Celullar

Metabolism
Part-1
Oleh: Heri Setiadi, M.Si
Pelatihan Pendalaman Materi
Bidang Biologi bagi Guru SMA/SMK Sederajat
Prime Park Hotel, Bandung, Jawa Barat, Indonesia
5-8 Desember 2017

QITEP In Science @qitepinscience QITEP In Science qitep_in_science

What is Metabolism ?
• The totality of an organism’s chemical
reactions is called metabolism (from the
Greek metabole, change).
• What is metabolism?
✓ How cells acquire, transform, store and
use energy
✓ Study reactions in a cell and how these
processes are coordinated and regulated
• Metabolism is an emergent property of
life that arises from orderly interactions
between molecules.
Metabolic pathways can
be linear, branched,
cyclic or spiral
Multienzyme systems arranged into
different metabolic pathways:
a) Enzymes loosely held together.
Diffusion of intermediates to other
enzyme.
b) Multienzyme complex tightly
associated. Intermediates
channeled from one active site to
the other.
c) Multienzyme system in a
membrane
Anabolism VS catabolism
The First Law of Thermodynamics
According to the first law of thermodynamics, the energy of the
universe is constant: Energy can be transferred and transformed,
but it cannot be created or destroyed. The first law is also known
as the principle of conservation of energy.
Enzyme
Major Metabolic Pathways in a
Bacterial Cell (M.Shuler, 2002)
both catabolic and anabolic pathways can be
subdivided into three stages, based on the
complexity of the metabolites (the intermediates
and products of metabolism)
• Stage 1: the interconversion of polymers and complex
lipids with monomeric intermediates
• Stage 2: the interconversion of monomeric sugars,
amino acids, and lipids with still simpler organic
compounds
• Stage 3: the ultimate degradation to, or synthesis from,
inorganic compounds, including CO2, H2O, and NH3
Three major nutrients consumed
by mammals:
(1) Carbohydrates - provide
energy
(2) Proteins - provide amino acids
for protein synthesis and some
energy
(3) Fats - triacylglycerols provide
energy and also lipids for
membrane synthesis
Review of Metabolism Pathways
http://www.genome.jp/kegg/pathway/map/map01100.html

Glucose metabolism is the centre of the cell metabolism pathways

 Glucose Catabolism
Glucose

Glycolysis or
Embden-Meyerhof-Parnas (EMP)

Aerobic metabolism Anaerobic metabolism

Fermentation: ethanol,
acetic acid, lactate.

Tricarboxylic acid (TCA)

or (Krebs) Oxidative phosphorylation
or (Citric acid cycle)
The Cori Cycle
The TCA Cycle

Figure 8.11
The Tricarboxylic Acid Cycle
• Each cycle produces
• Two carbons that are lost to CO2
• Eight hydrogen atoms and their electrons
• Small amount of energy as GTP
• Provides the starting material for creating
nonessential amino acids through transamination
The Tricarboxylic Acid Cycle
• Each cycle produces
• Two carbons that are lost to CO2
• Eight hydrogen atoms and their electrons
• Small amount of energy as GTP
• Provides the starting material for creating
nonessential amino acids through transamination
The Electron Transport Chain
• Final stage of metabolism when electrons are
transferred from one complex to another, resulting
in the formation of ATP and water
• Generates 90% of the ATP used by the body for
energy, growth, and maintenance
• Takes place in the inner mitochondrial membrane
of the cell
 Glucose Catabolism
Oxidative Phosphorylation

• In the process of Oxidative Phosphorylation

In eucaryotes:
NADH + H+ 3 ATP
FADH2 2 ATP
In procaryotes:
NADH + H+ ≤2 ATP
FADH2 ATP
 Glucose Aerobic Catabolism
Reaction Summary
• EMP (glycolysis)
Glucose + 2ADP + 2 NAD+ + 2 Pi →2 pyruvate + 2 ATP+ 2 (NADH + H+)

