Lecture 9 Flashcards
What is the purpose of the glycoxylate pathway? In which organisms is this pathway NOT found?
To convert fats into sugar. It is not found in mammals because they don’t have the proper enzymes.
Describe the glycoxylate pathway
It’s similar to the TCA cycle except there’s not alpha-ketoglutarate or succinyl-CoA. It occurs within the glycoxysome, where fatty acids undergo beta-oxidation to acetyl-CoA. The succinate made can be shuttled over to the mitochondria for the TCA cycle.
What are some enzymes that are common between the TCA cycle and glycoxylate pathway?
Citrate synthase and malate DH.
What are the reactants/products in the glycoxylate pathway, in order?
Fatty acids -> acetyl-CoA -> citrate -> isocitrate -> succinate -> glycoxylate -> acetyl-CoA -> malate -> OAA -> acetyl-CoA again
What are the key enzymes in glycogenolysis?
Glycogen phosphorylase and debranching enzyme
Describe the process of glycogenolysis
Glycogen phosphorylase removes one glucose at a time until four are left. Then, debranching enyzyme cleaves off 3 glucose residues from the alpha 1,6 linkage, leaving one behind, which then gets cleaved off. The 3 glucose residues get moved to the end of the main chain where debranching enzyme can continue its work
Which are the key enzymes of glycogenesis?
Glycogen synthase and branching enzyme
Describe the process of glycogenesis
Glycogenin tethers the first sugar to a Tyr residue to start the chain. UDP donates a sugar, forming UDP-glucose. Then glycogen synthase adds 1 glucose to the non-reducing end, UDP leaves each time. Branching enzyme transfers 6-7 glucose residues to the 6-OH to form an alpha 1,6 linkage.
Describe hexokinase regulation in glycolysis and gluconeogenesis. Where are the two enzyme types found?
HK I is found in the muscle whilst HK IV is in the liver. The latter can directly regulate blood glucose levels. When fructose 6-P is high, HK IV is sequestered in the nucleus. At lower than the Km, HK IV greatly increases in activity. HK I has lower activity than HK IV at normal fasting blood glucose.
What are the Km values of HK I and IV?
HK I = 0.2 mM
HK IV = 10 mM
Which two substrates compete each other in relation to HK IV?
Glucose and fructose 6-P. Glucose activates HK IV to come to the cytosol. Fructose 6-P keeps it sequestered in the nucleus.
Describe the regulation of PFK-1
Allosterically activated by: ADP, AMP, and fructose 2,6-BP
Allosterically inhibited by: ATP and citrate
Describe the regulation of FBPase-1
Allosterically inhibited by AMP and fructose 2,6-BP
Describe fructose 2,6-BP regulation of PFK-1 in more detail
PFK-1 is pretty much inactive without F26BP. PFK-2 synthesizes F26BP and FBPase-2 degrades it, but they’re part of the same protein.
Which hormones regulate F26BP?
Insulin and glucagon, through dephosphorylation and phosphorylation, respectively
Describe the regulation of pyruvate kinase
Allosterically inhibited by: ATP, alanine and other aas, fatty acids, acetyl-CoA
Allosterically activated by: F16BP
Describe the regulation of PEPCK
Inhibited by: insulin
Activated by: glucagon
Transcriptional regulation.
What is the receptor for glucagon in PEPCK regulation? Which other substrates are also regulated by this receptor?
CREB. F16BPase and G6Pase are also regulated by CREB so they can be turned on at the same as PEPCK
Pyruvate carboxylase is activated by which substrate?
Acetyl-CoA
Describe the regulation of the PDH complex
Inhibited by: ATP, acetyl-CoA, NADH, fatty acids
Activated by: AMP, CoA, NAD+, and Ca2+
Which two enzymes in the TCA cycle are activated by Ca2+ as well?
Isocitrate DH and the alpha-ketoglutarate DH complex
Describe the regulation of isocitrate DH
Activated by: Ca2+ , ADP,
Inhibited by: ATP
Describe the regulation of alpha-ketoglutarate DH complex
Activated by Ca2+
Inhibited by: succinyl-CoA and NADH
Describe glycogenolysis, glycogenesis, and glycolysis levels when blood glucose is high
Low, high, high
Describe glycogenolysis, glycogenesis, and glycolysis levels when blood glucose is low
High, low, low
