ECDASept 2009

Krebs Cycle

The Krebs cycle, also known as the tricarboxylic acid cycle (TCA cycle) or the citric acid cycle, (or rarely, the Szent-Györgyi-Krebs cycle) is a series of enzyme-catalysed chemical reactions of central importance in all living cells that use oxygen as part of cellular respiration.

Krebs Cycle In aerobic processes, the citric acid cycle is

part of a metabolic pathway involved in the chemical conversion of carbohydrates, lipids, and proteins into carbon dioxide and water to generate a form of usable energy.

The cycle occurs in the matrix of the mitochondrion of eukaryotic cells.

The citric acid cycle is the third step in CHO metabolism (the breakdown of sugars).

The process is continuously supplied with new carbons in the form of acetyl-CoA

Krebs Cycle

Acetyl-CoA, a 2-carbon compound linked to a coenzyme, is continuously produced from pyruvate molecule via oxidative decarboxylation process

The pyruvate molecules used to produce acetyl-CoA are mostly coming from the pyruvate molecules made from the glycolysis pathway.

Krebs Cycle

REVIEW THE EMBDEN-MEYERHOF PATHWAY! For every glucose molecule entering

glycolysis, 2 molecules of pyruvates are formed as the end product.

The pyruvate molecules can become lactic acid via process of fermentation when oxygen is absent (anaerobic respiration)

Pyruvate can be metabolized to become acetyl-CoA and later enter the TCA cycle as part of aerobic respiration.

Krebs Cycle

The conversion of pyruvate to acetyl-CoA is not technically a part of glycolysis.

The reaction is carried out in the mitochondria, unlike the reactions of glycolysis which happen in the cytosol.

It commits pyruvate to entering the citric acid cycle by reacting with oxaloacetate, a 4-carbon compound, to form citrate, the starting substrate of TCA cycle.

Krebs Cycle

Krebs Cycle

pyruvate Acetyl-CoA

Pyruvate dehydrogenase

CoA+

NAD+

CO2+

NADH + H

Krebs Cycle

Krebs Cycle The citric acid cycle begins with acetyl-

CoaA transferring its two-carbon acetyl group to the four-carbon acceptor compound (oxaloacetate) to form a six-carbon compound (citrate). The enzyme is citrate synthase.

The citrate then goes through a series of chemical transformations becoming isocitate, losing its first carboxyl group as CO2 .

Starting with isocitrate, a second carboxyl group as CO2 is released and one NADH molecule is produced before another intermediate substrate, α-ketoglutarate, is formed.

Krebs Cycle

Krebs Cycle The second carbon as CO2 is released from

α-ketoglutarate during its transformation to succinate. Another NADH molecule is produced and one ATP molecule is made in this reaction.

Succinate is then transformed into fumarate in the next step of the cycle. In this reaction, the enzyme succinate dehydrogenase acts on the metabolism of succinate and forms one FADH2 molecule in the process.

This FADH2 molecule enters the ETC through Complex II. (Remember ETC!)

Krebs Cycle

Krebs Cycle

Fumarate becomes malate through the addition of water into the former.

Malate then is oxidized to form oxaloacetate, the 4-carbon compound that binds with acetyl-CoA to produce citrate.

During oxaloacetate formation from malate, the 3rd and last NADH compound is also formed.

This last step ensures the continuous formation of citrate, hence continuous TCA cycle.

Krebs Cycle

Krebs Cycle

REVIEW: STARTING SUBSTRATES: acetyl-

CoA and oxaloacetate END PRODUCT SUBSTRATE:

oxaloacetate NADH formed per cycle: 3 FADH2 formed per cycle: 1 ATP/GTP formed per cycle: 1

Krebs Cycle

Since 2 acetyl-CoAs are formed for every one glucose molecule, 2 cycles of Krebs cycle are required to completely metabolize one glucose.

So the over-all products of TCA cycle are: 6 NADH 2 FADH2 2 ATP/GTP 4 CO2

QUESTION Therefore:

HOW MANY ATP MOLECULES CAN BE PRODUCED FROM ONE GLUCOSE MOLECULE AFTER ITS COMPLETE METABOLISM?

HINT: Glycolysis, TCA cycle, ETC

ANSWER:

An estimate for the total number of ATP obtained after complete oxidation of one glucose in glycolysis, citric acid cycle, and oxidative phosphorylation given in

the literature is 38 molecules of ATP.