Cell Bio: Chapter 11- Fermentation

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What happens after glycolysis?

Under aerobic conditions: pyruvate enters mitochondria and gets turned into acetyl CoA

• NADH donates electrons to ETC

• NAD+ returns to cytosol to participate in glycolysis

Under anaerobic conditions: pyruvate generally does not enter mitochondria and gets turned into ethanol(yeast) or lactate(muscle cell)

• Purpose of fermentation is to turn pyruvate into a mechanism so that NADH can be oxidized (NAD+) and go back to glycolysis

Why is fermentation needed?

• Regenerate NAD+

• In anaerobic conditions if all the finite NAD+ gets turned into NADH, glycolysis would stop

• Fermentation helps oxidate NADH to NAD+ so that glycolysis can continue and ATP can be made via substrate level phosphorylation

Fermentation Reaction In Muscle Cells

Glucose + 2ADP + 2Pi —> 2 lactate + 2ATP

Lactate Oxidation

ΔG°’ = -319.5 kcal/mol (2 lactate = -639 kcal/mol)

• 93% of energy from oxidation of glucose is stored in the lactates

Gluconeogenesis

• Glycolysis in reverse

  • Pyruvate is converted into glucose

The Cori Cycle

• During fermentation, lactate is transported out of the cell and into the bloodstream

• When oxygen returns, the liver oxidizes the lactate into pyruvate and that gets converted into glucose which is either stored or put back into the bloodstream

How many reactions in glycolysis are reversible and irreversible

7 are reversible and 3 are irreversible

Name and explain the 3 irreversible steps that are different in gluconegoensis

Gluconeogenesis: Gluco-6-phosphatase takes the phosphate off glucose-6-phosphate and releases it as a free phosphate to produce glucose (last step)

Glycolysis: hexokinase phosphorylates glucose (first step)

Gluceoneogenesis: Fructose-1,6-bisphosphatase removes a phosphate from fructose-1,6-bisphosphate to make fructose-6-phosphate

Glycolysis: phosphofructokinase 1 phosphorylates the 1st carbon of glucose-6-phosphate to make fructose-6-phosphate

Gluconeogenesis: PEP carboxykinase & pyruvate carboxylase adds a phosphate to make PEP

Glycolysis: Pyruvate Kinase removes phosphate from PEP to produce pyruvate

Different enzymes are used when converting glucose to pyruvate and vice versa and are subject to regulation

Regulation of Glycolysis/Gluconeogensis

• First step is an example of end product inhibtion: glucose-6-phosphate is building up too fast then hexokinase is going to be inhibited

• Last step is an example of feedback inhibition: acetyl-CoA is building up too fast, so then pyruvate kinase is going to be inhibited

• When ATP is high then pyruvate kinase and phosphofructokianse 1 can be inhibted

What is the most important regulatory step?

Fructose-6-phosphate —> fructose-1,6-bisphosphate (phosphofructokinase 1/ F1,6BPase)

(Phosphofructokinase 1 is the most important enzyme)

How does ATP and phosphofructokinase-2 regulate phosphofructokinase 1?

ATP is low, phosphofructokinase 1 step in glycolysis speeds up rapidly

ATP is high, phosphofructokinase 1 step in glycolysis slows down rapidly

Fructose-2,6bisphosphate increases rate of glycolysis and resists ATP’s inhibtory effects

Fructose-2,6bisphosphate

Allosteric activator for phosphofructokinase 1 and increases rate of glycolysis (inhibits glucneogenesis)

Is formed when the second carbon of fructose-6-phosphate is phosphorylated

Most important regulator in glycolysis and gluconeogenesis

Fructose-2,6bisphosphatase

Breaks down fructose-2,6bisphosphate and favors gluconeogenesis