Glycogen and the HMP Shunt Flashcards
Glycogen Synthase
Pathway: Glycogen synthesis
Catalyzes transfer of UDP-glucose to the growing glycogen chain, forming an alpha-1,4 glycosidic linkage; UDP is released
Glycogen Phosphorylase
Pathway: Glycogen Breakdown
Removes Glucose-1-Phosphate subunits from glycogen
Phosphorylase Kinase
Pathway: Glycogen breakdown
Phosphorylase is activated by phosphorylation by PKA under the influence of Glucagon; phosphorylase kinase phosphorylates glycogen phosphorylase, activating it to stimulate glycogen breakdown
Protein Phosphatase 1
Pathway: Glycogen breakdown
Protein Phosphatase inactivates phosphorylase under influence of insulin; inactivation of phosphorylase kinase reduces its stimulation of glycogen phosphorylase, therefore inhibiting glycogen breakdown in the fed state
Branching enzyme
Pathway: Glycogen Synthesis
Transfers 6-7 glucose residues from the end of the growing glycogen molecule to an internal site by forming an a-1,6 linkage that produces a branch point
Branching increases the solubility of glycogen and creates a large number of terminal residues which are the sites for further glycogen synthesis as well as future glycogen breakdown
Phosphoglucomutase
Pathway: Glycogen Synthesis & Breakdown
Convert Glucose-6-Phosphate to Glucose-1-Phosphate (glycogen synthesis) and converts G-1-P back to G-6-P (Glycogen breakdown)
Debranching Enzyme
Pathway: Glycogen breakdown
Shifts a block of 3 glycosyl residues to convert the branched glycogen structure into a linear structure, exposing a single glucose residue joined by an a-1,6 glycosidic linkage
Glucosidase
Pathway: Glycogen breakdown
Cleaves the a-1,6 glucose exposed by debranching enzyme to yield a free glucose molecule; this free glucose molecule can be phosphorylated to G-6-P by hexokinase and then enter glycolysis
Where does the HMP shunt pathway occur?
In the cytosol of tissues that undergo fatty acid and steroid synthesis (liver, adipose, mammary gland, adrenal cortex)
Glucose-6-Phosphate Dehydrogenase
Pathway: HMP Shunt
Rate limiting step; converts glucose-6-phosphate to 6-phosphogluconate, generating NADPH
What is the end product of the HMP shunt, and what are its fates?
Ribulose-5-Phosphate and NADPH
NADPH is used to fuel fatty acid synthesis in liver, adipose, adrenal cortex, and mamillary gland
Ribulose-5-Phosphate can be converted to ribose-5-phosphate and then to RNA, DNA, NAD, and FAD; it can also be converted to glycolytic intermediates; finally, it can be recycled to G-6-P to generate more NADPH
G6PD Deficiency
Deficiency of G6PD interferes with NADPH production; NADPH is the reducing agent which maintains glutathione (GSH) in its reduced state; certain compounds such as sulfa and antimalarial drugs and fava beans react with GSH and deplete it; patients with G6PD are unable to regenerate GSH and to guard against reactive oxygen species, causing oxidation of hemoglobin which forms cross-links on the red cell membrane leading to fragility of the membrane and hemolysis
