Why is it beneficial to convert pyruvate to lactate when oxygen is not available?

Glucose is the monosaccharide utilized by most eukaryotes to generate metabolic energy, and in the majority of eukaryotic systems, glycolysis is the first biochemical pathway where glucose breaks down via a series of enzymatic reactions to produce relatively small amounts of adenosinetriphosphate (ATP). In 1940, the sequence of these glycolytic reactions was elucidated, a breakthrough that was recognized as the very first such elucidation of a biochemical pathway in history. Accordingly, the glycolytic breakdown of glucose ends up either with pyruvate as the final product under aerobic conditions or with lactate, to which pyruvate is being reduced, under anaerobic conditions. Consequently, pyruvate has been designated and is held to be the substrate of the mitochondrial tricarboxylic acid cycle, where it is completely oxidized into CO2 and H2O, while lactate has been defined and being held to as a useless dead-end product, poisonous at times, of which cells must discard off quickly. More than four decades after the glycolytic pathway has been elucidated, studies of both muscle and brain tissues have suggested that lactate is not necessarily a useless end product of anaerobic glycolysis and may actually play a role in bioenergetics. These studies have shown that muscle and brain tissues can oxidize and utilize lactate as a mitochondrial energy substrate. These results have been met with great skepticism, but a large number of publications over the past quarter of a century have strengthened the idea that lactate does play an important and, possibly, a crucial role in energy metabolism. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway, that is, its inability to regenerate nicotinamide adenine dinucleotide (oxidized form) (NAD+), as opposed to anaerobic glycolysis that features the cyclical ability of the glycolytic lactate dehydrogenase (LDH) system to regenerate NAD+ upon pyruvate reduction to lactate. An examination of scientific investigations on carbohydrate metabolism of brain tissue in the 1920s and 1930s has already revealed that lactate can be readily oxidized. However, due to the prevailing dogma, according to which lactate is a waste product, its oxidation was assumed to be a possible mechanism of elimination. This chapter examines both old and new research data on glucose glycolysis both in muscle and in brain tissues. This chapter consolidates the available data in an attempt to form a more accurate and clear description of this universal and very important bioenergetic chain of reactions.

• Lipids are not preferentially used as they are harder to transport and digest (although will yield more energy per gram)
• Proteins are not preferentially used as they release potentially toxic nitrogenous compounds when broken down

The first step in the controlled breakdown of carbohydrates is glycolysis, which occurs in the cytosol of the cell

• In glycolysis, a hexose sugar (6C) is broken down into two molecules of pyruvate (3C)

The process of glycolysis involves many intermediate steps, but can be summarised by four key events:

1.  Phosphorylation

• A hexose sugar (typically glucose) is phosphorylated by two molecules of ATP (to form a hexose bisphosphate)
• This phosphorylation makes the molecule less stable and more reactive, and also prevents diffusion out of the cell 

2.  Lysis

• The hexose biphosphate (6C sugar) is split into two triose phosphates (3C sugars)

3.  Oxidation

• Hydrogen atoms are removed from each of the 3C sugars (via oxidation) to reduce NAD+ to NADH (+ H+)
• Two molecules of NADH are produced in total (one from each 3C sugar)

4.  ATP formation

• Some of the energy released from the sugar intermediates is used to directly synthesise ATP
• This direct synthesis of ATP is called substrate level phosphorylation
• In total, 4 molecules of ATP are generated during glycolysis by substrate level phosphorylation (2 ATP per 3C sugar)

At the end of glycolysis, the following reactions have occurred:

• Glucose (6C) has been broken down into two molecules of pyruvate (3C)
• Two hydrogen carriers have been reduced via oxidation (2 × NADH + H+)
• A net total of two ATP molecules have been produced (4 molecules were generated, but 2 were used)

Overview of Glycolysis

Understanding:

•  Glycolysis gives a small net gain of ATP without the use of oxygen

    
Glycolysis involves the breakdown of glucose into pyruvate (× 2), with a small net gain of ATP (two molecules)

• Glycolysis occurs in the cytosol and does not require oxygen (it is an anaerobic process)

Depending on the availability of oxygen, the pyruvate may be subjected to one of two alternative processes:

• Aerobic respiration occurs in the presence of oxygen and results in the further production of ATP (~ 34 molecules)
• Anaerobic respiration (fermentation) occurs in the absence of oxygen and no further ATP is produced

Aerobic Respiration

• If oxygen is present, the pyruvate is transported to the mitochondria for further breakdown (complete oxidation)
• This further oxidation generates large numbers of reduced hydrogen carriers (NADH + H+ and FADH2)
• In the presence of oxygen, the reduced hydrogen carriers can release their stored energy to synthesise more ATP
• Aerobic respiration involves three additional processes – the link reaction, krebs cycle and the electron transport chain

Anaerobic Respiration (Fermentation)

• If oxygen is not present, pyruvate is not broken down further and no more ATP is produced (incomplete oxidation)
• The pyruvate remains in the cytosol and is converted into lactic acid (animals) or ethanol and CO2 (plants and yeast)
• This conversion is reversible and is necessary to ensure that glycolysis can continue to produce small quantities of ATP
  • Glycolysis involves oxidation reactions that cause hydrogen carriers (NAD+) to be reduced (becomes NADH + H+)
  • Typically, the reduced hydrogen carriers are oxidised via aerobic respiration to restore available stocks of NAD+
  • In the absence of oxygen, glycolysis will quickly deplete available stocks of NAD+, preventing further glycolysis
  • Fermentation of pyruvate involves a reduction reaction that oxidises NADH (releasing NAD+ to restore available stocks)
  • Hence, anaerobic respiration allows small amounts of ATP to be produced (via glycolysis) in the absence of oxygen

    Why is pyruvate converted to lactate in the absence of oxygen?

    If a cell lacks mitochondria, is poorly oxygenated, or energy demand has rapidly increased to exceed the rate at which oxidative phosphorylation can provide sufficient ATP, pyruvate can be converted to lactate by the enzyme lactate dehydrogenase.

    What is the purpose of converting pyruvate to lactate?

    In the absence of oxygen (anaerobic), pyruvate must be converted to lactic acid, the only reaction that can regenerate NAD⁺ allowing further glycolysis.

    What happens to pyruvate if oxygen is not available?

    When oxygen is not present or if an organism is not able to undergo aerobic respiration, pyruvate will undergo a process called fermentation. Fermentation does not require oxygen and is therefore anaerobic. Fermentation will replenish NAD+ from the NADH + H+ produced in glycolysis.

    Why is it beneficial for pyruvate to be reduced via fermentation when oxygen is not available?

    Why is it beneficial for pyruvate to be reduced via fermentation when oxygen is not available? All of the choices are advantages: -The organism can survive short spells of anaerobic conditions and maintain growth and reproduction. -Fermentation can provide a rapid burst of ATP.