NAD+ Regeneration – The Catabolism of Pyruvate

Question 1

Maintaining Redox Balance

Answer 1

• In a cell, only limited amounts of NAD+ are present
• NAD+ is derived from the vitamin, niacin
• Glycolysis reduces NAD+ to NADH + H+
• For glycolysis to continue, NADH must be re-oxidised
• NAD+ is regenerated through the metabolism of pyruvate
• Even though pyruvate is important, it cannot be an end-product

Question 2

When do glycolysis and cellular respiration occur?

Answer 2

in aerobic conditions i.e. with oxygen present

Question 3

When do glycolysis and fermentation occur?

Answer 3

in anaerobic conditions i.e. without oxygen present

Question 4

The fate of pyruvate in anaerobic reactions

Answer 4

• alcohol fermentation: pyruvate and ethanol are formed from yeast and some microorganisms in the absence of oxygen
• first converted into acetaldehyde, which gives off ethanol
• alcohol dehydrogenase is the enzyme
• lactic acid fermentation: pyruvate is converted to lactate via some microorganisms and humans in the absence of oxygen
• The NADH generated during glycolysis donate their electrons to pyruvate itself and that pyruvate becomes lactate
• lactate dehydrogenase is the enzyme.

Question 5

The fate of pyruvate in aerobic reactions

Answer 5

• when pyruvate is further oxidised in the presence of oxygen, much more energy is released
• occurs in all aerobic organisms
• Much more efficient
• These NADHs can now donate their electron
• Pyruvate can now be oxidised
• CO2 and more NADH is oxidised
• The arrow pointing down at citric acid cycle is misleading
• All Cs released in glycolysis released as CO2

Question 6

Lactic acid fermentation

Answer 6

• This occurs in many microorganisms such as cheese
• Another example is muscle during anaerobic exercise (soreness because of low pH; eliminated in liver, heart and resting working muscle)
• Training (stops lactate production; increases the clearance of lactate)
• Endurance performance is predicted by plasma lactate during exercise
• This lactic acid can be converted back to pyruvate in the liver, heart and resting and working muscle, but not immediately

Question 7

Alcohol Fermentation

Answer 7

• Occurs in some plants and yeasts e.g. bread, alcohol
• First evidence 7000BC
• pyruvate and ethanol are formed from yeast and some microorganisms in the absence of oxygen
• first converted into acetaldehyde, which gives off ethanol
• alcohol dehydrogenase is the enzyme
• continues when pyruvate needs to help NADH become re-oxidised
• two pyruvates lose a CO2 each
• Alcohol dehydrogenase reaction
• Donate hydrogen from NADH to acetaldehyde

Question 8

Mitochondria

Answer 8

• Contains proteins for electron transport chain, ATP synthase and transport proteins
• Contains enzymes of the TCA cycle

Question 9

Aerobic Metabolism of Pyruvate

Answer 9

• A specific transporter allows pyruvate to enter mitochondria
• The pyruvate dehydrogenase complex (PDC) catalyses the oxidative decarboxylation of pyruvate to acetyle-CoA

Question 10

Pyruvate Dehydrogenase Complex

Answer 10

• PDC consists of 3 enzymes involved in the actual reaction mechanism: E1, E2 and E3
• As well as 2 enzymes involved in the control of PDC – a kinase and a phosphatase in a single polypeptide
• And 5 coenzymes: thiamine, lipoic acid, coenzyme A, FAD and NAD+
• The activity of the PDC is the major determinant of glucose oxidation in well oxygenated tissues in vivo
• THIS IS AN IRREVERISBLE REACTION
• Acetyl-CoA cannot be converted into pyruvate!

Question 11

Electron carriers

Answer 11

• NAD must be recycled
• Important electron carrier
• One of the reasons we have an intermediate is because it allows us to separate between the arrows on the diagram
• Oxidation of A cannot occur if NAD+ is not available
• Oxidation of B cannot occur if NADH is not available

Question 12

Further oxidation of pyruvate

Answer 12

• What happens next is dependent on the presence/absence of oxygen
• Glycolysis and cellular respiration occur in aerobic conditions i.e. with oxygen present
• Terminal electron acceptor = oxygen
• Glycolysis and fermentation occur in anaerobic conditions i.e. without oxygen present
• Pyruvate or something related will have to accept electrons from NADH and FADH2 and so will not be able to progress to citric acid cycle