GLUCOSE METABOLISM

AND

CELLULAR RESPIRATION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Submitted to: Prof. R. Logan

Prepared by: Joe Ghorayeb

Course: CHEM 2425

Due date: December 9th 1999

 

 

 

 

This paper, will discuss the event of cellular respiration. It will begin with a brief outline of the four processes involved in cellular respiration, followed by a discussion on the various steps and reactions involved in each process in greater detail and it will conclude with a summary of the events.

The oxidation of glucose is known as cellular respiration. It involves the following processes; glycolysis, the formation of acetyl coenzyme A, the Krebs Cycle, and the Electron Transport Chain. Glycolysis is the oxidation of glucose to pyruvic acid and occurs in most cells in the body. It provides some ATP and energy-containing NADH + H. Because glycolysis does not require oxygen it is known as anaerobic cellular respiration. The formation of acetyl coenzyme A from pyruvic acid is a transition step between glycolysis and the Krebs cycle that prepares pyruvic acid for entrance into the cycle. In this step, energy-containing NADH + H plus carbon dioxide are produced.

Both the Krebs cycle and the electron transport chain require oxygen to produce ATP, they are therefore referred to as aerobic cellular respiration. In the Krebs cycle, acetyl coenzyme A is oxidized and produces ATP, energy containing NADH + H, and FADH as well as carbon dioxide. In the electron transport chain (ETC), NADH + H and FADH are oxidized, therefore contributing their electrons to a series of electron carriers.

The process of glycolysis involves ten chemical reactions that split a six-carbon molecule of glucose into two three-carbon molecules of pyruvic acid. The reactions of glycolysis use two ATP molecules and in turn produce four, a net gain of two ATP molecules. The following represents the ten steps of glycolysis:

 

  1. ATP transfers a phosphate to the six-carbon sugar glucose. The enzyme used to catalyze this reaction is hexokinase.
  2. Glucose 6-phosphate rearranges its structure to form its isomer fructose 6-phosphate. The enzyme used to catalyze this reaction is phosphoglucomutase.
  3. A second ATP transfers a phosphate to create fructose 1,6-bisphosphate. Phosphofructokinase is the enzyme responsible for this reaction, and is the key regulator of the rate of glycolysis.
  4. The fructose ring opens, and the six-carbon fructose 1,6-bisphosphate breaks into two different three-carbon sugar phosphates, Dihydroxyacetone phosphate (DAP) and Glyceraldehyde 3-phosphate (G 3-P). The enzyme responsible for this reaction is aldolase.
  5. Dihydroxyacetone phosphate rearranges to form its isomer glyceraldehyde 3-phosphate. The enzyme responsible for this reaction is isomerase.
  6. The two molecules of G 3-P gain phosphate groups and are oxidized forming two molecules of NADH + H and two molecules of 1,3-bisphosphoglycerate (BPG). The enzyme responsible for this reaction is triose phosphate dehydrogenase.
  7. The two molecules of BPG transfer phosphate groups to ADP forming two ATPs and two molecules of 3-phosphoglycerate (3PG). The enzyme responsible for this reaction is phosphoglycerate kinase.
  8. The phosphate groups on the two 3PGs move, forming two 2-phosphoglycerates (2PG). The enzyme responsible for this reaction is phosphoglyceromutase.
  9. The two molecules of 2PG lose water, becoming two high energy phosphoenolpyruvates (PEP). The enzyme responsible for this reaction is enolase.
  10. Finally, the two PEPs transfer their phosphates to ADP, forming two ATPs and two molecules of pyruvate. The enzyme responsible for this reaction is pyruvate kinase.

Under aerobic conditions, most cells convert pyruvic acid to acetyl coenzyme A. This molecule links glycolysis with the Krebs cycle. However, under anaerobic conditions, pyruvic acid is reduced by the addition of two hydrogen atoms to form lactic acid.

During the transitional step between glycolysis and the Krebs cycle, pyruvic acid is prepared for entrance into the cycle. This is done by the conversion of pyruvic acid to a two-carbon fragment via the removal of a molecule of carbon dioxide. This process is called decarboxylation. During this reaction, NAD is reduced to NADH + H. The two- carbon fragment (acetyl group) then attaches to coenzyme A thus producing the complex acetyl coenzyme A (acetyl CoA). Thus, the acetyl CoA is now ready to enter the Krebs cycle.

