Energy Metabolism Pathways

Major Energy Metabolism Pathways Review

• Glycolysis converts glucose to pyruvate, yielding 2 ATP and 2 NADH, and occurs in the cytoplasm under anaerobic conditions in skeletal muscle and brain cells
• The TCA Cycle oxidizes acetyl-CoA to CO2, producing 2 GTP, 6 NADH, and 2 FADH2 per glucose in the mitochondrial matrix during aerobic metabolism; pyruvate dehydrogenase complex converts pyruvate to acetyl-CoA
• Electron Transport & Oxidative Phosphorylation uses NADH and FADH2 to generate a proton gradient, driving ATP synthesis in the mitochondrial matrix, generating 32 ATP from one glucose molecule
• Photosynthesis converts 6 CO2 and 6 H2O into glucose and O2, requiring 18 ATP and 12 NADPH through light and dark reactions in the chloroplast-thylakoid membrane; 8 quanta yields 1 O2 which can produce 2.57 ATP
• Gluconeogenesis converts 2 pyruvate (from lactate or glycerol) into glucose, and requires 6 ATP. It happens in the cytoplasm, with pyruvate carboxylase in the mitochondria, bypassing three irreversible glycolytic enzymes in the liver

Glycogen, Pentose Phosphate, Fatty Acids, Amino Acids & Nucleotides

• Glycogen degradation breaks down glycogen using glycogen phosphorylase to form Glycogen-1-P, influenced by insulin
• Glycogen biosynthesis synthesizes glycogen from UDP-Glucose using glycogen synthase, influenced by glucagon/epinephrine
• The pentose phosphate pathway converts glucose-6-P to Ribose-5-P and NADPH in the cytoplasm of the liver and adipose tissue
• Fatty acid degradation (β-oxidation) breaks down fatty acids into acetyl-CoA in the mitochondrial matrix through oxidation, hydration, and cleavage
• Synthesizing fatty acids from acetyl-CoA in the cytoplasm of liver and adipose tissue requires ACP, NADPH, and Malonyl-CoA through C-C bond formation, reduction, dehydration, and reduction
• Amino acids undergo nitrate assimilation (NO3- → NH4+) and nitrogen fixation (N2 → NH4+) with NH4+ converted to organic N (CPS-I, GDH, GS) using pyruvate, OAA, 3PG, and αKG
• Nucleotides synthesis starts with adding atoms to R5P for purines or forming the pyrimidine ring first, with purines ultimately forming uric acid and pyrimidine degrading into NH4+ + CO2 + alanine

Metabolic Pathway Intermediates

• Few metabolites act as branch points linking pathways
• Glucose-6-Phosphate links glycolysis, glycogen metabolism, and the pentose phosphate pathway
• Pyruvate, oxaloacetate, and α-ketoglutarate link amino acid metabolism, glucose metabolism, and pyruvate metabolism
• Phosphoenolpyruvate links glycolysis and gluconeogenesis as a high-energy phosphate compound
• Acetyl-CoA and succinyl-CoA connect amino acid metabolism and serve as degradation products in catabolism, are an offshoot of fatty acid beta-oxidation
• NADH and FADH2 act as electron acceptors in glycolysis, PDC, TCA cycle, beta-oxidation and electron donors in oxidative phosphorylation reactions
• ATP and NADPH are the only two compounds that directly link catabolism with anabolism

ATP Coupling and Thermodynamics

• Thermodynamically unfavorable reactions of anabolism are driven by energy released upon ATP hydrolysis
• During respiration, C6H12O6 + 6 O2 are converted to 6 CO2 + 6 H2O, maintaining the same number of atoms before and after the reaction
• Obligate Coupling Stoichiometry involves coupling biological electron donors and acceptors, leading to 6 O2 reduction to 12 H2O
• Stoichiometry of ATP in metabolism results from biological adaptation & evolution
• Chemiosmotic coupling hypothesis: A proton gradient drives ATP synthesis and consensus P/O ratio
• Two main roles of ATP: energy coupling reactions and allosteric regulation

Energy Balance Regulation

• AMP-activated protein kinase (AMPK) acts as the cellular energy sensor, regulating cellular energy homeostasis
• AMPK is inactive when ATP levels are high, and allosterically activated when ATP levels are low
• Allosterically activated AMPK phosphorylates targets, controlling cellular energy production and consumption when ATP is low
• AMPK is an αβγ heterotrimer, where the α-subunit is the catalytic subunit and the γ-subunit is regulatory; the β-subunit includes an αγ-binding domain
• Eating behavior, hormones, and exercise affect AMPK activation
• Leptin and adiponectin activate AMPK
• Insulin secretion, fatty acid synthesis, cholesterol synthesis, and gluconeogenesis all suppress AMPK
• Fatty acid uptake and oxidation, glucose uptake, and mitochondrial biogenesis activate AMPK

