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METABOLIZAM UGLJIKOHIDRATA METABOLIČKI PUTEVI Shematski prikaz katabolizma Složeni metaboliti kao što su ugljikohidrati, masti i proteini razgrađuju se prvo do na monomerne jedinice (većinom glukozu, aminokiseline, masne kiseline i glicerol), a zatim do acetil-CoA koji ulazi u ciklus limunske kiseline. Lactose intolerance Fate of Galactose and Fructose BLOOD fructose fructose glucose galactose glucose galactose LIVER Absorption of glucose from the blood: Facilitated diffusion Glucose Transporters (GLUT) GLUT-1 through GLUT-5 TRANSPORT GLUKOZE U STANICU 1. OLAKŠANI TRANSPORT - uz transportere GLUT1-5, čiju aktivnost povećava INZULIN - npr. GLUT-4 je prisutan u adipoznom tkivu i skeletnim mišićima, a GLUT-1 u eritrocitima - konc. Glu izvan stanice je povećana Glucose Uptake by Muscles and Fat Cells TRANSPORT GLUKOZE U STANICU 2. KOTRANSPORT -“protiv” koncentracijskog gradijenta - uz istovremeni transport Na+ -odvija se u intestinalnim epitelnim stanicama, te u bubrežnim tubulima Metabolički putevi ugljikohidrata • GLIKOLIZA • GLUKONEOGENEZA • CIKLUS PENZOZA FOSFATA – oksidativni put – neoksidativni put • GLIKOGENOLIZA • GLIKOGENEZA GLIKOLIZA Oksidativna razgradnja glukoze-6-fosfata do piruvata GLIKOLIZA • AEROBNA GLIKOLIZA (glukoza-piruvat-acetil CoA- CLK-RL-ATP) • ANAEROBNA GLIKOLIZA (glukoza-piruvat-laktat) Heksokinaza Fruktokinaza Glukoza-6-fosfataza Fruktoza-1,6-bisfosfataza Pregled ključnih reakcija i enzima glikolize i glukoneogeneze Piruvat kinaza Fosfoenol-piruvat karboksikinaza Piruvat-karboksilaza AEROBIC ANAEROBIC glucose glucose Minor Source of ATP ONLY Source of ATP 2 pyruvate 2 pyruvate Minor Source of ATP 2 acetyl CoA TCA Major Source of ATP 2 lactate Zašto nastaje laktat Why Lactate is Formed? glyceraldehyde-3-P dehydrogenase 1,3-bisphosphoglycerate glyceraldehyde-3-phosphate ADP ATP 3-phosphoglycerate + NAD ETS anaerobic U Under anaerobnim (aerobic conditions uvjetima ne the djeluje conditions ETS only) respiratorni lanac doesn’t work NADH + H+ 2-phosphoglycerate phosphoenolpyruvate ADP ATP pyruvate lactate lactate dehydrogenase Cori Cycle 3 2 4 1 Exercising muscles also generate lactate IV. CARBOHYDRATE METABOLISM A. Digestion and absorption B. Glycolysis 1. General characteristics 2. Individual reactions 3. Lactic dehydrogenase 4. Pyruvate oxidation 5. Energetics Pyruvate Oxidation H3C O pyruvate dehydrogenase O H3C COO CoASH NAD+ SCoA + CO2 NADH + H+ Pyruvate Dehydrogenase is a multienzyme complex (like alpha ketoglutarate dehydrogenase) Consists of 3 enzymes Requires 5 coenzymes: TPP, coenzyme A, lipoic acid, FAD and NAD + Regulation of Pyruvate Dehydrogenase glucose Stimulated by ADP Inhibited by: ATP, acetyl CoA and excess fatty acids pyruvate CYTOSOL ATP pyruvate carboxylase pyruvate CO2 pyruvate dehydrogenase acetyl CoA ADP + Pi Stimulated by Acetyl CoA OAA TCA citrate MITOCHONDRIA Fatty Acids Energetics of Glycolysis AEROBIC ANAEROBIC glucose glucose 2 ATP - 2 ATP 2 NADH ETS 2 ATP 6 ATP 4 ATP 4 ATP(SLP) -2 ATP NAD+ 4 ATP 4 ATP NADH 2 pyruvate 2 pyruvate ETS 2 NADH 6 ATP 2 ATP NET 2 acetyl CoA TCA 12 ATP x 2 = 24 ATP NET 38 ATP 2 lactate GLUKONEOGENEZA SINTEZA GLUKOZE IZ SPOJEVA KOJI NISU UGLJIKOHIDRATI 2. Fosfoenol-piruvat karboksikinaza 1. Piruvat karboksilaza 2 KLJUČNA ENZIMA: • PIRUVATKARBOKSILAZA • PEP (FOSFOENOLPIRUVAT) KARBOKSIKINAZA Cori Cycle 3 2 4 1 Exercising muscles also generate lactate CIKLUS PENTOZA FOSFATA (PPP,CPF) Overview of the Pentose Phosphate Pathway fatty acid synthesis 2 NADP+ glucose 2 NADPH steroid synthesis glutathione reduction OXIDATIVE PHASE glucose-6- P Oxidatively decarboxylates glucose-6-P to ribulose-5-P ribulose-5- P + CO2 INTERCONVERSION PHASE Converts ribulose-5-P back to glyceraldehyde-3- P glucose-6-P METABOLIZAM GLIKOGENA 1. GLIKOGENEZA SINTEZA GLIKOGENA (UTP) 2 Pi GLIKOGENOLIZA RAZGRADNJA GLIKOGENA Glycogenolysis H2 O The Fate of Glucose-6-phosphate Pi glucose Blood (glucose-6-phosphatase) phosphoglucomutase Glucose-1- P H2 O LIVER Glucose-6- P MUSCLES Glycolysis in muscles for energy Summary of Glycogen Metabolism (immediately after a meal) (2 to 3 hours following a meal) * * Glucose-6-phosphatase No glucose-6-phosphatase Glucagon binds to receptors in the LIVER ONLY. Epinephrine binds to receptors primarily in the MUSCLES but also in LIVER. GTP displaces GDP on the a subunit of the G protein GTP on the a subunit is hydrolyzed