METABOLISM

DEFINISI
• Metabolism is the biochemical modification of
chemical compounds in living organisms and
cells.
• This includes the biosynthesis of complex
organic molecules (anabolism) and their
breakdown (catabolism).
• Metabolism usually consists of sequences of
enzymatic steps, also called metabolic
pathways.
• The total metabolism are all biochemical
processes of an organism.
• The cell metabolism includes all chemical
processes in a cell. Without metabolism we
would not be able to survive.
 Catabolism
Catabolic pathways that breakdown complex molecules into simple compounds:
• Cellular respiration, metabolic pathways that create energy (ATP and
NADPH) from fuel molecules. These pathways are also involved in the digestion
of food.
– Carbohydrate catabolism
• Glycogenolysis, the conversion of glycogen into glucose.
• Glycolysis, the conversion of glucose into pyruvate and ATP, does not
require oxygen.
– Embden-Meyerhof pathway, the common glycolysis pathway.
– Entner-Doudoroff Pathway, an alternative glycolysis pathway in few
bacteria.
• Pentose phosphate pathway (hexose monophosphate shunt), generation
of NADPH from glucose.
– Protein catabolism, the hydrolysis of proteins into amino acids.
• Aerobic respiration
– Electron transfer chain
– Oxidative phosphorylation
• Anaerobic respiration,
– Lactic acid fermentation
– Fermentation
 Anabolism
Anabolic pathways that create building blocks and
compounds from simple precursors:
• Glycogenesis
• Gluconeogenesis
• Porphyrin synthesis pathway
• HMG-CoA reductase pathway, leading to cholesterol and
isoprenoids.
• Secondary metabolism, metabolic pathways that are not
essential for growth, development or reproduction, but
that usually have ecological function.
• Photosynthesis
– Light-dependent reaction (light reaction)
– Light-independent reaction (dark reaction)
• Carbon fixation
Glycolysis, the Universal Process

• Nine reactions, each catalyzed by a specific

enzyme, makeup the process we call
glycolysis. ALL organisms have glycolysis
occurring in their cytoplasm.
• At steps 1 and 3 ATP is converted into ADP,
inputting energy into the reaction as well as
attaching a phosphate to the glucose. At
steps 6 and 9 ADP is converted into the
higher energy ATP. At step 5 NAD+ is
converted into NADH + H+.
• The process works on glucose, a 6-C, until
step 4 splits the 6-C into two 3-C compounds.
Glyceraldehyde phosphate (GAP, also known
as phosphoglyceraldehyde, PGAL) is the
more readily used of the two.
Dihydroxyacetone phosphate can be
converted into GAP by the enzyme
Isomerase. The end of the glycolysis process
yields two pyruvic acid (3-C) molecules, and
a net gain of 2 ATP and two NADH per
glucose.
• Graphic summary of the glycolysis process.
Image from Purves et al., Life: The Science of
Biology, 4th Edition, by Sinauer Associates
(www.sinauer.com)
 Anaerobic Pathways
• Under anaerobic conditions, the absence
of oxygen, pyruvic acid can be routed by
the organism into one of three pathways:
lactic acid fermentation, alcohol
fermentation, or cellular (anaerobic)
respiration. Humans cannot ferment
alcohol in their own bodies, we lack the
genetic information to do so.
Alcohol fermentation is the formation of alcohol from
sugar. Yeast, when under anaerobic conditions,
convert glucose to pyruvic acid via the glycolysis
pathways, then go one step farther, converting
pyruvic acid into ethanol, a C-2 compound.
• Many organisms will also ferment pyruvic acid
into, other chemicals, such as lactic acid.
Humans ferment lactic acid in muscles where
oxygen becomes depleted, resulting in localized
anaerobic conditions.
 Aerobic Respiration

