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An in-depth review of glycogen metabolism and gluconeogenesis, including the enzymes involved, their functions, and the regulatory mechanisms. Topics covered include glycogen storage in liver and muscles, identical pathways for synthesis and degradation, key enzymes such as phosphoglucomutase, udpglc pyrophosphorylase, glycogen synthase, glycogen phosphorylase, and glucose 6-phosphatase, and the role of glucagon and epinephrine in regulating glycogen metabolism in the liver and skeletal muscles.
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Glycogen is stored primarily in the: - ANSWERS: liver and skeletal muscles Pathway for synthesis and degradation are identical. True or False - ANSWERS: True Enzymes used for Glycogen synthesis - ANSWERS: Phosphoglucomutase, UDPGlc pyrophosphorylase, and Glycogen synthase Glycogen synthesis - UDPGlc pyrophosphorylase: - ANSWERS: Glucose 1-P + UTP → UDPGlc Glycogen synthesis - Phosphoglucomutase - ANSWERS: Glucose 6-P is isomerized → Glucose 1-P Glycogen synthesis - Glycogen synthase - ANSWERS: adds UDPGlc → terminal end of glycogen (1→ linkage) Glycogen synthesis - Glycogenin primer is required with - ANSWERS: Glycogen synthase Glycogen degradation enzymes - ANSWERS: Glycogen phosphorylase, and Glucose 6-Phosphatase Which enzyme is required to de-phosphorylate glucose to be released from the liver - ANSWERS: Glucose 6-Phosphatase Key difference in liver vs. muscle glycogenolysis - ANSWERS: Glucose 6-Phosphatase: Glucose 6-P → Free Glucose Glucose 6-Phosphatase - ANSWERS: Glucose 6-P → Free Glucose
What enzyme is deficient in the following glycogen storage disease? • von Gierke's disease - ANSWERS: Glucose 6-Phosphatase What gluconeogenic enzyme is absent in muscle, accounting for its inability to use glycogen as a source for blood glucose? - ANSWERS: Glucose 6-Phosphatase In the liver glycogen synthesis and degradation are regulated through two main mechanisms: - ANSWERS: Glucagon activation of GPCR and Epinephrine binds α-adrenergic Glucagon activation of GPCR Activation of Adenylate cyclase → - ANSWERS: increases cAMP Glucagon activation of GPCR cAMP activates Protein kinase A (PKA) → - ANSWERS: phosphorylates phosphorylase kinase Glucagon activation of GPCR phosphorylated phosphorylase kinase → - ANSWERS: phosphorylates glycogen phosphorylase→ glycogen degradation Glucagon activation of GPCR cAMP activates PKA → - ANSWERS: phosphorylates glycogen synthase →inactivates Glucagon activation of GPCR - ANSWERS: Activation of Adenylate cyclase, cAMP activates Protein kinase A (PKA), and cAMP activates PKA Epinephrine binds α-adrenergic - ANSWERS: Cleavage of PIP, IP3, DAG Epinephrine binds α-adrenergic Cleavage of PIP → - ANSWERS: IP3 and DAG
Epinephrine binds α-adrenergic IP3 → - ANSWERS: stimulates Ca2+ release from ER Epinephrine binds α-adrenergic ▪ Ca2+ stimulates two responses - ANSWERS: Ca2+ calmodulin → activates phosphorylase kinase and calmodulin dependent kinase Epinephrine binds α-adrenergic Ca2+ calmodulin → activates phosphorylase kinase - ANSWERS: phosphorylate glycogen phosphorylase → glycogen degradation Epinephrine binds α-adrenergic Ca2+ calmodulin dependent kinase → - ANSWERS: phosphorylates glycogen synthase →inactivates Epinephrine binds α-adrenergic DAG → - ANSWERS: activates protein kinase C (PKC) In the skeletal muscle glycogen synthesis and degradation are regulated through three main mechanisms: - ANSWERS: Epinephrine activation of GPCR, Ca2+ mediated muscle contraction, and Elevated AMP ____________ is NOT impacted by GLUCAGON - ANSWERS: skeletal muscle skeletal muscle glycogen synthesis and degradation are regulated through Elevated AMP - ANSWERS: allosterically activates glycogen phosphorylase skeletal muscle glycogen synthesis and degradation are regulated through
Ca2+ mediated muscle contraction - ANSWERS: Ca2+ calmodulin ▪ → activates phosphorylase kinase skeletal muscle glycogen synthesis and degradation are regulated through Epinephrine activation of GPCR - ANSWERS: Activation of Adenylate cyclase, cAMP activates Protein kinase A (PKA), and cAMP activates PKA skeletal muscle glycogen synthesis and degradation are regulated through Ca2+ mediated muscle contraction Ca2+ calmodulin ▪ → activates phosphorylase kinase → - ANSWERS: phosphorylates glycogen phosphorylase→ glycogen degradation skeletal muscle glycogen synthesis and degradation are regulated through Epinephrine activation of GPCR cAMP activates PKA → - ANSWERS: phosphorylates glycogen synthase →inactivates skeletal muscle glycogen synthesis and degradation are regulated through Epinephrine activation of GPCR cAMP activates Protein kinase A (PKA) → - ANSWERS: phosphorylates phosphorylase kinase skeletal muscle glycogen synthesis and degradation are regulated through Epinephrine activation of GPCR cAMP activates Protein kinase A (PKA) → phosphorylates phosphorylase kinase→ - ANSWERS: phosphorylates glycogen phosphorylase→ glycogen degradation skeletal muscle glycogen synthesis and degradation are regulated through Epinephrine activation of GPCR
