Glycolysis, TCA Cycle, and Oxidative Phosphorylation Flashcards
GLUT4
Transports glucose into skeletal muscle and adipose tissue
Up-regulated by exposure to insulin
GLUT2
Transports glucose into hepatocytes
Not insulin sensitive
Hexokinase
Pathway: Glycolysis
Catalyzes the first phosphorylation of glucose in most body cells; this reaction is irreversible
Hexokinase is not very selective but has a low Km for sugars
Glucokinase
Pathway: Glycolysis
Catalyzes the first phosphorylation of glucose in hepatocytes and pancreatic B-cells; this reaction is irreversible
Highly selective for glucose but has a high Km; therefore acts as a ‘glucose sensor’ that is highly active when cellular glucose is high, and is less active when cellular glucose is low, allowing glucose efflux from the cell under these conditions
Phosphofructokinase 1 (PFK1)
Pathway: Glycolysis
Catalyzes the phosphorylation of Fructose-6-Phosphate to Fructose-1,6-Bisphosphate
This is the major rate limiting and regulatory step of glycolysis
PFK1 is activated by AMP and F-2,6BP
PFK is inhibited by ATP and citrate
Phosphofructokinase 2 (PFK2)
Pathway: Glycolysis
Converts Fructose-6-Phosphate to Fructose-2,6-Bisphosphate, a strong activator of PFK1
Glyceraldehyde-3-Phosphate Dehydrogenase
Pathway: Glycolysis
Catalyzes the phosphorylation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate
Generates 2 NADH
Phosphoglycerate Kinase
Pathway: Glycolysis
Catalyzes the phosphorylation of 2ADP by 1,3-bisphosphoglycerate, yielding 2 ATP (net ATP is 0)
Pyruvate Kinase
Pathway: Glycolysis
Catalyzes the phosphorylation of 2ADP by 2PEP, yielding 2 ATP (net ATP is 2)
Which cell types undergo anaerobic regeneration of NAD+ during glycolysis?
RBCs
Sperm
Retina
Pyruvate dehydrogenase
Enzymatic link between glycolysis and TCA cycle; converts pyruvate to acetylcoA in the mitochondrial matrix
Requires thiamine (B1), riboflavin (B2), and niacin
PDH is allosterically activated by AMP and NAD+; it is inhibited by ATP and NADH
PDH is active in the fed state (high insulin, dephosphorylated) and is inhibited in the fasting state (high glucagon, phosphorylated)
Citrate Synthase
Pathway: TCA Cycle
Catalyzes the condensation between oxaloacetate and acetylcoA to yield citrate
High citrate reflects high flux through the TCA cycle and feedback inhibits PFK1
Citrate can leave the TCA cycle to form fatty acids via lipogenesis
a-ketoglutarate
Intermediate of the TCA Cycle; production of a-ketoglutarate yields CO2 and NADH
succinyl CoA
Production of succinyl coA from a-ketoglutarate yields a second molecule of CO2 and NADH
Succinate dehydrogenase
Catalyzes the conversion of succinate to fumarate; enzyme-bound FAD is the electron acceptor and electrons from FADH2 are directly passed to coQ in the electron transport system
Fumarase
Pathway: TCA Cycle
Catalyzes the conversion of fumarate to malate
Malate dehydrogenase
Pathway: TCA Cycle
Catalyzes the conversion of malate to oxaloacetate; produces 3rd equivalent of NADH
PGC1a
Molecular mediator of mitochondrial proliferation; being investigated as a drug target to increase oxidative capacity of muscle cells and therefore prevent metabolic diseases
Sirtuins
SIR2 enzyme improves mitochondrial function and may be associated with decreased cellular oxidative damage and increased cellular longevity
Resveratrol found in red wine activates Sirtuins
Lactate Dehydrogenase
Pathway: Gluconeogenesis
Interconverts lactate and pyruvate
Pyruvate carboxylase
Pathway: Gluconeogenesis
Converts pyruvate to oxaloacetate within liver cell mitochondria
Malate dehydrogenase
Pathway: Gluconeogenesis
Occurs as 2 isoforms; cytosolic enzyme converts oxaloacetate to malate, which leaves the mitochondria to enter the cytosol; cytosolic isoform regenerates oxaloacetate from malate
Fructose-1,6-Bisphosphatase
Pathway: Gluconeogenesis
Part of the ‘bifunctional’ enzyme complex (PFK/F-1,6-Bisphosphatase)
High glucagon activates PKA, which phosphorylates PFK-2, inactivating it and leading to reduced production of F-2,6-BP; lower F-2,6-BP levels releases the inhibition of fructose-1,6-bisphosphatase, stimulating gluconeogenesis
Glucose-6-Phosphatase
Pathway: Gluconeogenesis
Catalyzes the conversion of G-6-P to glucose in the final step of gluconeogenesis
G-6-P Phosphatase is found in hepatocytes and kidney cells; these are the only tissues that may export gluconeogenesis-produced glucose into the blood stream
