• These pathways determine how glucose is broken down, stored, and used for energy production as well as other metabolic functions.

Introduction to Glycolysis

• Glycolysis occurs in the cytoplasm of cells.
• It involves the conversion of glucose into pyruvate.
• The process is anaerobic, no oxygen is needed.
• The first step is the phosphorylation of glucose to form glucose-6-phosphate.
• This process starts by the conversion of glucose to fructose 1, 6-bisphosphate which subsequently yields 2 molecules of triose phosphate, one molecule of glyceraldehyde-3-phosphate, and one molecule of dihydroxyacetone phosphate.
• Subsequent reactions convert these to pyruvate.

Possible fates of pyruvate in glycolysis

• Under aerobic conditions, pyruvate is converted to acetyl-CoA.
• Pyruvate is oxidized by loss of carboxyl group as CO2, remaining two-carbon unit becomes the acetyl group of acetyl CoA.
• This occurs via the pyruvate dehydrogenase (PDH), which is a multi-enzyme complex in the mitochondria.
• Under anaerobic conditions, pyruvate undergoes either lactic acid fermentation or alcoholic fermentation.

The Citric Acid Cycle (CAC)

• The CAC plays a central role in both catabolism (breakdown) and anabolism (building up) of macromolecules.
• The cycle is also known as the Krebs cycle or the tricarboxylic acid cycle.
• Some of the compounds in the cycle are organic acids with 3 carboxyl groups.
• The CAC is a crucial pathway for energy production from carbohydrates, fats, and proteins.

Stages of CAC

• Stage 1: Amino acids, fatty acids, and glucose can yield acetyl-CoA. Acetyl-CoA is oxidized to CO2 and H2O.
• Stage 2: Acetyl-CoA enters the CAC.
• Stage 3: High-energy electrons and protons from NAD+ and FAD are transferred to form NADH + H+ and FADH2. Electrons enter the electron transport chain.

Oxidative Phosphorylation

• Oxidative phosphorylation is a process where energy from the electron transport chain is used to phosphorylate ADP to ATP.
• Oxidative phosphorylation is tightly linked to the oxidation of NADH and FADH2 in the presence of oxygen.
• Reduced coenzymes (NADH and FADH2) are oxidized, releasing the electrons and protons.
• These electrons are transferred through a series of electron carriers, which pumps protons (H+) from the matrix to the intermembrane space in the mitochondria, creating a proton gradient
• This proton gradient drives ATP synthesis through a protein called ATP synthase. The energy released during electron transport is used to generate a proton gradient across the inner membrane, driving ATP synthesis.

The Electron Transport Chain (ETC)

• ETC is a series of electron carriers located in the inner mitochondrial membrane.
• It involves the transfer of electrons from NADH and FADH2 to oxygen, yielding ATP.
• It consists of four enzyme complexes, each containing various prosthetic groups.

Mitochondrial Function

• Mitochondria have specific compartments where different metabolic processes occur.
• Their various complexes and enzymes are related, and localized to different membranes, and spaces.