Professional Documents
Culture Documents
&
PRINCIPLE OF ENERGY
METABOLISM
EDITED & RECOMPOSED BY
Dr. Liniyanti D.Oswari MSc.
For Medical student, Sriwijaya University
Block 8
Biological oxidation
Carbohydrate metabolism
Lipid metabolism
Protein metabolism
Gluconeogenesis
Calories
Fat contains 9 calories per gram
Protein contains 4 calories/gram
Carbohydrates has 4 calories per
gram
(approximately)
Anabolism: Building Up
Anabolism
Energy
Flows
through ATP
and redox
carriers to
couple
Catabolic
and
Anabolic
Pathways
Nonlinear Metabolic
Pathways
Metabolism in Muscle
Glucose
Glycogen
Glycogenolysis
Ca2+
PKa
Lactate
BCAA
Ile, Val
No O2
Fatty acids
Glycolysis
G6P
Pyruvate
Krebs
cycle
-Oxidation
Ca2+
PDH
Acetyl-CoA
Ca2+
ISDH, KGDH
Production of ATP
Electron
Transport
Chain
Eric Niederhoffer
Carbohydrate metabolism
Glucose
Rbc metabolism
Glycogen
Blood glucose
Diabetes
Glucose
How does the body metabolise glucose?
How can we obtain energy from glucose?
How is energy derived from glucose?
Glucose
2 types of glycolysis:
Aerobic g. and anaerobic g.
Aerobic g. occurs when oxygen supply is sufficient
Anaerobic g. occurs when oxygen supply is lacking
In aerobic g.:
Oxygen status: sufficient oxygen supply
Glucose pyruvate TCA GTP, NADH & FADH2
Substrate-level phosphorylation: GTP ATP
NADH & FADH2 ETC ATP:
1 NADH 3 ATP
1 FADH2 2 ATP
Anaerobic g.:
Oxygen status: insufficient oxygen supply
Glucose pyruvate lactate
Lactate is used via Cori cycle
Rbc metabolism
Glycogen
Branching enzyme
Straight chain enzyme
Blood glucose
Note:
Maintenance of blood
glucose
Note:
There are many factors which regulate blood glucose level
Factors: insulin, liver, glucagon, epinephrine, etc
When we eat:
At high blood glucose level, insulin is secreted
Insulin causes cells to take up glucose
Cells use glucose for energy
When we sleep:
The liver maintains blood glucose (by hepatic glycogenolysis) to
within acceptable levels between 4.2-6.2 mmol/L =70-110 mg/dl
(fasting values)
Gluconeogenesis
What is gluconeogenesis?
Figure 24.14
Protein Metabolism
Pyruvic acid
One of the keto acid intermediates of the Krebs
cycle
GLYCOGEN
Ribose-5-P
Glucos
e
Lactat
e
Glucose-6-P
b
b
PROTEIN
f
TRIACYLGLYCEROLS
Urea
Amino
Acids
Free Fatty
Acids
Pyruvate
Acetyl-CoA
m
Ketone
Bodies
o
n
ATP
Energy
The meaning of energy in energy
metabolism
In a haste to learn the individual reactions in a pathway, its
easy to lose sight of the purpose of the pathway. With energy
metabolism, the purpose is to generate energy, generally as ATP or
NADH or some high energy compound that will be used in a later
anabolic step. Glycolysis and Krebs cycle reactions have a high
number of kinase and dehydrogenase enzymes, respectively, for this
reason. This class of enzymes is intimately connected with energy
production and conservation. Pathways in the cytosol tend to be less
energy yielding, whereas those in the mitochondria are almost totally
devoted to energy production. This tutorial will bring you closer to
understanding why and how cells conserve energy. It will also help
you see the logic behind molecular energy calculations. As you listen
to your heart pump or move your arm to scratch your head, you
should be able to tell what purpose energy serves to life.
Hydrolysis
Reactions tend to
be Strongly
Favorable
(Spontaneous)
Isomerization
Reactions Have
Smaller Free
Energy Changes
Complete
Oxidation of
Reduced
Compounds is
Strongly
Favorable
Thermodynamic Laws
ADP + PO4
This means the environment of the cell gains 30.5 kJ of heat energy for each
mole of ATP hydrolyzed by water. Obviously, this is wasteful. To counter the
loss, ATP hydrolysis is coupled with the synthesis of a phosphorylated
compound. You saw this as a coupled reaction when ATP was needed to
produce glucose-6-PO4 or fructose 1,6-bisPO4 (click 1).
