(TRICARBOXYLIC ACID

(TCA)CYCLE/CITRIC ACID CYCLE)

Activity: encsarmeblU eM!
Breks Celyc

Krebs Cycle
●

●The cycle produces carbon dioxide and the energy-rich

compound ATP.
Lacety Aoc

Acetyl CoA
●

●A molecule that participates in many biochemical reactions

in protein, carbohydrate and lipid metabolism
Oclimetab Swapyhat

Metabolic Pathways
●

Series of chemical reactions in a cell that build and

●

breakdown molecules for cellular processes

Adrionchotim

Mitochondria
●

The citric acid cycle enzymes are found in the matrix of the
●

mitochondria
Croban exidiod

Carbon dioxide
●

A by-product of Krebs Cycle

●
Let us study.
METABOLIC PATHWAYS
A series of consecutive biochemical reactions catalyzed by
●

enzymes that produce a specific end product.

●Catabolism- the breakdown of food stuffs to simple organic
chemicals.
Anabolism- the synthesis of biomolecules from simple
●

organic chemicals.
METABOLIC PATHWAYS
Very Few metabolites are used to synthesize a large
●

variety of biomolecules:
Acetyl-Coenzyme A (acetyl-CoA)
●

Pyruvate
●

Citrate acid cycle intermediates

●
METABOLIC PATHWAYS
Three main pathways for energy production:
●

Glycolysis- the metabolic pathway that converts glucose

●

C6H12O6, into pyruvate

Citric acid cycle (or the Krebs Cycle)
●

●Oxidative-Phosphorylation- the process in cell metabolism by

which respiratory enzymes in the mitochondria synthesize ATP
from ADP and inorganic phosphate during the oxidation of
NADH by molecular oxygen.
METABOLIC PATHWAYS

●Certain pathways are

involved in both
breakdown and
buildup of molecules
these pathways are
called amphibolic.
The citric acid cycle is
an example of this.
OVERALL GOAL/IMPORTANCE
Makes ATP
●

Makes NADH
●

Makes FADH2
●

●
A cyclical series of biochemical reactions that is fundamental to the metabolism of aerobic
organisms, i.e. animals, plants, and many microorganisms
Geography

●Krebs in mitochondrial matrix

●Mitochondrion

–Outer membrane very permeable

•Space between membranes called intermembrane space
–Inner membrane (cristae)
•Permeable to pyruvate,
•Impermeable to fatty acids, NAD, etc
–Matrix is inside inner membrane
The citric acid cycle enzymes are found
in the matrix of the mitochondria
OVERVIEW
Described by Hans Adolf Krebs in 1937
●

A feature of cell chemistry shared by all types of life.

●

●A complex series of reactions beginning and ending with the

compound oxaloacetate.
●The cycle produces carbon dioxide and the energy-rich
compound ATP.
OVERVIEW
Eight successive reaction steps.
●

The six carbon citrate is formed from two carbon acetyl-CoA

●

and four carbon oxaloacetate.

Oxidation of citrate yields CO2 and regenerates oxaloacetate.
●

The energy released is captured in the reduced coenzymes

●

NADH and FADH2.

Conversion of pyruvate to
Acetyl CoA
NAD+ NADH HSCoA CO2 O
O
O SCoA
H3C H3C
O
p yruv ate d e h y dro g e n a s e c o m plex a c etyl C o A

pyruv ate

●2 per glucose (all of Kreb’s)

●Oxidative decarboxylation

●Makes NADH
Fates of Acetyl CoA
O
K re b's
T A G 's H3C SCoA
a c etyl C o A C O 2, A T P , N A D H ... e n e r g y

n o C H O prese nt

k eto n e b o dies

In the presence of CHO

●

–Metabolized to CO2, NADH, FADH2,GTP and, ultimately, ATP

If energy not being used (Lots of ATP present)
●

–Made into fat

If energy being used, but no CHO present
●

–Starvation
–Forms ketone bodies (see fat metabolism slides)
–Danger!
Kreb’s Cycle
acetyl CoA
H3C SCoA
C
O O
O
CoASH C
O O O H 2O
O + CH2 O
C NADH C
NAD
C O
HO C C O
HC OH citrate synthase CH2
CH2
H2O CH2 malate C citrate
dehydrogenase
C O O
O O C O
O
fumarase O
C O oxaloacetate
C H malate
aconitase
H C fumarate

