Carbohydrates 2 VP 2024 PDF

METABOLISM C A R B O HY DR A T E S Cellular reactions rarely occur in isolation, but as part of PATHWAYS that are MULTI-STEP sequences.  One product serves as the substrate of the next reaction Catabolic (degradative)- break down Anabolic (synthetic)- build up  Cycles: pathways that end up with th...

METABOLISM C A R B O HY DR A T E S Cellular reactions rarely occur in isolation, but as part of PATHWAYS that are MULTI-STEP sequences.  One product serves as the substrate of the next reaction Catabolic (degradative)- break down Anabolic (synthetic)- build up  Cycles: pathways that end up with the regeneration of a component The sum of all chemical reactions occurring in a cell, a tissue, a body is called: METABOLISM METABOLISM C A R B O HY DR A T E S Catabolic pathways: degradation of molecules into smaller units which can be oxidized to release energy or used in other anabolic reactions. Anabolic pathways: combine small molecules (e.g. amino acids) to form more complex molecules (e.g. proteins) → Require energy: usually in the form of ATP Stages of catabolism for ATP production From: Harvey & Ferrier. Biochemistry C A R B O HY DR AT E S LET’S TALK ENERGY Most all basic products of digestion are processed by their respective cellular metabolic pathways to a common product: ACETYL-COA ACETYL-COA can then be coupled with OXALOACETATE and oxidized in the mitochondria to:  CO2  H2O  ATP REGULATION OF METABOLISM C A R B O HYDR A T E S Available nutrients, hormones and neurotransmitters provide regulatory signals to coordinate metabolic functions, and influence signals from within cells Intracellular communication o Substrates availability, product inhibition, activators/inhibitors Intercellular communication o Direct cell surface contact, gap junctions, chemical signaling (hormones, neurotransmitters) Second messenger system o Signal transduction and cellular response o GPCR (G-protein coupled receptors) GLUCOSE TRANSPORT C A R B O HY DR A T E S Glucose transport into cells:  Glucose cannot diffuse into cells (it’s hydrophilic), it must be transported by transporters: 1. GLUT transporters o Passive system (do not require ATP)➔ it goes along the concentration gradient o GLUT-1 to GLUT-14 o Highly tissue specific o Some are insulin responsive (GLUT 4) 2. SGLT-1 transporter o Na⁺- dependent cotransporter o Can transport glucose against its concentration gradient  ATP- dependent antiport system Na+/K+- ATPase (pump) Energy-requiring process Will maintain the Na⁺ gradient (intra and extracellular) to facilitate SGLT cotransport GLUT = glucose transporter, SGLT-1 = (Na+)-dependent glucose cotransporter Na+K+ ATPase GLYCOLYSIS  Glycolysis is a central ATP- producing pathway In most organisms, glycolysis takes place in the cell cytosol in all tissues Highly regulated process (just enough glucose being metabolized at any one time to meet the cell’s need for ATP) Do not depend on oxygen!  Net gain: 2 pyruvate + 2 NADH + 2 ATP  Can be aerobic or anaerobic Red blood cells (erythrocytes) and muscle take advantage of anaerobic glycolysis C A R B O HY DR A T E S GLYCOLYSIS – Anaerobic (Absence of O2) C A R B O HY DR A T E S  NADH unload the H⁺ on pyruvate, reducing it to lactate (in eukaryotic cells) Pyruvate reduced to lactate → Fermentation!  