SM162 Intermediary Metabolism I Flashcards
Catabolism vs. Anabolism
Catabolism: breakdown, extract energy
Anabolism: synthesis
3 cellular fates of glucose
Glycolysis
Glycogenesis
Pentose phosphate pathway
What happens to glucose when it enters the cell? Why? What enzyme does this?
Gets phosphorylated
Traps the molecule within the cell
Hexokinase (yield glucose-6-phosphate)
Rate-limiting enzyme in glycolysis
Phosphofructokinase-1 (PFK-1)
This is the irreversible committment step for entry of G6P into glycolysis
Overall glycolysis reaction
Glucose + 2 NAD + 2 Pi + 2 ADP –>
2 pyruvate + 2 NADH + 4 H+ + 2 ATP + 2 H2O
Glycolysis pathway
Glyceraldehyde 3-phosphate dehydrogenase actions
Oxidizes glyceraldehyde-3-P (G3P) and transfers electrons to NAD to form NADH
Glycolysis steps that directly generate ATP (name the enzymes)
Phosphoglycerate kinase and pyruvate kinase
Regeneration of NAD
Needed to continue glycolysis
Anaerobic: lactic acid pathway - convert pyruvate to lactate and NAD (lactate dehydrogenase)
Aerobic: NAD is regenerated in the TCA cycle
Aerobic vs. anaerobic glycolysis yield
Aerobic: 30-32 ATP/glucose
Anaerobic: 2 ATP/glucose
3 key regulation steps in glycolysis
1) hexokinase, 2) PFK-1, 3) pyruvate kinase
Hexokinase regulation
Inhibited by G6P (its product)
Low Km in most tissues except liver (high Km ensures G6P is available for energy storage)
PFK-1 regulation
Allosteric regulation
Inhibitory: ATP and citrate
Stimulatory: AMP and fructose-2,6-bisP
Fructose 2,6-bisP, PFK-2, and PFK-1 regulation
F2,6-bisP regulates PFK-1
Not generated in glycolysis, instead controlled by the bifunctional kinase/phosphatase PFK-2 that is in turn under the control of PKA
Liver: fasting causes glucagon release and cAMP-dependent PKA activity, which phosphorylates PFK-2, leading to less F2,6-bisP and less glycolysis
Heart: adrenergic stimulus or more AMP -> more F2,6-bisP -> more glycolysis
Pyruvate kinase regulation
Tissue-specific isoenzymes including R (red cells), L (liver), M1/M2 (muscle)
L form has allosteric sites. Activation: fructose 1,6-bisP, inhibition: ATP. Can also be non-allosterically blocked by PKA phosphorylation
Pentose phosphate pathway
Produces ribose-5-P to synthesize nucleotides
Generates NADPH from NADP for fatty acid and steroid biosynthesis and to prevent oxidative damage through reduced glutathione in RBCs
Converts pentoses to hexoses, which go on to become nucleotides or reenter glycolysis
High activity in the adrenals, liver, and mammary gland
Glucose 6-phosphate dehydrogenase: pathway, importance, regulation, chromosome type
Part of the PPP
Rate-limiting step
Regulated by NADP/NADPH ratio
X-linked gene
Glucose 6-phosphate dehydrogenase deficiency
Inherited deficiency leads to hemolytic anemia in the setting of oxidizing drugs or diets
Oxidizing drugs/diet includes fava beans, sulfa antibiotics, Tb drugs, and malaria drugs
Most important in the RBCs
Gluconeogenesis starting materals
Can use glycerol, alpha-keto acids, or lactate
Gluconeogenesis: role during fasting, locations in the body
Sole source of glucose
Liver, kidneys, intestinal epithelium
Gluconeogenesis: differences from glycolysis
Differs at the 3 irreversible steps of glycolysis (hexokinase, PFK-1, pyruvate kinase)
Gluconeogenesis: role of ATP and citrate
Products of glycolysis, indicate that energy production is high
Feedback and shut off glycolysis
Overall gluconeogenesis reaction
2 Pyruvate + 6 ATP + 2NADH + 2H+ + 2H2Oàglucose + 6 ADP + 6 Pi + 2 NAD+
Fructose 1,6 bisphosphatase: pathway, reaction, regulation
Gluconeogenesis
Removes the phosphate group from carbon 1 of fructose 1,6-bisphosphate
Activated by citrate, inhibited by fructose 2,6-bis-P
Glucose-6-phosphatase: pathway, reaction
Gluconeogenesis
Converts glucose-6-P to glucose
Pyruvate carboxylase and PEP carboxykinase: pathway, reactions, regulation
Gluconeogenesis
Carry out successive reactions to turn pyruvate into oxaloacetate and then phosphoenolpyruvate (PEP)
Pyruvate carboxylase is activated by acetyl CoA
Gluconeogenesis pathway
Glycogenesis: describe steps, which is the most important regulation point?
G6P converted to G1P by phosphoglucomutase
G1P reacts with UTP to form UDP-glucose
UDP-glucose gets add in an alpha-1,4 linkage to glycogen polymer by glycogen synthase (regulated step)
When chains reach ~11 residues in length, alpha-1,4 glucose oligos are removed by branching enzyme and reattahced to make alpha-1,6 bonds
How many ATP are used in glycogenesis for each molecule of glucose?
2
What happens to glycogen if you have no branching enzyme?
Long glucose polymers with no branches and lots of alpha-1,4 linkages
Continue with glycogenolysis
Continue with glycogenolysis
