Lecture Exam 1 Flashcards
(39 cards)
What is a beta-granule? What protein is at the core?
-Beta Granule: cytosolic granules that vary in size, structure, and subcellular location that appear as electron-dense particles
-Glycogenin is the protein at the core
What forms the initial primer for glycogen?
Glycogenin
What enzymes are involved in building glycogen and what are their roles?
-Phosphoglucomutase: converts glucose-6-phosphate into glucose-1-phosphate
-UDP-glucose pyrophosphorylase: converts glucose 1-phosphate to UDP-glucose
-Glycogenin: the primer on which new chains are assembled and the enzyme that catalyzes the assembly of glycogen
-Glycogen Synthase: catalyzes the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branched glycogen molecule, forming an alpha 1-4 linkage
-turned on when dephosphorylated by PP1; turned off when phosphorylated
-Glycogen Branching enzyme: catalyzes the formation of tha alpha 1-6 bonds found at the branch points of glycogen
What factors/hormones regulate the synthesis of glycogen? How does this differ between the liver and the muscle?
-Liver:
-High Blood Sugar: insulin is high; glycogen synthesis increases; glycogen breakdown decreases; increase PP1; decrease GSK-3
-Low Blood Sugar: decrease Glycogen Synthase; decrease glycogen synthesis; increase FBPase-2
-Muscle:
-Insulin: increase glycogen synthesis
-Glucagon: increases release of glucose (primarily acts on liver)
-Epinephrine: activates glycogenolysis to provide ATP
-The liver will shut down glycolysis if they dont need energy, but the muscle will not
What enzymes are involved in breaking down glycogen? What are their roles?
-Glycogen Phosphorylase: catalyzes phosphorylytic cleavage at the nonreducing ends of glycogen chains
-Debranching Enzyme: transfers branches onto main chains and releases the residue at the alpha 1-6 branch as free glucose
-Phosphoglucomutase: converts glucose-1-phosphate into glucose-6-phosphate
What happens to glucose released from glycogen in muscle vs. liver?
What factors/hormones regulate glycogen break down? How does this differ between the liver and the muscle?
How do CKII and GSK3 cooperate to activate glycogen synthase?
-GSK3 cannot phosphorylate glycogen synthase until casein kinase II has phosphorylated the glycogen synthase on a nearby residue (a priming event)
What is phosphoprotein phosphatase 1 (PP1) and what is its role in regulating glycogen metabolism?
-PP1: removes phosphoryl groups from phosphorylase a, converting it to the less active form, phosphorylase b; also inactivates Glycogen Synthase b by adding a phosphate to glycogen synthase a
What does the pyruvate dehydrogenase complex (PDH) do? Where is it located?
-PDH oxidizes pyruvate to acetyl-CoA and CO2
-It is located in the mitochondrial matrix
What coenzymes are used by the PDH?
-Thiamine pyrophosphate (TPP)
-Lipoate
-Coenzyme A (CoA, CoA-SH)
-Flavin adenine dinucleotide (FAD)
-Nicotinamide adenine dinucleotide (NAD)
What are the roles of the E1, E2, and E3 enzymes of the PDH?
-E1 enzyme: pyruvate dehydrogenase, E1, with bound TPP catalyzes:
step 1: decarboxylation of pyruvate to the hydroethyl derivate rate-limiting step step 2: oxidation of the hydroethyl derivate to an acetyl group electrons and the acetyl group are transferred from TPP to the lipoyllysyl group of E2
-E2 enzyme: dihydrolipoyl transacetylace catalyzes Step 3: esterification of the acetyl moiety to one of the lipoyl-SH groups, followed by transesterification to CoA to form acetyl-CoA
-E3 enzyme: catalyzes Step 4: electron transfer to regenerate the oxidized form of the lipoyllysyl group; Step 5:electron transfer to regenerate the oxidized FAD cofactor, forming NADH
What does the citric acid cycle do? What purpose does it play in energy generation?