O
C
O Kreb's Cycle O O
FADH2 C
succinate
dehydrogenase HO CH O
HC C O
FAD alpha ketoglutarate CH2
O SCoA O C isocitrate
O GTP
NADH O O
C NAD C
CoASH C NADH O O
CH2 CH2 C O CO2 NAD
CH2 GDP CH2
CH2 CoASH
C C CO2 CH2
succinyl CoA isocitrate dehydrogenase
O O synthetase O O alpha ketoglutarate C
succinate succinyl CoA
dehydrogenase
O
O
1. Citrate Synthase Reaction
O O O
C O
C
C O H2O CoASH
C H2 O
H3C SCoA C H2
C C HO C C O
O + O
O
c it r a t e s y n t h a s e C H2
C
O O
a c etyl C o A o x alo a c etate
c it r a t e
2. Aconitase Reaction

O O O O
C C
C H2 O
HO CH O
HO C C O HC C O
C H2 C H2
a c o n it a s e
C C
O O
O O

c it r a t e i s o c it r a t e

● Forms isocitrate
3. Isocitrate Dehydrogenase

O O
O O C
C C O
HO CH O
NAD NADH CO2 CH 2
HC C O CH 2
CH 2
C C
O O isocitrate dehydrogenase O O

isocitrate alpha ketoglutarate

● All dehydrogenase reactions make NADH or FADH2

4. α-ketoglutarate dehydrogenase
O O
C SCoA O
C O
C
C H2 C O2 NADH
CoASH NAD C H2
C H2
C H2
C C
O O O O
alp h a k eto glutarate
d e hydro g e n as e
alp h a k eto glutar ate s u c c i n yl C o A

Same as pyruvate dehydrogenase reaction

●
5. Succinyl CoA synthetase
SCoA O O
O
C C
CH2 GTP CoASH CH2
GDP
CH2 CH2
C C
O O succinyl CoA O O
succinyl CoA synthetase
succinate

Coupled to synthesis of GTP

●

–GTP very similar to ATP and interconverted later

6. Succinate dehydrogenase
O O O
O
C FA D H C
C H FA D 2
C H
2
C H 2 H C
C s u c cin yl C o A
C
O O
O O dehydrogenase

s u c cin ate fu m arate

●Dehydrogenation
●Uses FAD
7. Fumarase
O O O O
C H2O C
C H HC OH
H C C H2
C fu m arase
C
O O O
O
fu m arate
m alate

Addition of water to a double bond

●
8. Malate Dehydrogenase
O O
C O O
HC OH C
NAD NADH C O
CH2 CH2
C C
O O malate O
dehydrogenase O
malate
oxaloacetate

●Makes NADH
●Regenerates oxaloacetate for another round
Net From Kreb’s
Oxidative process
●

–3 NADH
–FADH2
–GTP
X 2 per glucose
●

–6 NADH
–2 FADH2
–2 GTP
All ultimately turned into ATP (oxidative
●

phosphorylation)
Take a short test!
Direction: Write the term that corresponds to the statements.

1. Cellular organelle that produces energy for the cell. ______________

2. How many succesive steps involves in a Kreb Cycle? ____________

3. The metabolic pathway that converts glucose C6H12O6, into pyruvate _________

4. The energy currency of life. ____________

5. A biochemical pathway that involves both catabolism and anabolism. __________

Check your answers.

1. mitochondria 4. ATP
2. 8 5.
amphibolic
Thank you.

RODEL M. CATAJAY
TIII-SHS