TCA cycle (Tricarboxylic acid cycle)

The citric acid cycle, also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle—is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate—derived from carbohydrates, fats, and proteins—into carbon dioxide.

1. TCA Cycle
(Tricarboxylicacid cycle)
Anup Muni Bajracharya

2. TCA cycle
•TCA cycle stands for Tricarboxylicacid cycle
•It is also called the Krebs cycle, after Hans Krebs, who first
proposed its cyclic nature.
•Simply it is called as the citric acid cycle which is the central
metabolic hub of the cell.
•The TCA cycle is part of the larger glucose metabolism
whereby glucose is oxidized to form pyruvate, which is then
oxidized and enters the TCA cycle as acetyl-CoA.
•It is the gateway to the aerobic metabolism of any molecule
that can be transformed into an acetyl group or dicarboxylic
acid.

3. Tricarboxylicacid cycle
•More precise defination
•Thecitric acid cycle(CAC)–also
known as theTCA cycle
(tricarboxylicacid cycle)or
theKrebs cycle–is a series
ofchemical reactions used by
allaerobic organismsto release
stored energy through
theoxidationofacetyl-CoAderived
fromcarbohydrates,fats,
andproteins, intoadenosine
triphosphate(ATP) andcarbon
dioxide.

4. Occurence
•The Krebs' cycle reactions take place in the matrix of the
mitochondria.
•This cycle occurs in cytosol in prokaryotes.
•The net result is the production of CO2 when the acetyl group
entering the cycle as Acetyl CoA. In this, the oxidation of
pyruvic acid into carbon dioxide and water occurs.

5. Why TCA is called Amphibolicpathway?
•It is quite obvious that there are both catabolic, and anabolic
pathways thus it is not easy to state which one dominates (it is
not possible to denote the TCA cycle as either catabolic, or
anabolic).
•This is the reason why it is described asamphibolicpathway
Synthesis of important molecules like
succinylCoA (precursor molecule of heme),
oxaloacetate (early intermediate molecule in
gluconeogenesis and substrate for amino acid
synthesis)
Breakdown of carbohydrates

6. Pre TCA cycle
•Glycolysis
At the end of glycolysis, there is two
pyruvate molecules i.ea 6-carbon
glucose molecule is split into two 3-
carbon molecules called pyruvate.
•The transformation of pyruvate to
acetyl CoA
This is a very short step in between
glycolysis and the citric acid cycle.
•The 3-carbon pyruvate molecule made in
glycolysis loses a carbon to produce a
new, 2-carbon molecule called acetyl
CoA.

7. •The steps above are carried out by a large enzyme complex
called thepyruvate dehydrogenase complex, which consists
of three interconnected enzymes and includes over 60
subunits.

8. Elaborated form

9. Combined form

10. The citric acid cycle
•The citric acid cycle is called a cycle because the starting
molecule, oxaloacetate (which has 4 carbons), is regenerated
at the end of the cycle.
•Throughout the citric acid cycle, oxaloacetate is progressively
transformed into several different molecules (as carbon atoms
are added to and removed from it), but at the end of the cycle
it always turns back into oxaloacetate to be used again.
•The released energy is captured as the electron shuttles
(NADand FAD) are reduced to NADH and FADH

11. Reaction 1: Synthesis of Citric
Acid
•The first reaction of the cycle is the condensation ofthe two-
carbon compound acetyl-CoAwiththe four-carbon compound
oxaloacetateto formcitrate.
•The Citrate is a tricarboxylicacid, and the Krebs cycle is also
known as the tricarboxylicacid (or TCA) cycle
•This reaction is catalyzed by citrate synthase.

12. Reaction 2: Isomerization of
Citrate
•Thecitrateis rearranged to form an isomeric form,isocitrateby
an enzymeacontinase.
•This process involves a sequential dehydration and hydration
reaction, to form the Isocitrateisomer with cis-Aconitaseas the
intermediate.
•A single enzyme, Aconitase, performs this two-step process.

13. Reaction 3: Oxidation of Isocitrateto
α-Ketoglutarate
•It’s a two-step reaction in which there is first an oxidation, and
then a decarboxylation. CO
2is produced, and the electrons are
passed to NAD+ to form NADH and H+.
•The enzymeisocitratedehydrogenasecatalyzes the oxidation
of the –OH group at the 4′ position of isocitrateto yield an
intermediate oxalosuccinatewhich then has a carbon dioxide
molecule removed from it to yieldalpha-ketoglutarate.

14. Reaction 4: Oxidation of α-Ketoglutarate
to Succinyl-CoA
•Alpha-ketoglutarateis oxidized, carbon dioxide is removed,
and coenzyme A is added to form the 4-carbon
compoundsuccinyl-CoA.
•During this oxidation, NAD+ is reduced to NADH + H+.The
enzyme that catalyzes this reaction isalpha-ketoglutarate
dehydrogenase.

15. Reaction 5: Conversion of Succinyl-CoA
to Succinate
•CoA is removed fromsuccinyl-CoAto producesuccinate.
•The energy released is used to make guanosinetriphosphate
(GTP) from guanosinediphosphate(GDP) and Pi by substrate-
level phosphorylation. GTP can then be used to make ATP.
•The enzymesuccinyl-CoA synthasecatalyzes this reaction of
the citric acid cycle.

16. Reaction 6: Oxidation of Succinate to
Fumarate
•Succinateis oxidized tofumarate.
•The hydrogen acceptor is the coenzyme FAD instead of the
more usual NAD+.
•During this oxidation, FAD is reduced to FADH2.The
enzymesuccinate dehydrogenasecatalyzes the removal of
two hydrogensfrom succinate.
•

17. Reaction 7: Hydration of Fumarateto
Malate
•The reversible hydration offumarateto malateis catalyzed
byfumarase(fumaratehydratase).
•Fumarasecontinues the rearrangement process by
addingHydrogenandOxygenback into the substrate that had
been previously removed i.ewater is added to the four-carbon
molecule fumarate, converting it into another four-carbon
molecule called malate.

18. Reaction 8: Oxidation of Malate to
Oxaloacetate
•Malateis oxidized to produceoxaloacetate, the starting
compound of the citric acid cyclebymalate dehydrogenase.
•During this oxidation, the coenzyme NAD+ causes the transfer
of two hydrogensand 2 electrons to NADH + H
+
.

20. Significance ofKrebs Cycle
•Formation of NADH and FADH
2for entrance into the electron
transport chain and subsequent ATP generation.
•Krebs cycle (citric Acid cycle) releases plenty of energy (ATP)
required for various metabolic activities of cell.
•Intermediate compounds formed during Krebs cycle are used
for the synthesis of biomolecules like amino acids,
nucleotides, chlorophyll, cytochromes and fats etc.
•Intermediate like succinylCoA takes part in the formation of
chlorophyll.
•Amino Acids are formed from α-Ketoglutaricacid, pyruvic
acids and oxaloaceticacid.