-Citric Acid Cycle: a hub of metabolisim, with catabolic pathways leading in and anabolic pathways leading out. Oxidation of acetyl groups to CO2; nearly universal pathway that generates NADH, FADH2, and one GTP
What are the irreversible steps of the citric acid cycle?
-Step 1: Formation of Citrate
-Step 3: Oxidation of Isocitrate to alpha Ketoglutarate and CO2
-Step 4: Oxidation of alpha ketoglutarate to succinyl-CoA and CO2
What are the products and outputs from the pathway (in terms of energy and reduced cofactors) per round? Which steps do they come from?
-3 NADH→produced in step 3, 4, and 8 (one per step)
-1 FADH2→produced in step 6
-1 ATP→produced in step 5
Why do the textbook authors use gene duplication and divergent evolution to explain similarities between metabolic pathways (like slide 34)?
-pathways use the same five cofactors, similar multienzyme complexes, and the same enzymatic mechanism
-have homologous E1 and E2, and identical E3
How much ATP is generated from the citric acid cycle alone versus glycolysis?
-The citric acid cycle forms only one ATP per turn, while glycolysis forms 4 ATP (2 net) per turn.
What are antipleuritic reactions? Why is the citric acid cycle called amphibolic?
-Antipleuritic reactions: Chemical reactions that replenish intermediates
-Amphibolic Pathway: one that serves in both catabolic and anabolic processes
-The Citric Acid Cycle is an amphibolic pathway because it has both catabolic and anabolic pathways
What biomolecule anabolic pathways are fed by components of the citric acid cycle?
-Fatty acids and sterols are fed by citrate
-alpha ketoglutarate feeds into glutamate, which feeds purines and different amino acids
-Succinyl-CoA feeds into porphryins and heme
-Oxaloacetate feeds into Asparate and Asparigine to make pyrimadines
How does pyruvate carboxylase help when acetyl-CoA levels build up?
-Pyruvate Carboxylase: catalyzes the reversible carboxylation of pyruvate by HCO3- to form oxaloacetate
-it is allosterically activated by acetyl-CoA
What are the main points of regulation from the PDH through the citric acid cycle? What factors inhibit or promote those points?
-Main Points of Regulation:
-PDH Complex
-Citrate Synthase
-isocitrate dehydrogenase complex
-alpha-ketoglutarate dehydrogenase complex
-Inhibiting or Promoting:
-Inhibiting PDH: ATP, acetyl-CoA,NADH, fatty acids
-Activating PDH: AMP, CoA, NAD+, Ca2+
-Inhibiting Citrate Synthase: NADH, succinyl-CoA, citrate, ATP
-Activating Citrate Synthase: ADP
-Inhibiting isocitrate dehydrogenase complex: ATP
-Activating isocitrate dehydrogenase complex: Ca2+, ADP
-Inhibiting alpha-ketoglutarate: succinyl-CoA, NADH
-Activating alpha-ketoglutarate dehydrogenase complex: Ca2+
What does beta oxidation do? What are the products of the process? Where does it occur?
-Beta Oxidation: oxidation of the fatty acid group at the C-3, or Beta position-hence the name
-Products: 8 acetyl-CoA, 7 FADH2, 7 NADH, 7H+
-Occurs after the carboxyl group at C-1 is activated by attachment to coenzyme A
How are dietary fats absorbed? What happens to triacylglycerols in the gut and where do the components go when they get absorbed?
-Dietary Fats are absorbed in the small intestine
-Triacylglycerols are degraded by intestinal lipases and the components go into chylomicrons, which travel through the body until they convert to fatty acids and monoacylglycerols
What is a chylomicron? Where is it formed? Where does it go?
-Chylomicrons: particles consisting of triacylglycerols, cholesterol, and apolipoproteins
-They are formed in intestinal cells
-They move through the lymphatic system and bloodstream to get to the tissues