The Krebs cycle, also known as the Citric Acid cycle or tricarboxylic acid cycle (TCA), is a series of nine biochemical reactions that occur in the matrix of mitochondria. Below is the series of steps that take place once pyruvic acid is prepared to enter the cycle:

  1. Pyruvate (pyruvic acid) is oxidized to acetate with the formation of NADH + H and the release of carbon dioxide. Acetate is then activated by the combination with coenzyme A, yielding acetyl CoA.
  2. The two-carbon acetyl group and the four-carbon oxaloacetate combine to form a six-carbon citrate.
  3. The citrate then rearranges is structure, forming its isomer isocitrate.
  4. Isocitrate is then oxidized to alpha-ketoglutarate, yielding NADH + H and carbon dioxide.
  5. Alpha-ketoglutarate is then oxidized to succinyl CoA, with the formation of NADH + H and carbon dioxide. The last carbon atoms of glucose are released in this step.
  6. Succinyl CoA releases coenzyme A, thus becoming succinate. The energy released as a result converts GDP to GTP, which in turn converts ADP to ATP.
  7. Here, succinate is oxidized to fumarate, with the formation of FADH.
  8. Fumarate and water react forming malate.
  9. Malate is oxidized to oxaloacetate, with the formation of NADH + H. oxaloacetate can now react with acetyl CoA to reenter the cycle.

Overall, for every two molecules of acetyl CoA that enter the Krebs cycle, 6 NADH, 6 H, and 2 FADH molecules are produced by oxidation-reduction reactions, and two molecules of ATP are generated by substrate level phosphorylation.

In the electron transport chain, the 6 NADH and 6 H will later yield 18 ATP molecules and the 2 FADH will later yield 4 ATP molecules. The reduced coenzymes (NADH and FADH ) are the most important outcome of the Krebs cycle because they contain the energy originally stored in glucose and then in pyruvic acid.

In aerobic cellular respiration, the last electron acceptor of the chain is oxygen. Because this mechanism of ATP generation links chemical reactions with a pumping process, it is called chemiosmosis. Below are the steps involved in the electron transport chain:

  1. The first step is the transfer of high energy electrons from NADH + H to FMN (flavin mononucleotide), the first electron carrier in the the chain. From each molecule of glucose, two NADH + 2 H are generated from glycolysis, two from the formation of acetyl CoA, and six from the Krebs cycle. In this transfer, a hydride ion passes to FMN, which then picks up an additional H from the surrounding aqueous medium. As a result, NADH + H is oxidized to NAD and FMN is reduced to FMNH .
  2. In the second step in the ETC FMNH passes electrons to several iron-sulfur centers and then to Q which picks up an additional H from the surrounding aqueous medium. As a result, FMNH is oxidized to FMN.
  3. The next sequence in the ETC involves cytochromes, iron-sulfur centers, and copper atoms located between Q and molecular oxygen. Electrons are passed successively from Q to cyt b, to Fe-S, to cyt c1, to cyt c, to Cu, to cyt a, and finally to cyt a3. Each carrier in the chain is reduced as it picks up electrons and is oxidized as it gives up electrons. The last cytochrome, cyt a3, passes its electrons to one-half of a molecule of oxygen, which becomes negatively charged and then picks up 2 H from the surrounding medium to form water. This is the only point in aerobic cellular respiration where oxygen is consumed.

The various electron transfers in the ETC generate 32 or 34 ATP molecules from each molecule of glucose that is oxidized. The overall reaction for aerobic respiration is:

C H O + 6 O + 36 or 38 ADPs + 36 or 38 P -------à 6 CO + 6 H O + 36 or 38 ATPs

In conclusion, glycolysis, the Krebs cycle, and especially the electron transport chain provide all the ATP for cellular activities. And because the Krebs cycleand electron chain are aerobic processes, cells cannot carry on their activities for long without sufficient oxygen.

BIBLIOGRAPHY

1.Glycolysis

2.Glycolysis

3.Cellular respiration

4.Krebs Cycle

5.Krebs Cycle

6.

6. Glycolysis,Krebscycleandetc

7.ETC

8.ETC

9. ETC