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Metabolism: Anabolism and Catabolism GTP ? UTP, CTP ? Glycolysis: review & main points Why is glucose such a prominent fuel in all life forms? - glucose is one of the monosaccharides formed from formaldehyde under prebiotic conditions, so it may have been available as a fuel...

Metabolism: Anabolism and Catabolism GTP ? UTP, CTP ? Glycolysis: review & main points Why is glucose such a prominent fuel in all life forms? - glucose is one of the monosaccharides formed from formaldehyde under prebiotic conditions, so it may have been available as a fuel source for primitive biochemical systems - glucose has a low tendency, relative to other monosaccharides, to nonenzymatically glycosylate proteins (Schiff base) Glucose has a strong tendency to exist in the ring formation and, consequently, relatively little tendency to modify proteins. 1  Fate of Glucose: a function of physiological conditions tissues organisms Respiration Glycolysis  2 The first phase of glycolysis ends with the cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP). This readily reversible reaction is catalyzed by the enzyme aldolase. GAP can be processed to pyruvate to yield ATP, whereas DHAP cannot. Enzyme triose phosphate isomerase interconverts GAP and DHAP, allowing the DHAP to be further metabolized 3  Cetose (6) ↔ Cetose (3) + Aldose (3) DG = - 0,3 kcal/mol GAP can be processed to pyruvate to yield ATP, whereas DHAP cannot. The enzyme triose phosphate isomerase interconverts GAP and DHAP, allowing the DHAP to be further metabolized. Triose phosphate isomerase salvages a three-carbon fragment (96%) (4%) DG = + 0,6 kcal/mol Triose phosphate isomerase is the only glycolytic enzyme whose deficiency is lethal 4  The second phase of glycolysis: production of NADH, ATP and pyruvate First phase → no energy has yet been extracted. On the contrary, thus far two molecules of ATP have been invested. Second phase → a series of steps that harvest some of the energy contained in glyceraldehyde 3-phosphate. Substrate-level phosphorylation - is a type of metabolic reaction that results in the formation of ATP or GTP by the direct transfer and donation of a phosphoryl (-PO32-) group to ADP or GDP from a phosphorylated reactive intermediate. 5 Re-oxidação do NADH Anaerobiose: Fermentation An ATP-generating process in which organic compounds act Lactato + NAD+ as both donors and acceptors Piruvato of electrons. Fermentation can take place in the absence of O2 Etanol + CO2 + NAD+ (discovered by Louis Pasteur (1860)). Aerobiose: Respiration An ATP-generating process in Piruvato Acetil-CoA + CO2 + NADH which an inorganic compound (such as molecular oxygen) NADH NAD+ + 2,5 ATP serve as the ultimate electron acceptor. The electron donor can be either an organic compound or a inorganic one. Re-oxidação do NADH em anaerobiose (LDH) Lactato tóxico para as células Estratégia: desvio da carga metabólica 6 Cori cycle LDH LDH Cori cycle - Lactate formed by active muscle is converted into glucose by the liver. This cycle shifts part of the metabolic burden of active muscle to the liver Gluconeogenesis: → Synthesis of glucose from noncarbohydrate precursors - Brain depends on glucose as its primary fuel (red blood cells use only glucose as a fuel) - The daily glucose requirement of the brain → is about 120 g - 160 g of glucose needed daily by the whole body - The amount of glucose present in body fluids → +/- 20 g - Glycogen 190 g (direct glucose reserves are sufficient +/-1 day) - During a longer period of starvation, glucose must be formed from noncarbohydrate sources → Gluconeogenesis 7  Neoglucogénese Ocorrência : citoplasma e mitocôndria Objectivos : Biossíntese de glucose a partir de diferentes precursores Lactato, piruvato, glicerol Aminoácidos glucogénicos Intermediários do ciclo de Krebs Neoglucogénese: necessários desvios Gluconeogenesis  Is not a reversal of Glycolysis 8  1º desvio: 4 etapas para converter piruvato – PEP Enz: piruvato carboxilase + biotina Enz: malato desidrogenase Oxaloacetate leaves the mitochondrion by a specific transport system (not shown) in the form of malate, which is reoxidized to oxaloacetate in the cytosol. Enz: malato desidrogenase Decarboxylation is important: otherwise highly endergonic Enz: fosfoenolpiruvato carboxicinase Equação global do 1º desvio: Piruvato + ATP + GTP → PEP + ADP + GDP + Pi 9  2º desvio: 3º desvio: Equação global: 2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 6 H2O → glucose + 4 ADP+ 2 GDP + 6 Pi + 2H+ ΔGº’= -9kcalmol-1 10 11  12