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Introduction to Metabolism. Objectives. Understand the concept of metabolic pathway Identify types & characters of metabolic pathways- anabolic and catabolic Identify ATP as the energy currency of cells Understand the transport of major metabolic fuel- Glucose. Metabolism.
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Objectives • Understand the concept of metabolic pathway • Identify types & characters of metabolic pathways- anabolic and catabolic • Identify ATP as the energy currency of cells • Understand the transport of major metabolic fuel- Glucose
Metabolism • All the chemical reactions taking place inside a cell are collectively known as METABOLISM
Metabolism • Metabolic Pathways arechemicalreactionsorganized in multistepssequences where: • The product of one reaction of the pathway serves as substrate of the subsequent reaction • Most pathways can be classified as anabolic(synthetic) or catabolic (degenerative) • Integrated pathways= Metabolism
Basic functions of metabolism • To obtain energy from fuel molecules • To convert nutrients into precursors of cellular components. 3. To assemble precursors utilizing energy into cellular components.
ANABOLICCATABOLIC large complex organic molecules are constructed from small molecules Decomposition of large complex molecules into smallmolecules Biosynthetic Degradative Reductive Oxidative Energy Required Energy Liberated Diverging Converging
Catabolism Anabolism (diverging) (converging) Few Many Many Few
Anabolic Pathway • Combine small moles as a.a. to form complex as ptn • It is a divergent process w needs ATP (endergonic) & reducing power (mostly NADPH)
Macromolecules Proteins Polysaccharides Lipids Nucleic acids Nutrients Carbohydrates Fats Proteins GTP ATP NADPH Catabolism(oxidative, exergonic) Anabolism (reductive, endergonic) NADPH Chemical energy NADPH NADH ATP ATP Precursor Molecules Amino acids Sugars Fatty acids Nitrogenous bases End products H2O, CO2, NH3 Catabolism and anabolism are always related.
Amphibolic Pathway Amphi = Dual, amphibolic: dual pathway For example, Krebs cycle is mainly a catabolic cycle, but with some anabolic features, e.g., part of Krebs cycle is used for the synthesis of glucose from amino acids Therefore, Krebs cycle is amphibolic
Metabolic Map • Different pathways can intersect, forming an integrated and purposeful network of chemical reactions “The Metabolic Map”
Chemical energy • ATP - energy currency. It serves as the driving force for nearly all biochemical processes • NADH,NADPH - reducing power. NADH for oxidation and energy yielding. NADPH for biosynthetic processes
ATP is the energy currency of the cell ATP + H2O ADP +Pi • The free energy liberated in the hydrolysis of ATP is used to drive the endergonic reactions • ATP is formed from ADP and Pi when fuel molecules are oxidized • This ATP-ADP cycleis the fundamental mode of energy exchange in biological systems
Adenosine Triphosphate (ATP) Δ Gº -7.3 kcal/mol/bond
Oxidation-Reduction in Metabolism E-rich compounds e.g., E-rich reduced coenzymes Oxidation ETC
Oxidation/Reduction Oxidation: Loss of hydrogen Loss of electrons Reduction: Gain of hydrogen Gain of electrons
Intracellular Regulation • Imp. for moment-to-moment regulation of metabolism which elicit rapid responses by: • availability of substrate • product inhibition or • alteration in the levels of allosteric activators or inhibitors
Intercellular Regulation • Provides long-range integration of metabolism • Usually is slower than intracellular signals, it is done by : surface to surface • the most important is • chemical signaling by hormones or neurotransmitters • This results in the production of second messengers
Metabolic Fuel Carbohydrates & lipids (mainly) and proteins (little extent) are used for energy production These are- glucose, fatty acids and amino acids Glucose is the major metabolic fuel of most tissues
Glucose Transport Na+-Monosaccharide Cotransporter: Against concentration gradient Energy dependent Carrier-mediated Coupled to Na+ transport Small intestine, renal tubules & choroid plexus Na+-Independent Facilitated Diffusion: With concentration gradient Energy Independent Glucose Transporters (GLUT 1-14)
Glucose Transporters • Tissue-specific expression pattern • GLUT-1 RBCs and brain • GLUT-2 Liver, kidney & pancreas • GLUT-3 Neurons • GLUT-4 Adipose tissue & skeletal muscle • GLUT-5 Small intestine & testes • GLUT-7 Liver (ER-membrane) • Functions: • GLUT-1, 3 & 4 Glucose uptake from blood • GLUT-2 Blood & cells (either direction) • GLUT-5 Fructose transport
Take Home Message • Metabolism is the sum of all biochemical pathways that occur inside the cells. • A metabolic pathway is a multistep sequences of enzyme-catalyzed reactions.
Catabolism is a convergent process that provides energy to cells in the form of ATP. Anabolism is a divergent process that consumes energy for the synthesis of complex molecules. Metabolic pathways are tightly regulated and highly integrated.
ATP is the energy currency of the cells Glucose is transported in/out of the cells by: Energy-dependent active transport Energy-independent facilitated transport