Glycolysis/Gluconeogenesis/Glycogen Flashcards
Glycolysis steps
Glucose → Glucose-6-phosphate (G6P) via hexokinase (in most tissues) or glucokinase (in liver).
Fructose-6-phosphate to Fructose-1,6-bisphosphate:Enzyme: Phosphofructokinase-1 (PFK-1).
Fructose-1,6-bisphosphate:Splits into GAP (glyceraldehyde-3-phosphate) and DHAP (dihydroxyacetone phosphate).
PEP->Pyruvate
Glucokinase vs. Hexokinase:
Hexokinase (low Km, inhibited by G6P).
Glucokinase (high Km, liver-specific, not inhibited by G6P → allows liver to process high glucose after meals).
Fructose-6-phosphate to Fructose-1,6-bisphosphate: Regulation
Regulation:
Inhibited by ATP (high energy → slows glycolysis).
Activated by AMP (low energy → speeds glycolysis).
Also regulated by Fructose-2,6-bisphosphate (F2,6BP)
Hormonal Regulation of glycolysis
Insulin ↑ glycolysis (↑ F2,6BP in liver).
Glucagon ↓ glycolysis (↓ F2,6BP, promotes gluconeogenesis).
Pyruvate Kinase Regulation:
Activated by F1,6BP (feedforward activation).
Inhibited by glucagon (liver) via phosphorylation.
Why does the liver use glucokinase instead of hexokinase?
Glucokinase has a high Km (low affinity), allowing the liver to phosphorylate glucose only when blood glucose is high (e.g., after a meal). It is not inhibited by G6P, unlike hexokinase.
What is the role of fructose 2,6-bisphosphate (F2,6BP) in glycolysis?
F2,6BP activates PFK-1, promoting glycolysis. Insulin ↑ F2,6BP (fed state); glucagon ↓ F2,6BP (fasting state).
How does ATP regulate glycolysis?
High ATP inhibits PFK-1 (slows glycolysis). Low ATP (high AMP) activates PFK-1 (speeds glycolysis).
What happens to pyruvate under anaerobic conditions?
Converted to lactate (via lactate dehydrogenase) to regenerate NAD⁺ for continued glycolysis.
What are the primary substrates for gluconeogenesis?
Lactate, glycerol (from triglycerides), and glucogenic amino acids (e.g., alanine).
Why can’t acetyl-CoA from fatty acids contribute to gluconeogenesis?
Acetyl-CoA cannot be converted to glucose in humans (no pathway exists). Only glycerol from triglycerides enters gluconeogenesis.
What is the role of the Cori Cycle in gluconeogenesis?
Lactate from muscle glycolysis → transported to liver → converted to glucose via gluconeogenesis → returned to muscle.
Which enzyme converts pyruvate to oxaloacetate (OAA)?
Pyruvate carboxylase (requires ATP and biotin, occurs in mitochondria).
Why is OAA converted to malate during gluconeogenesis?
OAA cannot cross the mitochondrial membrane. Malate acts as a shuttle to transport carbon to the cytoplasm.
What enzyme converts OAA to PEP in the cytoplasm?
PEP carboxykinase (uses GTP, removes CO₂).
How does glucagon regulate gluconeogenesis?
Glucagon ↓ F2,6BP (inhibits glycolysis), ↑ PEP carboxykinase/glucose-6-phosphatase activity, and promotes OAA synthesis.
Why does gluconeogenesis occur primarily in the liver?
Liver has glucose-6-phosphatase, which releases free glucose into the blood.
How does insulin suppress gluconeogenesis?
Insulin ↑ F2,6BP (activates glycolysis), inhibits PEP carboxykinase, and promotes glucose storage as glycogen.
What is the role of fructose-2,6-bisphosphate (F2,6BP)?
F2,6BP is a key regulator:
High levels → activate glycolysis (PFK-1).
Low levels → activate gluconeogenesis (inhibit PFK-1).
Describe glycogen’s structure.
Linear chains: α-1,4 glycosidic bonds between glucose units.
Branch points: α-1,6 glycosidic bonds (every 8–12 glucose units).
Purpose of branching: ↑ solubility and ↑ sites for rapid glucose release.
What enzyme introduces branch points in glycogen?
Branching enzyme (α-1,4:α-1,6 transglycosylase).
How is G6P converted to UDP-glucose?
G6P → Glucose-1-phosphate (G1P) via phosphoglucomutase.
G1P + UTP → UDP-glucose + PPi via UDP-glucose pyrophosphorylase.
What enzyme adds UDP-glucose to the glycogen chain?
Glycogen synthase (forms α-1,4 bonds). Requires a pre-existing glycogen primer (attached to glycogenin).
What enzyme cleaves α-1,4 bonds during glycogenolysis?
Glycogen phosphorylase (releases G1P; requires pyridoxal phosphate/PLP as cofactor).
