A&P Metabolism 1 - Cellular Respiration and Glycolysis

• Metabolism encompasses all chemical reactions in the body.
• Metabolism is the sum of cellular catabolism and anabolism.
• ATP, generated through metabolism, links anabolic and catabolic reactions.

Catabolism

• Catabolism breaks down complex molecules into simpler ones.
• Catabolic reactions are exergonic, releasing energy stored in the molecules.

Anabolism

• Anabolism combines simple molecules into complex ones.
• Anabolic reactions are endergonic, requiring energy.

Aerobic Metabolism (Cellular Respiration)

• Requires oxygen and occurs in the mitochondria.
• Captures 40% of energy released as ATP, with the remaining 60% escaping as heat.

ATP (Adenosine Triphosphate)

• ATP is the "energy currency" of the body.
• Energy is stored in the bonds between phosphate groups.
• ATP is created in exergonic reactions, e.g., glycolysis, and used in endergonic reactions, e.g., glycogenesis.
• Requires energy to reattach P back on.

Nutrient Pool

• The nutrient pool comprises available organic substrates for catabolism and anabolism.
• Anabolism in cells is required for replacing membranes, organelles, enzymes, and structural proteins.
• Catabolism in cells is required for converting substrates into a 2-carbon molecule that mitochondria use to produce ATP.

Nutrient Utilization

• Nutrients come from the diet and from reserves.
• Reserves are mobilized when absorption across the digestive tract is insufficient to maintain normal nutrient levels.
• The liver breaks down triglycerides and glycogen, releasing fatty acids and glucose.
• Adipocytes break down triglycerides, releasing fatty acids.
• Skeletal muscle cells break down contractile proteins, releasing amino acids.

Nutrient Reserves

• Reserves are stocked when absorption by the digestive tract is greater than immediate nutrient needs.
• Liver cells store triglycerides and glycogen.
• Adipocytes convert excess fatty acids to triglycerides.
• Skeletal muscles build glycogen reserves and use amino acids to increase the number of myofibrils

Aerobic vs. Anaerobic

• Aerobic: "with oxygen"; Anaerobic: "without oxygen."
• Aerobic exercise involves continuous activities that increase heart rate, uses oxygen to produce energy, and releases more energy but more slowly.
• Anaerobic exercise involves short, intense activities, uses energy stored in muscles, and releases less energy but more quickly.
• Aerobic examples: walking, running, jogging, swimming.
• Anaerobic examples: sprinting, interval training, weight lifting.

Glucose as Primary Resource

• Nervous tissue requires a continuous supply of glucose.
• During starvation, other tissues can shift to fatty acids, amino acids, or ketones to conserve glucose for nervous tissue.

Oxidation and Reduction (REDOX)

• Oxidation is the removal of electrons from a molecule (typically involves loss of hydrogen atoms).
• Reduction is the addition of electrons to a molecule.
• Oxidation and reduction reactions are always paired.
• Two common coenzymes used in redox reactions are NAD (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide).
• NAD+ is reduced to NADH + H+; FAD is reduced to FADH2

ATP Generation Mechanisms

• Substrate-level phosphorylation: Transferring a high-energy phosphate group from an intermediate directly to ADP.
• Occurs in glycolysis, citric acid cycle, and phosphocreatine.
• Oxidative phosphorylation: Removing electrons and passing them through an electron transport chain to oxygen.

Carbohydrate Metabolism

• Glucose is the breakdown product of carbohydrates absorbed in the small intestine.
• Glucose is the preferred energy source because it:
• Is a small, soluble molecule easily distributed throughout body fluids.
• Can provide ATP anaerobically through glycolysis.
• Can be stored as glycogen.
• Can be easily mobilized via glycogenolysis.
• GluT transporters bring glucose into the cell via facilitated diffusion (Insulin increases GluT expression in the plasma membrane.)
• Glucose is trapped in cells after being phosphorylated

Glucose Fate

• ATP production (immediate energy need)
• Glycogen synthesis (storage)
• Amino acid synthesis (protein formation)
• Triglyceride synthesis (fat storage when other stores are full)

Glucose Utilization Steps

• Glycolysis (anaerobic)
• Formation of Acetyl Coenzyme A (aerobic)
• Citric Acid Cycle Reactions/Krebs Cycle (substrate-level phosphorylation)
• Electron Transport Chain Reactions (aerobic/oxidative phosphorylation)

Glycolysis

• Glycolysis splits 6-carbon glucose into two 3-carbon molecules of pyruvic acid and occurs in the cytosol.
• Glycolysis involves 10 reactions, consumes 2 ATP, but generates 4, resulting in a NET GAIN of 2 ATP
• Starting product: one glucose, end product: two pyruvate molecules.
• Byproducts: 2 NADH, 2 ATP.
• Location: cytosol.

