Transcript THE KREBS CYCLE

ECDA
Sept 2009
THE KREBS CYCLE
Krebs Cycle
The Krebs cycle, also known as the
tricarboxylic acid cycle (TCA cycle) or the
citric acid cycle, (or rarely, the SzentGyörgyi-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 acetylCoA 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 4carbon compound, to form citrate, the
starting substrate of TCA cycle.
Krebs Cycle
Krebs Cycle
pyruvate
Acetyl-CoA
CoA
+
NAD+
CO2
+
NADH +
H
Pyruvate dehydrogenase
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.