Metabolic Integration in Multicellular Organisms

• Organ systems in complex multicellular organisms arose to fulfill specific functions
• Specialization relies on coordinated metabolic responsibilities among organs for organismal thriving
• Organs vary in the fuels preferred as substrates for energy production
• In animals, key fuel depots include glycogen in liver and muscle tissue, triacylglycerols in adipose tissue, and protein primarily in skeletal muscle
• Preference for energy is glycogen>triacylglycerol>protein
• Brain: Glucose (ketone bodies during starvation), None
• Skeletal muscle (resting): Fatty acids, None
• Skeletal muscle (strenuous exercise): Glucose from glycogen, Lactate
• Heart muscle: Fatty acids, None
• Adipose tissue: Fatty acids, glycerol
• Liver: Amino acids, glucose, fatty acids, Fatty acids, glucose, ketone bodies

Phosphocreatine & Glucose-6-Phosphate

• Phosphocreatine buffers ATP levels via ATP Recycling
• Phosphocreatine + ADP creatine + ATP, providing energy to muscles
• Supports instantaneous needs for short-duration, high-intensity activities like weightlifting
• Glucose-6-phosphate provides a source for prolonged ATP generation
• Fate of G6P includes blood glucose, glycogen, acetyl-CoA for energy, acetyl-CoA for FA & cholesterol synthesis, and pentose phosphate pathway to make NADPH & ribose-5-phosphate

Creatine Supplements

• The creatine pool in a 70-kg human is about 120 grams
• About 95% of creatine stores are in skeletal and smooth muscles, with 70% as phosphocreatine
• Supplementing with 20 to 30 grams of creatine daily for 4-21 days can increase muscle creatine by up to 50%
• Supplementation can improve performance in high-intensity, short-duration events, but not endurance events
• The FDA advises consulting a physician before creatine supplements

Metabolic Profiles of Six Tissue Types

• Brain: Uses 20% of the total energy demands of the whole body, prefers glucose from a bloodstream, uses no fuel reserves or glycogen, fats or protein, uses ketone bodies synthesized from the liver, which uses fatty acid beta-oxidation
• Heart Muscle: Maintains continuous activity, uses fats(preferred), as well as glucose from limited stores of glycogen, pyruvate, and lactate keto bodies can be used, and needs aerobic metabolism
• Adipose Tissue: Long-therm energy storage, uses 15kgs of fats sustainable for 3 months, esterifies glycerol with fatty acids if glucose is available, and uses brown fat to uncouple the electron transport change to produce heat instead of ATP
• Liver: The central hub for the metabolism in the body uses glycogen and amino acids for the body's nutrients and levels
• Kidney: Filters product urea, maintains the blood, generates 50% glucose

Metabolic Responses to Stressful Conditions

• Humans and animals respond quickly to stresses that can unbalance metabolism
• Right after a meal, blood glucose and insulin secretions increase while fatty acid synthesis and glucose abundance stored in glycogen is used and maintained
• A few hours after a meal, the body uses glycogen in the liver while glucose synthesis in the liver is transported to the brain
• Starvation/Fasting utilizes glycogen, triaclyglycerols, and protein reserves
• Fat degradation creates ketone bodies in the liver to help replenish the brains glucose needs
• Ketosis can lead to acidosis which leads to coma and death
• The body is forced to use biochemical adjustments in moderation while Dieting (a.k.a the Atkins Diet)
• Side effects of the Atkins Diet is dehydration, an electrolyte imbalance, bad breath, osteoporosis, and depression
• Diabetes (Type I and II) means that the body is losing its main source
• Exercise: Sprinting uses Anaerobic metabolism to increase the amount of II muscle fiber, while Endurance can increase the amount of I muscle fibers

Biochemical Factors in Obesity

• Obesity is 20% over an ideal standard weight, causing diabetes, heart disease, high blood pressure, stroke and cancers
• Factors regulated by the neuroendocrine system controlled hormones include Ghrelin, Leptin and GLP-1
• Ghrelin signals hunger by increasing appetite
• Leptin decreases appetite in order to regulate energy, by stimulating hormone secretions
• GLP-1 aids in the absorption of fat cells and in the liver