Activation of Adenylate cyclase → - ANSWERS: increases cAMP BOTH ____________________ and ___________________ provide glucose for Maintaining blood glucose - ANSWERS: glycogenolysis and GNG Substrates of gluconeogenesis - ANSWERS: glycerol, lactate, amino acids Substrates of gluconeogenesis lactate dredominantly - ANSWERS: from the Cori Cycle Substrates of gluconeogenesis Glycerol is predominantly - ANSWERS: released during lypolysis Substrates of gluconeogenesis - ANSWERS: primarily alanine from skeletal muscle and Lactate and alanine are shuttle from - ANSWERS: skeletal muscle ______ and ______ are not substrates of gluconeogenesis - ANSWERS: fatty acids and ketogenic amino acids As pertains to gluconeogenesis- fatty acids and ketogenic amino acids - ANSWERS: These are metabolized to acetyl-CoA and are fully oxidized in the TCA cycle There are 4 steps that are unique to gluconeogenesis. These steps overcome the 3 regulatory steps in glycolysis. - ANSWERS: Pyruvate carboxylase (PC; mitochondrial enzyme): carboxylates pyruvate to OAA Phosphoenol pyruvate carboxykinase (PEPCK; cytosolic enzyme) Fructose 1,6-bisphosphatase (FBP-1; cytosolic)
Glucose 6-phosphatase Glucose 6-phosphatase - ANSWERS: dephosphorylates glucose 6-phosphate to free glucose that can be released from the liver This enzyme is used by both gluconeogenesis and glycogenolysis - ANSWERS: Glucose 6-phosphatase What gluconeogenic enzyme is absent in muscle, accounting for its inability to use glycogen as a source for blood glucose? - ANSWERS: Glucose 6-phosphatase Gluconeogenesis In the FASTED state the enzyme has phosphatase activity - ANSWERS: Fructose 2, 6-bisphosphatase Gluconeogenesis in the fasted state Fructose 2, 6-bisphosphatase - ANSWERS: Generates fructose 6-phosphate FBP-2 is phosphorylated and the phosphatase portion is active; kinase portion is inactive Gluconeogenesis in the fasted state When FBP-2 is phosphorylated and the phosphatase portion is __________; kinase portion is _________ - ANSWERS: active and inactive Pyruvate carboxylase and PEPCK are both required to overcome the glycolytic reaction catalyzed by _____________________ - ANSWERS: pyruvate kinase
________________ and _______________ are both required to overcome the glycolytic reaction catalyzed by pyruvate kinase - ANSWERS: Pyruvate carboxylase and PEPCK Fructose 1,6-bisphosphatase (FBP-1; cytosolic): - ANSWERS: converts fructose 1,6-bisphosphate to fructose 6-phosphate Fructose 1,6-bisphosphatase (FBP-1; cytosolic): Activity is_______________ by AMP and fructose 2,6- bisphosphatase - ANSWERS: inhibiited Enzyme overcomes the irreversible glycolytic reaction catalyzed by _______________ - ANSWERS: phosphofructokinase- Fructose 2,6-bisphosphatase (FBP-2) is active and reduces the amount of __________ as a means of reducing the allosteric activation of __________ which enhances the reverse reaction catalyzed by _________________ - ANSWERS: fructose 2,6 bisphosphate, PFK1, and fructose 1,6-bisphosphatase FBP-2 is a bifunctional enzyme In the FED state the enzyme has kinase activity and is termed - ANSWERS: Phosphofructokinase-2 (PFK2) FBP-2 is a bifunctional enzyme In the FED state the enzyme has kinase activity and is termed Phosphofructokinase-2 (PFK2) Generates _____________ that allosterically activates _____ - ANSWERS: fructose 2,6-bisphosphate and PFK- FBP-2 is a bifunctional enzyme In the FED state the enzyme has kinase activity and is termed Phosphofructokinase-2 (PFK2)
PFK-2 is dephosphorylated _______________and the __________ portion is active and the ____________ portion is ____________ - ANSWERS: kinase, active, phosphatase, inactive PFK-2 is dephosphorylated and the kinase portion is active and the phosphatase portion is inactive - ANSWERS: OAA is reduced to malate and malate can leave the mitochondria ▪ Requires acetyl-CoA for allosteric activation ▪ Requires biotin as a cofactor Phosphoenol pyruvate carboxykinase (PEPCK; cytosolic enzyme): converts cytosolic OAA → phosphoenol pyruvate - ANSWERS: Transcription of this enzyme is enhanced by high levels of cortisol Phosphoenol pyruvate carboxykinase (PEPCK; cytosolic enzyme): converts - ANSWERS: cytosolic OAA → phosphoenol pyruvate Pyruvate carboxylase (PC; mitochondrial enzyme): - ANSWERS: carboxylates pyruvate to OAA