• Entry of pyruvate
2pyruvate + 2NAD+ + 2CoA-SH →2 acetyl-CoA + 2CO2 + 2(NADH + H+)
• TCA cycle
2acetyl-CoA + 6 NAD + 2FAD + 2GDP+ 2Pi + 4H2O → 2CoA + 6(NADH
+ H+) +2FADH2+2GTP (~ATP) + 4CO2
• Oxidative Phosphorylation
In eucaryotes
EMP: 2 NADH → 2 FADH2 → 4 ATP (glycerol phosphate shuttle)
Entry of pyruvate and TCA: 8 NADH → 24 ATP
TCA: 2FADH2 → 4 ATP
The overall reaction:
Glucose + 6O2 + 36ADP + 36 Pi → 6 CO2 + 6 H2O + 36 ATP
Transamination
• The transfer of an amino group from one amino
acid to an alpha-keto acid to form a new
nonessential amino acid
• Carbon skeleton for nonessential amino acids come
from
• Pyruvate from glycolysis
• Alpha-ketoglutarate from the TCA cycle
Transamination

Figure 8.12
 FERMENTATION
VS
ANAEROBIC RESPIRATION
 Shuttles Allow Movement Across
Mitochondrial Membranes

• The inner mitochondrial membrane

must be impermeable to most
molecules, yet much exchange has to
take place between the cytoplasm and
the mitochondria  need transporter.
• NADH cannot simply pass into
mitochondria for oxidation by the
respiratory NADH cannot simply pass
into mitochondria for oxidation by the
respiratory
• NADH cannot simply pass into
mitochondria for oxidation by the
respiratory chain, because the inner
mitochondrial membrane is
impermeable to NADH and NAD +.
How Does Protein Provide
Energy?
• Amino acids
• Primary use/most important function is building protein
• If the amino acid is not used to build protein the amine
group must be removed through deamination
• Excess can be used for energy production, converted to
glucose, or stored as fat
• Used, in a limited extent, for energy in diets low in
kilocalories and/or carbohydrate
Ketogenic verses Glucogenic
Amino Acids
• Ketogenic amino acids
• Leucine
• Lysine
• Both ketogenic and glucogenic amino acids
• Isoleucine
• Tryptophan
• Phenylalanine
• Tyrosine
• Glucogenic amino acids
• The fourteen other amino acids
Glucogenic and Ketogenic Amino Acid Metabolism

Acetyl CoA cannot be used to make glucose

Figure 8.10
Quick Review
• Amino acids can
• Be used to produce energy
• Be used to produce glucose
• Convert to fatty acids and can be stored as triglycerides
• Must be deaminated to be used for energy
• Once deaminated can be transformed into:
• Pyruvate
• Acetyle CoA
• TCA cycle compounds
• Glucogenic amino acids can be converted to
glucose
Fatty Acid Metabolism
Fatty acids in the cytosol are activated by conversion to CoA
thioesters by acyl-CoA synthetase (ATP dependent)
• Fatty acid attached to CoA-SH
• The PPi released is hydrolyzed by a pyrophosphatase to 2 P
• Net of two ATP equivalents are consumed to activate one
fatty acid to a thioester
 ATP Yield from Fatty Acid Oxidation:
Palmitic Acid (C16)
• The breakdown by an organism of 1 mol of palmitic acid requires 1 mol of ATP (for
activation) and forms 8 mol of acetyl-CoA.
• The complete degradation of 1 mol of palmitic acid requires the β-oxidation reactions to be
repeated seven times. Thus, 7 mol of NADH and 7 mol of FADH2 are produced. Reoxidation
of these compounds through respiration yields 2.5–3 and 1.5–2 mol of ATP, respectively.
The energy calculations can be summarized as follows:

1 mol of ATP is split to AMP and 2Pi −2 ATP

8 mol of acetyl-CoA formed (8 × 12 ATP)
• 3 NADH 24 NADH
• 2 CO2 x 8 16 CO2 96 ATP
• 1 ATP 8 ATP
• 1 FADH2 8 FADH2
7 mol of FADH2 formed (7 × 2) 14 ATP
7 mol of NADH formed (7 × 3) 21 ATP
Total 129 ATP