BICH 411 1st Edition Lecture 13Outline of Previous LectureI. Review for ExamOutline of Current Lecture I. Gluconeogenesis OverviewII. InhibitorsIII. RegulationCurrent LectureGluconeogenesis – forming glucose from metabolites, necessary for the body to maintain its own energy-occurs in the Endoplasmic reticulum, mostly of the liver and kidneys-Diabetes devices use the glucose oxidase reaction to monitor the glucose concentration-gluconeogenesis can use pyruvate, lactate, glycerol, amino acids, and all TCA intermediatesfatty acids can’t be used**note that it’s not just reversed glycolysis! (when one is on, the other is off “reciprocal regulation”-gluconeogenesis uses steps 2 and 4-9 of glycolysis to produce glucose-pyruvate carboxylase and PEP carboxylase replace pyruvate kinase-Fructose-1,6-bisphosphatase replaces phosphofructokinase-Glucose-6-phosphatase replaces hexokinase1: pyruvate + HCO3- + ATPoxaloacetate + ADP + Pi with Pyruvate Carboxylase. Requires ATP and bicarbonate. It is also very biotin dependent (biotin linked with lysine). ***Acetyl-coA is an allosteric activator** Also note that when ATP or acetyl-CoA concentrations are high, pyruvate enters gluconeogenesis. This reaction is the initiation of gluconeogenesis!2: Oxaloacetate + GTP PEP + GDP + CO2 with PEP carboxylase. This is reaction gets its energy from decarboxylation and GTP hydrolysis. 3: Fructose-1,6-Bisphosphate + H2O Fructose-6-Phosphate + Pi with Fructose-1,6-Bisphosphatase. Fructose-1,6-Bisphosphatase is regulated by citrate (positively), and fructose-2,6-bisphosphatase and AMP (negatively). These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.4. Glucose-6-PhosphateGlucose, with Glucose-6-Phosphatase. This involves 3 transport proteins. T1 is responsible for taking Glucose-6-phosphate to the endoplasmic reticulum. T2 exports glucose to the cytosol. T3 exports inorganic phosphates to the cytosol. GLUT 2 transporter takes the glucose out of the endoplasmic reticulum and cell. Important equation: 2 pyruvate + 4ATP + 2 GTP + 2 NADH + 2 H+ + 6 H2O 1 glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+Metformin stimulates the glucose transporters.3-Mercaptopicolinate and hydrazine inhibit the oxaloacetate PEP reaction.Chlorogenic acid inhibits glucose-6-phosphatase. S-3483 does the same. **The liver is very important during exercise! (Cori Cycle)RegulationFor glucose-6-phosphatase, the more substrate, the more enzyme is activated.-the other regulators are allosteric. (acetyl-CoA, AMP, citrate,
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