-
reciprocal regulation of glycolysis/gluconeogeneis
- F 2,6-BP is only in liver
- Side product is not part of either pathway
-
formation of F2,6-BP is controlled by...
- phosphorylation
- PFK2 and F2,6BPase reciprocally regulated by serine phosphorylation
-
Metabolism after meal
- high blood glucose (insulin high)
- dephosphorylated PFK2 is active
- Glycolysis stimulated
-
Metabolism before a meal
- low blood glucose (glucagon high)
- phosphorylated PFK2-inactive
- gluconeogenesis stimulated
-
High glucose levels
- increase F2,6-BP
- increase glycolysis
-
Starvation causes...
- decrease in F2,6-BP
- causes gluconeogenesis
-
PFK regulated by cell's energy charge
- Inhibited by high concentrations of ATP
- ATP binding lowers PFK affinity for F6-P
- AMP reverses inhibitory effect of ATP
-
PFK and citrate
- inhibited by citrate
- high citrate concentrations signal high level of biosynthetic precursors
-
3 steps regulated in glycolysis
- phosphofructokinase
- hexokinase
- pyruvate kinase
-
Futile cycles
- two metabolic pathways run simultaneously in opposite directions and have no overall effect other than wasting energy (net ATP hydrolysis)
- generate heat
-
F1,6BP and AMP
F1,6BP not inhibited by AMP
-
Honeybees (sooo relevant to dentistry!)
- almost no F1,6-BP in flight muscles
- cannot fly in cooler temps than 30 degrees C
-
Hexokinase inhibited by...
G6-P, which acccumulates in the cell as a result of the buildup of F6-P when PFK is inhibited
-
Alanine inhibts or stimulates pyruvate kinase?
- inhibits
- sense levels of biosynthetic precursors
-
Pyruvate Kinase in low blood sugar
phosphorylated, less active
-
Under Anaerobic conditions in the muscle...
- pyruvate and NADH accumulate
- NAD+ must be regenerated for glycolysis to continue
- Cori Cycle
-
PPP
ribose phosphate also produced
-
PPP and glycolysis linked by
transketolase/transaldolase reactions
-
PPP oxidative branch
- G6-P dehydrogenase reaction
- 2 NADPH produced
-
Important enzymes in non-oxidative branch of PPP
- Transketolase
- Transaldolase
-
Transketolase
- 2 carbon unit transfer
- Contains thiamine pyrophosphate (TPP)
- C5+C5 <-> C3+C7
- C5+C4 <-> C3+C6
-
Transaldolase
- 3 carbon unit transfer
- C7+C3 <-> C4+C6
-
Most importatnt regulatory factor of PPP
- level of NADP+
- tightly coupled to its utilization
-
Ratio of NADP+/NADPH
0.014
-
-
Control of non-oxidative branch of PPP
availability of substrates
-
RBCs get ATP from...
glycolysis only!
-
RBCs produce 2,3-BPG from...
1,3-BPG
-
in RBCs, NADPH used to
regenerate reduced glutathione needed to protect against ROS
-
what can produce free radical species?
O2- and H2O2
-
G6-P Dehydrogenase Deficiency
- Can be caused by decreased production of enzyme, decreased catalytic activity, decreased enzyme stability
- exposure to anti-malarial drugs results in incrased cellular production of superoxide and hydrogen peroxide
-
Pyruvate Kinase Deficiency
- ATP from glycolysis used for maintenance of RBC shape and Na/K gradients
- ATP levels low in RBCs
- spherical erythrocytes instead of normal bi-concave disc shaped cells
-
Adenylate system
ADP must be available for glycolysis, citric acid cycle, and Ox/Phos to proceed
-
NAD+ required for...
- glycolysis
- pyruvate dehydrogenase
- Citric acid cycle
- beta-oxidation
- amino acid deamination
-
FAD required for
- Citric acid cycle
- beta oxidation
-
CoA required for
- pyruvate dehydrogenase
- alpha-ketogluterate dehydrogenase
- beta-oxidation
- branched chain ketoacid dehydrogenase
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