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Lowest possible blood glucose level
- 1.5 mM, any lower causes coma
- Too high also = coma
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Gluconeogenisis
- Formation of glucose from non-hexose precursors
- Found in all organisms
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Gluconeogenisis Components for Animals
- Lactate, Pyruvate, Glycerol, most Amino Acids
- Takes place in liver/kidney (lesser)
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Gluconeogensis components for Plants
Fats and Proteins (acetyl-CoA from beta oxidation)
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Can fatty acids be a substrate for net glucose production?
- No, going through Kreb's cycle has no net carbon flux
- The process of beta-oxidation and TCA cycle DOES make energy for gluconeogensis though
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Where do carbons in Gluconeogenisis come from?
Amino Acids
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Proteins must be turned to what to be used for Gluconeogenisis
Amino acids, then Pyruvate
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Best way to turn Amino Acids into useful things?
- Transaminiation
- Alanine can become Pyruvate
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Sources of Glycerol for Gluconeogenisis
Adipose cells contain triacylglycerol, lipase cuts off Glycerol tip, liver turns Glycerol into dihydroxyacetone phosphate by phosphorylating and then oxidating
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Gluconeogenisis is similar to what other process
Glycolysis, almost exactly same but backwards and uses other enzymes at "irreversible" steps
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Gluconeogenisis Bypass 1
- Enzyme One: Pyruvate Carboxylase
- Enzyme Two: PEP Carboxykinase
- Occurs in Mitochondria
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Alternate path to PEP
- Pyruvate ->Oxaloacetate -> Malate -> Oxaloacetate -> PEP
- PEP formed outside Mitochondria
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Sources of Lactate
- Pyruvate is turned into lactate via fermentation
- This is called Cori cycle (Glucose to Pyruvate to Lactate to Glucose)
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Liver turns Lactate into
Glucose
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Regulation of Gluconeogenesis/Glycolysis
- Reciprocal Regulation:
- -High Energy: Stimulates gluconeogenesis
- -Low Energy: Stimulates glycolysis
- Major Control Points:
- F-6-P <--> F-1,6,bis-P
- -AMP/ATP ration should push either way
- -Not enough by self
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Phosphofructokinase (PFK-1) (nature and inhibitor)
- Allosteric protein
- Turns Fruc-6-P and ATP into Fruc-1,6-bisP and ADP
- Rate-limiting step in glycolysis
- Inhibited by high levels of ATP (binds active and allosteric site)
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Most Important Regulator of Gluconeogensis/Glycolysis
- Fruc-2,6,-bisP
- -Activates PFK1 (-> Glycolysis)
- -Inhibits FBPase1 (x Gluconeogenisis)
- Tandem Enzymes (PFK2/FBPase2) create and destroy F-2,6-BP respectively
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