Tema 11 B (2).pdf

METABOLISMO DE GLÚCIDOS: PARTE 2 M 1  THREE POSSIBLE CATABOLIC FATES OF THE PYRUVATE FORMED IN GLYCOLYSIS Anaerobic Aerobi...

METABOLISMO DE GLÚCIDOS: PARTE 2 M 1  THREE POSSIBLE CATABOLIC FATES OF THE PYRUVATE FORMED IN GLYCOLYSIS Anaerobic Aerobic M 2  2- ANAEROBIC GLYCOLYSIS: FERMENTATION Generation of energy (ATP) without consuming oxygen or NAD+ Reduction of pyruvate to another product Regenerates NAD+ for further glycolysis under anaerobic conditions The process is used in the production of food from beer to yogurt to soy sauce Anaerobic M 3  2.a - LACTIC ACID FERMENTATION M 4  2.a - LACTIC ACID FERMENTATION M 5  2.a - LACTIC ACID FERMENTATION M 6  ANIMALS UNDERGO LACTIC ACID FERMENTATION Reversible (isoenzymes) During strenuous exercise, lactate builds up in the muscle ✓ Generally, less than 1 minute The acidification of muscle prevents its continuous strenuous work The lactate can be transported to the liver and converted to glucose there Requires a recovery time ✓ High amount of oxygen consumption to fuel gluconeogenesis ✓ Restores muscle glycogen stores M 7  THE CORI CYCLE: METABOLIC COOPERATION BETWEEN SKELETAL MUSCLE AND THE LIVER Extremely active muscles use glycogen as energy source, generating lactate via glycolysis. During recovery, some of this lactate is transported to the liver and converted to glucose via gluconeogenesis. This glucose is released to the blood and returned to the muscles to replenish their glycogen stores. The overall pathway (glucose → lactate → glucose) constitutes the Cori cycle. M 8  2.b- ETHANOL FERMENTATION YEAST UNDERGO ETHANOL FERMENTATION La sexta reacción de la glucólisis M 9  2.b- ETHANOL FERMENTATION YEAST UNDERGO ETHANOL FERMENTATION Two-step reduction of pyruvate to ethanol, irreversible Humans do not have pyruvate decarboxylase We do express alcohol dehydrogenase for ethanol metabolism CO2 produced in the first step is responsible for: ✓ carbonation in beer ✓ dough rising when baking bread Both steps require cofactors ✓ Pyruvate decarboxylase: Mg++ and thiamine pyrophosphate (TPP) M ✓ Alcohol dehydrogenase: Zn++ and NAD+ 10  TPP IS A COMMON ACETALDEHYDE CARRIER M 11  FEEDER PATHWAYS FOR GLYCOLYSIS Glucose molecules are cleaved from glycogen and starch by glycogen phosphorylase ✓ Yielding glucose-1-phosphate Disaccharides are hydrolyzed ✓ Lactose: glucose and galactose ✓ Sucrose: glucose and fructose ✓ Fructose, galactose, and mannose enter glycolysis at different points M 12  3- GLUCONEOGENESIS: CARBOHYDRATE SYNTHESIS FROM SIMPLE PRECURSORS Animals can produce glucose from sugars or proteins ✓ Sugars: pyruvate, lactate, or oxaloacetate ✓ Protein: from amino acids that can be converted to citric acid cycle intermediates (or glucogenic amino acids) Animals cannot produce glucose from fatty acids ✓ Product of fatty acid degradation is acetyl-CoA Plants, yeast, and many bacteria can do this, thus producing glucose from fatty acids M 13  Glycolysis versus Gluconeogenesis Glycolysis and Gluconeogenesis are opposing pathways that are both thermodynamically favorable ✓ Operate in opposite direction ▪ End product of one is the starting compound of the other Reversible reactions are used by both pathways Irreversible reaction of glycolysis must be bypassed in gluconeogenesis ✓ Highly thermodynamically favorable, and regulated ✓ Different enzymes in the different pathways ✓ Differentially regulated to prevent a futile cycle Glycolysis occurs mainly in the muscle and brain. Gluconeogenesis occurs mainly in the liver. M 14  PYRUVATE TO PHOSPHOENOLPYRUVATE Requires two energy-consuming steps M 15  PYRUVATE TO PHOSPHOENOLPYRUVATE First step: Pyruvate carboxylase converts pyruvate to oxaloacetate – Carboxylation using a biotin cofactor – Requires transport into the mitochondria, via malate BIOTIN IS A CO2 CARRIER Second step: Phosphoenolpyruvate carboxykinase converts oxaloacetate to PEP – Phosphorylation from GTP and decarboxylation – Occurs in mitochondria or cytosol depending on the organism M 16 M 17 M 18  FROM PYRUVATE TO PHOSPHOENOLPYRUVATE Alternative paths from pyruvate to PEP. There is no transporter for oxaloacetate in the inner mitocondrial membrane The relative importance depends on the availability of lactate or pyruvate and the cytosolic requirements for NADH for gluconeogenesis. The path on the right predominates when lactate is the precursor, because cytosolic NADH is generated in M the lactate dehydrogenase reaction and does not have to be shuttled out of the mitochondrion 19  ADDITIONAL BYPASSES Catalyze reverse reaction of opposing step in glycolysis Are irreversible themselves Glucose 6-phosphate → Glucose ✓ By glucose 6-phosphatase Fructose 1,6-bisphosphate → Fructose 6-Phosphate ✓ By fructose bisphosphatase-1 ✓ Coordinately/oppositely regulated with PFK1 M 20 M 21  GLUCONEOGENESIS IS EXPENSIVE 2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 4 H2O → Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ Costs 4 ATP, 2 GTP, and 2 NADH physiologically necessary Brain, nervous system, and red blood cells generate ATP ONLY from glucose When glycogen stores are depleted, we need to get glucose from somewhere During starvation or vigorous exercise M 22  4- PENTOSE PHOSPHATE PATHWAY ❖ The main products are NADPH and ribose 5-phosphate NADPH is an electron donor ✓ Reductive biosynthesis of fatty acids and steroids NADPH is an electron donor ✓ Repair of oxidative damage Ribose-5-phosphate is a biosynthetic precursor of nucleotides ✓ Used in DNA and RNA synthesis ✓ Or synthesis of some coenzymes Enzymes specific for NAD+ or NADP+ NAD+ and NADP+ Cannot exchange by metabolism M 23  4- PENTOSE PHOSPHATE PATHWAY 1-OXIDATIVE PHASE GENERATES NADPH AND R-5-P [NADPH] inhibits the first enzyme in the pentose phosphate pathway. NADPH REGULATES PARTITIONING INTO GLYCOLYSIS VS. PENTOSE PHOSPHATE PATHWAY When NADPH is forming faster than it is being used for biosynthesis and glutathione reduction, [NADPH] rises and inhibits the first enzyme in the pentose phosphate pathway. As a result, more glucose 6- phosphate is available for glycolysis. M 24  2- NON-OXIDATIVE PHASE REGENERATES G-6-P FROM R-5-P Used in tissues requiring more NADPH than R-5-P ✓ Such as the liver and adipose tissue M 25