• When oxygen is present (aerobic

conditions), most organisms will
undergo two more steps, Kreb's Cycle,
and Electron Transport, to produce their
ATP. In eukaryotes, these processes
occur in the mitochondria, while in
prokaryotes they occur in the
cytoplasm.
Overview of the cellular respiration processes. Image from
Purves et al., Life: The Science of Biology, 4th Edition, by
Sinauer Associates (www.sinauer.com)
1.Condensation
2.a. Dehydration
2.b. Hydration
3. Oxidative decarboxilation
4. Oxidative decarboxilation
5. Substrat level
Phosphorilation
6. Dehydrogenation
7. Hydration
8. Dehydrogenation
 Step 1: Condensation
• In step 1 of the Krebs cycle, the two-
carbon compound, acetyl-S-CoA,
participates in a condensation reaction
with the four-carbon compound,
oxaloacetate, to produce citrate:
 Step 2. Isomerization of Citrate
• The citric acid molecule undergoes an isomerization. A
hydroxyl group and a hydrogen molecule are removed from the
citrate structure in the form of water. The two carbons form a
double bond until the water molecule is added back. Only now,
the hydroxyl group and hydrogen molecule are reversed with
respect to the original structure of the citrate molecule. Thus,
isocitrate is formed.
 Step 3: Generation of CO2 by an NAD+
linked enzyme
• In this step, the isocitrate molecule is oxidized by a NAD
molecule. The NAD molecule is reduced by the
hydrogen atom and the hydroxyl group. The NAD binds
with a hydrogen atom and carries off the other hydrogen
atom leaving a carbonyl group. This structure is very
unstable, so a molecule of CO2 is released creating
alpha-ketoglutarate.
 Step 4: A Second Oxidative
Decarboxylation Step
• In this step, coenzyme A, returns to oxidize the alpha-
ketoglutarate molecule. A molecule of NAD is reduced
again to form NADH and leaves with another
hydrogen. This instability causes a carbonyl group to be
released as carbon dioxide and a thioester bond is
formed in its place between the former alpha-
ketoglutarate and coenzyme A to create a molecule of
succinyl-coenzyme A complex.
Step 5: Substrate-Level Phosphorylation

• A water molecule sheds its hydrogen atoms to

coenzyme A. Then, a free-floating phosphate
group displaces coenzyme A and forms a bond
with the succinyl complex. The phosphate is
then transferred to a molecule of GDP to
produce an energy molecule of GTP. It leaves
behind a molecule of succinate.
 Step 6: Flavin-Dependent
Dehydrogenation

• In this step, succinate is oxidized by a molecule

of FAD (Flavin adenine dinucleotide). The FAD
removes two hydrogen atoms from the succinate
and forces a double bond to form between the
two carbon atoms, thus creating fumarate.
 Step 7: Hydration of a Carbon-Carbon
Double Bond
• An enzyme adds water to the fumarate molecule
to form malate. The malate is created by
adding one hydrogen atom to a carbon atom
and then adding a hydroxyl group to a carbon
next to a terminal carbonyl group.
Step 8: A Dehydrogenation Reaction that
will Regenerate Oxaloacetate
• In this final step, the malate molecule is oxidized
by a NAD molecule. The carbon that carried the
hydroxyl group is now converted into a carbonyl
group. The end product is oxaloacetate which
can then combine with acetyl-coenzyme A and
begin the Krebs cycle all over again.
 Summary
• In summary, three major events occur during the
Krebs cycle. One GTP (guanosine
triphosphate) is produced which eventually
donates a phosphate group to ADP to form one
ATP; three molecules of NAD are reduced; and
one molecule of FAD is reduced. Although one
molecule of GTP leads to the production of one
ATP, the production of the reduced NAD and
FAD are far more significant in the cell's energy-
generating process. This is because NADH and
FADH2 donate their electrons to an electron
transport system that generates large amounts
of energy by forming many molecules of ATP.
 Electron Transport Chain and Oxidative
Phosphorylation

