Metabolic Pathways and Bioenergetics

Metabolic Pathways

• Metabolism is a complex network of interconnected pathways
• Metabolic pathways are interconnected for optimal energy usage and cellular function
• Pathways include biodegradation of xenobiotics, metabolism of complex carbohydrates, complex lipids, lipids, energy, carbohydrates, nucleotides, amino acids, other amino acids, cofactors, vitamins, and biosynthesis of secondary metabolites.

Bioenergetics and Metabolism

• Metabolism is a complex, interconnected process
• Metabolic pathways are involved in the storage, use, and production of energy
• All pathways are interconnected

Cellular Respiration

• Cellular respiration describes how organisms acquire and transform energy to perform biological work
• It includes different biological processes leading to ATP and equivalent nucleotide production
• Divided into catabolism (breakdown of molecules to obtain energy) and anabolism (synthesis of compounds needed by cells)

Macronutrients, Catabolism, and Anabolism

• Macromolecules include proteins, polysaccharides, lipids, and nucleic acids
• Energy-containing nutrients, like carbohydrates, fats, and proteins, are broken down in catabolism
• Catabolism releases chemical energy, which anabolism uses for synthesis

Types of Cell Respiration

• Aerobic respiration uses oxygen to produce 30 ATP per glucose molecule
• Anaerobic respiration does not use oxygen; it produces fewer ATPs and uses different oxidants

Energy Usage

• Energy is used in synthesis of macromolecules, muscle contraction, signal transmission in neurons, transport across cell membranes, and heat production.
• Fatty acid oxidation is aerobic; glucose oxidation is anaerobic
• Aerobic respiration needs mitochondria and oxygen.

Entropy and Enthalpy

• Entropy measures a system's unavailable thermal energy for useful work
• Enthalpy is a state function depending on internal energy, pressure, and volume; it simplifies energy transfer description
• At constant pressure, enthalpy changes equal energy transferred from the environment through heating or non-expansion work.
• Change in enthalpy is positive for endothermic reactions and negative for exothermic processes.

Redox Reactions

• Redox reactions involve changes in oxidation numbers due to electron gain/loss
• Coupled reactions in which one molecule gains electrons (reduction) while another loses them (oxidation)
• Oxidation is loss of electrons; reduction is gain of electrons

High Energy Phosphate

• ATP is formed by binding a phosphate molecule to ADP for energy storage
• ATP releases a phosphate ion when providing energy for cellular metabolism, regenerating ADP.
• ADP can release more phosphate ions and generate AMP or non-phosphorylated adenosine

Oxidative Phosphorylation

• Oxidative phosphorylation forms ATP through electron transfer from NADH or FADH2 to oxygen via electron carriers
• It captures energy as a proton gradient used in chemiosmosis to create ATP
• In eukaryotes, this process occurs primarily in the mitochondria

Electron Transport Chain

• Electron transport chain (ETC) transfers electrons from donors to acceptors via redox reactions
• Couples electron transfer with proton transfer across a membrane, creating an electrochemical proton gradient for ATP synthesis
• Final electron acceptor in aerobic respiration is O2; involves various peptides and enzymes

Substrate Level Phosphorylation

• Substrate-level phosphorylation directly phosphorylates ADP using energy from a coupled reaction
• Oxidative phosphorylation generates ATP from NADH and FADH2 oxidation, transferring electrons and pumping protons

Carbohydrate Metabolism

• Stage 1: Digestion and hydrolysis break down large carbohydrates into smaller molecules absorbed into bloodstream
• Stage 2: Degradation breaks down molecules into two or three-carbon compounds
• Stage 3: Oxidation of small molecules via citric acid cycle and electron transport produces ATP

Glycolysis

• Glycolysis is a metabolic pathway that converts glucose into pyruvate
• It requires no oxygen (anaerobic)
• It occurs in cytoplasm and produces energy
• A-five reactions consume energy, B-five reactions produce energy

TCA Cycle

• The TCA Cycle is an aerobic metabolic pathway in mitochondria that oxidizes acetyl-CoA, producing energy in the form of ATP.
• Oxidizes acetyl-CoA derived from carbohydrates, fats, and proteins
• Produces CO2 and other molecules for energy

Glycogenesis

• Glycogenesis stores glucose as glycogen in liver and muscles
• This occurs when glucose-6-phosphate levels are high
• Glycogen stores are not full when additional glucose is converted to fat.

Glycogenolysis

• Glycogenolysis breaks down glycogen into glucose
• This occurs when blood glucose levels are low
• Glucose-1-phosphate is formed, and further processing (conversion) yields free glucose

Gluconeogenesis

• Gluconeogenesis generates glucose from non-carbohydrate sources (i.e., not glycogen)
• This is important for the body when glycogen stores are low or it can't utilize glucose
• Non-carbohydrate sources include amino acids and lipids

Pentose Phosphate Pathway (PPP)

• PPP is a metabolic pathway parallel to glycolysis
• It generates NADPH and pentoses (5-carbon sugars) and ribose-5-phosphate for nucleotide synthesis

Lipid Metabolism

• Lipid metabolism involves fat synthesis, as well as breakdown
• Lipids are stored for energy consumption or synthesis
• End products are carbon dioxide, water, and ATP
• Complete combustion of fatty acids requires glucose or ketone production

Steps of Lipid Digestion and Absorption

• Minor digestion (TAGS → DAGs + FFA) occurs in the mouth and stomach
• Major digestion (TAG → MAG + 2FFA (PL); CE → chol. + ester (CE);PL → FA + lysoPL (PLA))—happens in the lumen of the small intestine
• Formation of mixed micelles (bile salts) occurs in the lumen of the small intestines
• Passive absorption of lipolytic products into the intestinal epithelial cell, and exported to the lymphatics

Fatty Acid Synthesis

• Fatty acids are synthesized in the cytoplasm from acetyl-CoA and NADPH produced in mitochondria through the citrate-malate-pyruvate shuttle or the pentose phosphate pathway
• The liver converts excess carbohydrates and proteins into fatty acids and triglycerides
• The liver produces large amounts of cholesterol and phospholipids

Lipogenesis

• Lipogenesis is a metabolic process in which acetyl-CoA is used to synthesize triglycerides for storage in adipose tissues
• Converted from carbohydrates

Lipolysis

• Lipolysis breaks down triglycerides in adipose tissue into fatty acids and glycerol
• Fatty acids are transported in the blood for use in beta-oxidation and ATP production
• Regulated by the nervous system and hormonal factors

Beta Oxidation of Fatty Acids

• Beta-oxidation is a metabolic pathway that breaks down fatty acids into acetyl-CoA to produce ATP
• Follows a recurring sequence of four reactions, shortening the fatty acyl chain by two carbons each cycle
• Generates FADH2, NADH, and acetyl-CoA

Ketogenesis

• Ketogenesis produces ketone bodies from fatty acids
• Crucial during periods of prolonged fasting or starvation

Protein Metabolism

• Proteins are too large to be absorbed and require hydrolysis by proteolytic enzymes
• Proteolytic enzymes are produced in the stomach, pancreas, and small intestine
• These enzymes break down proteins into amino acids, which are absorbed easily

Amino Acid Catabolism

• The first step of amino acid catabolism is removing a-amino groups to form ammonia and a-keto acids
• The second step involves conversion of a-keto acids to intermediates of energy production, like glucose, fatty acids, or ketone bodies

Overall Nitrogen Metabolism

• Nitrogen enters the body from food
• It leaves the body in the form of urea, ammonia, and other products of amino acid metabolism