Fermentation: extraction of energy in absence of oxygen Quick energy requirements (“flight” response) Tissue with low mitochondria density and poorly vascularized (cornea, lens) Skeletal muscle (white fibers) Cells lacking mitochondria (erythrocytes) LDH= lactate dehydrogenase GLYCOLYSIS – Anaerobic (Absence of O2) C A R B O HY DR A T E S Net gain of anaerobic glycolysis  2 ATPs for each molecule of glucose  2 molecules of lactate (animals) or ethanol (yeast)  NAD+ What happens to LACTATE? → Liver and heart can use lactate as source of energy In the liver, lactate can be converted to glucose via Cori cycle and gluconeogenesis, or lactate will follow reverse reaction to pyruvate and enter the TCA cycle as Acetyl-CoA. Heart only oxidizes lactate to pyruvate and acetyl-CoA to enter the TCA cycle. GLYCOLYSIS - Aerobic C A R B O HY DR A T E S (O2 is available)  Pyruvate will enter the mitochondria converted into acetyl-CoA (link reaction)  NADH will unload H⁺ ➔ ETC ➔ regenerate NAD+ C A R B O HY DR A T E S GLYCOLYSIS - Aerobic (O2 is available) In aerobic conditions, approximately 42% of the energy of glucose is captured in the form of ATP The remaining energy in glucose generates heat, which aids in the regulation of body temperature Eventually, all energy derived from glucose oxidation is released as heat after ATP is used up while serving its numerous purposes FATES OF PYRUVATE 1. Pyruvate reduction to lactate (fermentation) Production of ATP in absence of oxygen (i.e., RBC, poorly vascularized tissues, intensely exercising muscle tissues) 2. Pyruvate reduction to ethanol (fermentation) microorganisms (yeasts), NOT mammals 3. Oxidative decarboxylation to acetyl-CoA By PDHC-enzyme complex (pyruvate dehydrogenase complex) In tissues with high oxidative capacity Acetyl-CoA: substrate for TCA cycle and carbon source for fatty acid synthesis 4. Pyruvate carboxylation to oxaloacetate (OAA) Replenishes this important TCA cycle intermediate Provides substrate for gluconeogenesis MITOCHONDRIA C A R B O HY DR A T E S “Biochemical energy reactors of the cell" Most of the ATP is produced in the mitochondria Important Biochemical Events: o Conversion of pyruvate into Acetyl-CoA (link reaction - oxidative decarboxylation) o TCA (Krebs) cycle o Electron transport chain (ETC) o Oxidative phosphorylation o ß-oxidation (lipid metabolism) Cellular Respiration Diagram. Credit: Thoughtco.com C A R B O HY DR A T E S TCA CYCLE Tri Carboxylic Acid - cycle (Krebs cycle, Citric Acid Cycle CAC)  Final pathway where carbohydrates, amino acids, and fatty acids converge  Energy provided by the TCA cycle is essential for most animals including humans  TCA cycle location: mitochondria matrix Glycolysis TCA CYCLE C A R B O HY DR A T E S Tri Carboxylic Acid - cycle (Krebs cycle, Citric Acid Cycle CAC) TCA is An open traffic circle (like a SKN round-a-bout!!) Occurs close to the Electron Transport Chain (ETC)  where coenzymes NADH and FADH2 will be oxidized Aerobic because oxygen is the final electron acceptor (in ETC) 2 carbons enter as acetyl-CoA (ACoA), 2 leave as CO2 OXIDATIVE PHOSPHYORYLATION - (OXPHOS) Energy-rich molecules (such as glucose and fatty acids) are metabolized by a series of oxidation reactions into ATP, CO2 and H2O  Glucose → Aerobic glycolysis  Fatty acids → Beta-oxidation  Reaction metabolic intermediates donate electrons to specific coenzymes: NAD+ & FAD ➔ forms energy-rich reduced forms NADH & FADH2 NADH and FADH₂ donate a pair of electrons to the Electron Transport Chain (ETC) → located on the mitochondria INNER MEMBRANE C A R B O HY DR AT E S OXIDATIVE PHOSPHYORYLATION As electrons are passed down the ETC, they create a H+ gradient that drives ATP synthase to produce ATP (from ADP and inorganic phosphate) Oxidative Phosphorylation = Electron Transport Chain (ETC) + ATP synthesis This happens continuously in all tissues that have MITOCHONDRIA