Rate-Limiting Enzyme

• Phosphofructokinase (slowest, irreversible step in the pathway)
• Glycolysis is anaerobic

Pyruvate Fate

• Depends on oxygen availability
• If oxygen is scarce (anaerobic): pyruvate is reduced to lactic acid
• If oxygen is plentiful (aerobic): pyruvate is converted to acetyl coenzyme A and it enters the Citric Acid Cycle

Pyruvate with Scarcity of Oxygen

• 2 pyruvic acid + 2 NADH + 2H+ -> 2 lactic acid + 2 NAD+
• NAD+ must be regenerated to allow glycolysis to continue

Cori Cycle

• Lactate is released to the blood stream which is taken up by the liver (hepatocytes) which turns it back into glucose.
• Glucose requires 6x ATP

Acetyl Coenzyme A Formation

• This process is the second step in cellular respiration.
• If O2 is present this reaction occurs
• One pyruvic acid molecule is converted to a 2-carbon acetyl group.
• One molecule of CO2 is removed as waste.
• Pyruvic acid enters the mitochondria first and then is converted to acetyl coenzyme A. Each pyruvic acid also loses 2 hydrogen atoms (NAD+ reduced to NADH/H+)
• CO2 released is breathed out
• For 1 glucose molecule: Starting Product = 2 pyruvate
• End Product = 2 acetyl Coenzyme A Byproducts = 2 CO2, 2 NADH
• Location: mitochondrial matrix
• The oxidizing enzyme used, is Pyruvate Dehydrogenase which reduces NAD to NADH.

Citric Acid Cycle (CAC) (Krebs Cycle/Tricarboxylic Acid Cycle)

• This is the second step of cellular respiration (aerobic).
• CAC occurs in the matrix of mitochondria.
• Series of REDOX reactions transfer energy to coenzymes.
• The reduced coenzymes NADH and FADH2 are the most important outcome.
• For every one acetyl CoA that enters the CAC, 3NADH + 3H+ + 1 FADH2 + 1 ATP is produced.
• Acetyl CoA enters the cycle for it to happen.

Starting Molecule

• Starts with Oxaloacetic acid (then acetyl CoA).
• Byproducts are 2CO2, 3 NADH, 1 FADH2, and 1 ATP.
• With each glucose molecule entering the process the number of by products double.
• Only FADH2 is seen in the cycle - it is a REDOX reaction.

Electron Transport Chain

• A series of electron carriers called cytochromes are in the inner mitochondrial membrane
• Receives electrons from NADH and FADH2
• Oxygen is the final electron acceptor and more than 90% of ATP used in the body is produced
• Each electron carrier is reduced or oxidized as electrons pass along the chain
• Energy released as electrons are passed from one carrier to another pumps H+ ions into the intermembrane space, creating an electrochemical gradient
• Final electron acceptor is O2 which along with H+ creates H2O

Oxidative Phosphorylation

• Oxidative phosphorylation generates a proton motive force, an electrochemical gradient of H+ ions. H+ ions diffuse through ATP synthase enzyme to generate ATP.
• If no O2 then this entire process STOPS

Net ATP Yield

• Each NADH yields 2.5 ATP
• Each FADH2 yields 1.5 ATP
• Total: 10 NADH x 2.5 ATP/NADH = 25 ATP, 2 FADH2 x 1.5 ATP/FADH2 = 3 ATP, and 4 ATP
• = 32 ATP per glucose molecule

Key Questions and Answers

• How does glucose enter the cell? Glut transporters through facilitated diffusion
• What is the starting molecule in glycolysis? One molecule of glucose
• What is the end product of glycolysis? Two molecules of pyruvic acid
• What is the net gain of ATP? 2 ATP (produces 4 but uses 2)
• What happens to pyruvic acid in an anaerobic environment? Reduced to form lactic acid which diffuses into the blood
• What happens to pyruvic acid in an aerobic state? Converted to acetyl CoA to enter CAC
• Where is acetyl CoA formed? In the mitochondrial matrix
• What is the overall purpose of CAC? Reduced coenzymes that carry potential energy (NADH and FADH2)
• What happens to the CO2 produced in the CAC? Diffuses out of mitochondria, out of plasma membrane, into the blood where it is transported to the lungs to be exhaled
• In the ETC, how many ATP will a molecule of NADH produce? 2.5
• In the ETC how many ATPs will a molecule of FADH2 produce? 1.5
• Where is the ETC located? Inner mitochondrial membrane
• What is the pumping of H+ into the space between the membrane creating? Concentration and electrical gradient

Overview

• Glycolysis: 2 NADH, 2 ATP
• Formation of Acetyl CoA: 2 NADH
• Citric Acid Cycle: NADH 6, FADH2 2, ATP 2

Explore the citric acid cycle's role, NADH production, and impacts of pyruvate conversion. Understand glycolysis, net energy production, and enzyme inhibition. Discover pyruvate's fate and substrate-level phosphorylation.