Glycogen metabolism and pentose phosphate pathway Flashcards
What is the pentose phosphate pathway?
Alternate glucose metabolic pathway occurring in cytosol.
Mostly occurs in cells that synthesize a lot of lipids or are subject to oxidative damage.
What are the phases of the PPP?
Oxidative and non-oxidative
What are the products of the PPP?
NADPH and ribose-5-phosphate
What are the steps in the oxidative phase?
1) Glucose-6-phosphate oxidized to 6-phospho-D-glucono-delta-lactone
2) 6-phospho-D-glucono-delta-lactone to 6-phospho-D-gluconate
3) 6-Phospho-D-gluconate to 3-keto-6-phospho-D-gluconate
4) 3-keto-6-phospho-D-gluconate to D-Ribulose-5-phosphate
What happens in the nonoxidative phase?
Produces important intermediates for nucleotide biosynthesis and glycolysis.
Ribose-5-phosphate
Glyceraldehyde-3-phosphate
Fructose-5-phosphate
How is the PPP regulated? What is the main enzyme?
Regulation is necessary to meet cell’s needs for ribose-5-phosphate and NADPH
If cell requires more NADPH than Ribose-5-phosphate, products of nonoxidative phase can be shuttled into glycolysis
Main enzyme is Glucose-6-P dehydrogenase. Inhibited by NADPH; stimulated by glucose-6-P and oxidized glutathione (GSSG)
What are other important sugars in biological metabolism?
Fructose, galactose, mannose
How is fructose metabolized?
Can enter glycolysis in two ways:
1) Directly convert to Fructose-6-phosphate (THIS IS RARE)
2) Convert to fructose-1-phosphate, then DHAP (OCCURS MOST OF THE TIME). This skips regulatory enzymes (hexokinase and fructose-1,6-bisphosphatase)
Fructose also glycosylates A1C protein
How is galactose metabolized?
Galactose -> UDP-glucose -> can then enter glycogenolysis
What is glycogenesis? When does it occur?
Synthesis of glycogen (storage form of glucose)
Occurs when glucose levels are high
What are the three reaction sets involved in glycogenesis?
1) glucose -> glucose-1-phosphate, via phosphoglucomutase
2) G1P -> UDP glucose, via UDP-glucose phosphorylase
3) UDP-glucose -> glycogen
requires 2 enzymes:
- Glycogen synthase to grow the chain
- Branching enzyme to create linkages for branches
What are the steps in glycogen synthesis, starting from primer formation?
Primer formation:
Glycogenin polymerizes 4 UDP-glucose molecules to itself in alpha(1,4) linkages. UDP is lost during this process. Creates a line of 4 glucose bonded to glycogenin.
1) Glycogen synthase adds more glucoses in alpha(1,4) links via UDP-glucose
2) After at least 11 residues are added, branching enzyme removes 7 residues and transfers them to another glucose in alpha(1,6) link. This increases glycogen solubility.
What is glycogenolysis? When does it occur?
Breakdown of glycogen, initated hours after meal and stimulated by low blood glucose.
What enzymes does glycogenolysis require?
1) Glycogen phosphorylase, to hydrolyze 1,4 links
2) Debranching enzyme, to hydrolyze 1,6 links
What are the steps of glycogenolysis?
1) Glycogen phosphorylase removes glucoses from non-reducing ends up to four glucoses of a branch point. Creates a “limit dextrin”
2) Debranching enzymes remove outer 3 glucoses from branch site and transfer them to nearby non-reducing end of glucose. Then go back for last glucose and remove it.
Yields glucose-1-phosphate and glucose, which can be used in glycolysis or released into blood.
