Glycolysis and the Krebs Cycle

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Glycolysis and the Krebs Cycle

  • Glucose enters cells from the tissue fluid by facilitated diffusion using a specific glucose carrier.
  • This carrier can be controlled (gated) by hormones such as insulin, so that uptake of glucose can be regulated.


  • The first step is the phosphorylation of glucose to form glucose phosphate, using phosphate from ATP.
  • There are two reasons for this step. Firstly, it keeps glucose in the cell by effectively removing “pure” glucose, so glucose will always diffuse down its concentration gradient from the tissue fluid into the cell (glucose phosphate no longer fits the membrane carrier).
  • Secondly, it “activates” glucose for biosynthesis reactions: glucose phosphate is the starting material for the synthesis of pentose sugars(and therefore nucleotides and DNA), glycogen and starch.
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Glycolysis and the Krebs Cycle 2


  • Glucose is phosphorylated again (using another ATP) and split into two triose phosphate(3 carbon) sugars.
  •  From now on everything happens twice per original glucose molecule.


  • The triose sugar is changed over several steps to form pyruvate, a 3-carbon compound.
  •  In these steps some energy is released to form ATP (the only ATP formed in glycolysis), and a hydrogen atom is also released.
  • This hydrogen atom is very important as it stores energy, which is later used by the
    respiratory chain to make more ATP.
  • The hydrogen atom is taken up and carried to the respiratory chain by the coenzyme NAD, which becomes reduced in the process.

(oxidised form of coenzyme →)  NAD + H  →NADH(←reduced form of coenzyme)

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Glycolysis and the Krebs Cycle 3

Pyruvate marks the end of glycolysis, the first stage of respiration. Pyruvate can also be turned back into glucose by reversing glycolysis, and this is called gluconeogenesis.


  • In the absence of oxygen pyruvate is converted into lactate or ethanol in anaerobic respiration.


  • In the presence of oxygen pyruvate enters the mitochondrial matrix to proceed with aerobic respiration.
  • Once pyruvate has entered the inside of the mitochondria (the matrix), it is converted to a compound called acetyl coA.
  • Since this step links glycolysis and the Krebs Cycle, it is referred to as  the link reaction.
  •  In this reaction pyruvate loses a CO2 and a hydrogen to form a 2-carbon acetyl compound, which is temporarily attached to another coenzyme called coenzyme A (or just coA), so the product is called acetyl coA.
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Glycolysis and the Krebs Cycle 4

  • The CO2 diffuses through the mitochondrial and cell membranes by lipid diffusion, out into the tissue fluid and into the blood, where it is carried to the lungs for removal.
  • The hydrogen is taken up by NAD again.


  • The acetyl CoA then enters the Krebs Cycle, named after Sir Hans Krebs.
  • It is one of severa lcyclic metabolic pathways, and is also known as the citric acid cycle or the tricarboxylic acid cycle.
  • The 2-carbon acetyl is transferred from acetyl coA to the 4-carbon oxaloacetate to form the 6-carbon citrate.
  • Citrate is then gradually broken down in several steps to re-form oxaloacetate, producing carbon dioxide and hydrogen in the process.
  • Some ATP is also made directly in the Krebs cycle.
  • As before, the CO2 diffuses out the cell and the hydrogen is taken up by NAD, or by an alternative hydrogen carrier called FAD.
  • These hydrogen atoms are carried to the inner mitochondrial membrane for the final part of respiration.
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