• Most of the ATP created from the energy stored in the glucose
is produced by oxidative phosphorylation when NADH and
FADH2 donate their electrons to a system of electron carriers
embedded in the mitochondrial cristae.
• The electron transport chain consists of a series of increasingly
electronegative components, starting with a flavoprotein
progressing through an iron-sulfur protein, then to ubiquinone
and a series cytochrome proteins with iron containing heme
groups, and finally reaching oxygen which is very
electronegative.
• The components of the chain receive electrons from NADH and
FADH2 and shifts between reduced and oxidized states,
passing electrons down an energy gradient to oxygen, which
then picks up a pair of hydrogen ions and forms water. Two
mobile components, Q and cytochrome c, transfer electrons
between the other electron carriers, which are located in three
groups of integrated complexes.
• The structural order of the carriers causes electron
transfers at three steps along the chain to translocate H+
from the matrix to the intermembrane space, storing
energy in an electrochemical gradient known as the
proton-motive force. As hydrogen ions diffuse back the
matrix through ATP synthase complexes on the christae,
the exergonic passage of H+ drives the endegonic
phosphorylation of ADP.
• The complete oxidation of glucose to carbon dioxide
during aerobic respiration in eukaryotes produces a net
yield of about 36 molecules of ATP, compared to only 2 for
incomplete oxidation.
• The actual yield of ATP during respiration varies, owing to
differences in the permeability of the christae to H+ and to
partial use of the proton gradient to drive the active
transport of certain solutes across the outer mitocondrial
membrane.
Cytochrome system: hydrogen carrier system;
electron transfer system
 Aerobi Anaerobic
c
2 ATP used in glycolysis ==================> -2 ATP -2 AT P

4 ATP formed in glycolysis ================> +4 ATP +4 ATP

2 NADH2 formed in glycolysis ====via e.t.==> +6 ATP

8 NADH2 formed in Kreb's cycle ===via e.t.==> +24

ATP

2 GTP in Kreb's cycle =====================> +2 ATP

2 FADH2 in Kreb's cycle ===via e.t.=========> +4 ATP

Total: 38 ATP 2 ATP

 GLUKONEOGENESIS
• D-Glukosa esensial utk fungsi normal
kebanyakan sel
• D-Glu merup kebut absolut utk sistem syaraf
dan eritrosit
• If, diet kurang D-Glu  kadar glukosa darah
me,  tubuh menanggapi dgn mensintesis D-
Glu dr senyawa prekursor bukan KH
• Glukoneogenesis = proses p’btk kembali
glukosa dr prekursor bukan KH sbg respon
rendahnya kadar gula darah. Berlangsung dlm
hati dan ginjal
• Sumber C utk glukoneogensis  senywa
prekursor glukogenik t’utama b’asal dr as.
Amino L, spt : L-prolin, L-arginin, dll
• Seny prekursor diubah fosfoenol piruvat,
sementara as. amino diubah  piruvat &
senyawa antara TCA , dan utk slanjutnx
diubah mjd glukosa dgn bbrp thpn reaksi
• Formasi PEP dlm jalur glukoneogenesis
bkn suatu kebalikan sederhana dr reaksi
yg bersangkutan dlm glikolisis.
 Reaksi pembentukan D-Glukosa dari bbrp senyawa prekursor

L-Prolin
L-Arginin
L-Laktat -ketoglutarat L-Glutamat
L-Histidin

L-Alanin L-Laktat
L-Serin Piruvat Suksinat L-Laktat
L-Laktat
CO2

2PEP Oksaloasetat Malat Fumarat

L-
Aspartat
D-GLUKOSA
• Ada 2 thpn reaksi yg b’beda scr enzimatis
dgn reaksi dlm glikolisis :
1. hidrolisis D-fruktosa 1,6-BP  D-fruktosa
6-P dikatalisis oleh enzm fruktosa 1,6 BP
fosfatase
2. pe glukosa-6P glukosa dikatalsis oleh
enz glukosa 6 fosfatase
• Glukogenesis diatur olh 4 enz kunci : a)
piruvat karboksilase, b) PEP karboksilase,
c) D-fruktosa 1,6 BP 1-fosfatase, d) D-
glukosa 6-fosfatase