Glucose is generated by Dietary Carbohydrates

Starch + glycogen: main source of glucose Mainly brocken down by α-amylase (cleaves α 1->4)

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Glycolysis is an Energy-Conversion Pathway in Many Organisms

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Summary of glycolysis

-> 10 reaction steps -> 1 x C-6 (glucose) converted into 2x C-3 (pyruvate) -> oxidation of glucose -> 2 NADH generated -> 2 ATPs used + 4 ATPs generated -> pay off: 2 ATPs

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Glucose Metabolism Under Aerobic and Anaerobic Conditions

Final Electron-acceptor: Aerobic -> O2

Anaerobic -> Pyruvate

Cytosol

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Why do we need to produce lactate or ethanol (yeast) anaerobic and not stop at pyruvate?

Gycolysis: Oxidation reaction generates NADH from NAD+

Under anaerobic conditions: reaction from Pyruvate to Lactate or Ethanol -> regenerate NAD+

Under aerobic conditions: regeneration of NAD+ happens in respiratory chain (mitochondria) -> via 2 different shuttles

-> Regeneration of NAD+

Uridine diphosphate galactose Galactose toxic if transferase is missing

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Regulation of glycolysis in the muscle

ATP inhibits all 3 enzymes Need for ATP (high AMP) activates PFK

-> ATP based regulation

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Regulation of glycolysis in the liver

Regulation by: -> ATP -> glucose level in blood -> need for building bocks for biosynthesis

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Regulation of glycolysis in the liver

Proteins responsible for uptake of glucose into the cell -> regulate blood glucose level Uptake of glucose (tranporters) -> metabolism of glucose

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• Brain and blood cells depend on glucose -> 160g/day (mainly for the brain)

• Glucose in the blood: 20g, as glycogen: 190g

• Starvation > 1day other metabolites for energy!

-> Gluconeogenesis pathway: • Takes place in liver (and kidneys) • Important to maintain blood glucose level

• Major precursors: glycerol, amino acids,

lactic acid

• Specific enzymes in addition to glycolysis (for the irreversible steps in glycosis)

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Synthesis of glucose from non-carbohydrate precursors: -> gluconeogenesis

Triacylglycerols (Lipids) taken up by diet -> brocken down to fatty acids and glycerol

cannot by converted to glucose

glucose

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Glycolysis <-> gluconeogenesis

Glycolysis: in the cytosol Gluconeogenesis: major part in cytosol -> 1st step in mitochondria -> shuttle

Reverse reaction of glycolysis thermodynamically not favorable !!!

Biotin: prosthetic group -> carrier for CO2

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Synthesis of glucose from non-carbohydrate precursors: -> gluconeogenesis

Pyruvate (end product of glycolysis) -> under aerobic conditions -> shuttle into Mitochondria -> converted into acetyl-CoA -> citric acid cycle

Gluconeogenesis -> start with pyruvate in mitochondria 1st Step: convertion to oxaloacetate -> malate/oxaloacetate shuttle glycolysis

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Synthesis of glucose from non-carbohydrate precursors: -> gluconeogenesis

Free glucose is important control point -> pathway ends mostly with glucose-6-P -> finished just if glucose is needed (in blood) -> advantage of stopping at glucose-6-P -> trapped in the cell (cannot shuttle outside)

Last step of gluconeogenesis: in ER lumen -> glucose shuttled back to cytosol -> leaves cell

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Synthesis of other saccharides through gluconeogenesis

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Reciprocal regulation of glycolysis & gluconeogenesis

• Pathways not active at same time

• Regulated by products of reaction and precursors (allostery)

• Regulated by hormones: glucagon & insulin, through F-2,6-BP

• Regulated at the transcriptional level of genes

In the liver: aim is to maintain blood glucose level

glucagon insulin

transcription

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Pathway Integration during a sprint

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