Glucose + ATP
Fructose-6-PO4 + ATP
Glucose-6-PO4 + ADP
Fructose 1,6-bisPO4 + ADP
Now you see that by making glucose-6-PO4 or fructose 1,6-bisPO4, the cell avoids
losing the larger part of the ATP hydrolysis energy as heat. This is energy
conservation. Click one to go on.
25 oC
100 oC
25 oC
25 oC
37 oC
25 oC
25 oC
C=O
CH2
CH3
+ ATP
2-phosphoglycerate
PEP + H2O
pyruvate + ATP + H2O
pyruvate + NADH + H+ + 2ATP + 2H2O
Removing the common terms on both sides yields a final equation (click 1).
We see that the phosphate on glyceraldehyde-3-PO4 and the inorganic PO4
both contribute to formation of ATP. Thus, 2 ATPs are formed by the 5
reactions. Under anaerobic conditions two represents the final yield. But, if
the reaction was carried out with oxygen and involved the mitochondria,
energy to the equivalent of 5 ATPs would result. Click 1 to see why.
Electron transport
H2O
NAD
ATP
ATP
ATP
NADH from the cytosol yields its electrons indirectly via a shuttle. NADH
generated by the 3 NAD-linked dehydrogenases in the Krebs cycle provide
most of the energy. For example, each citrate molecule oxidized to CO2 and
H2O generates the equivalent of 36 ATPs. Click 1 to see how this value was
obtained.
isocitrate
CO2
NADH
NADH
-ketoglutarate
malate
NADH
fumarate
succinyl-CoA
FADH2
GTP
succinate
C4H4O5 + 31/2 O2
4CO2 + 2H2O
C6H8O7 + 41/2O2
6CO2 + 4H2O
C4H6O5 + 5 O2
4CO2 + 3H2O
CO2
Thermodynamics and
Metabolism
A. Free-Energy Change
Free-energy change (G) is a measure of the
chemical energy available from a reaction
G = Gproducts - Greactants
H = change in enthalpy
S = change in entropy
B. Equilibrium Constants
and
Standard Free-Energy
ForChange
the reaction: A + B
C+D
Greaction = Goreaction + RT ln([C][D]/[A][B])
At equilibrium: Keq = [C][D]/[A][B] and
Greaction = 0, so that:
Goreaction=RTlnKeq
Go' = RT ln K'eq
Variation of equilibrium constant with Go (25 oC)
K'eq
G '
kJ/mol
10
- 23
10
- 11
10 = 1
is at equilibrium
10
-2
+ 11
10
-4
+ 23
Energy coupling
Go' = 31 kJ/mol
Coupled reaction:
ATP + glucose ADP + glucose-6-P Go' = 17 kJ/mol
The structure of the enzyme active site, from which H2O is
excluded, prevents the individual hydrolytic reactions, while
favoring the coupled reaction.
AMP~P AMP + Pi
Alternatively:
AMP~P~P AMP + P~P
P~P 2 Pi
(PPi 2Pi)
Inorganic polyphosphate
Many organisms store energy as inorganic
polyphosphate, a chain of many phosphate residues
linked by phosphoanhydride bonds:
P~P~P~P~P...
Hydrolysis of Pi residues from polyphosphate may be
coupled to energy-dependent reactions.
Depending on the organism or cell type, inorganic
polyphosphate may have additional functions.
E.g., it may serve as a reservoir for Pi, a chelator of
metal ions, a buffer, or a regulator.
Phosphocreatine (creatine
phosphate), another
compound with a "high
energy" phosphate linkage, is
used in nerve & muscle for
storage of ~P bonds.
H
N
P
O
CH3
C
NH2
O
CH2
phosphocreatine
O
C
C
CH2
PEP
O
ADP ATP
OPO32
H+
C
C
OH
CH2
enolpyruvate
CH3
pyruvate
NH2
N
ester linkage
O
-O
P
O-
O
O
P
O-
O
O
CH2
O-
adenine
O
OH
H
OH
ribose
O
6 CH
OH
P
OH
O
H
OH
3
OH
H
1
H
2
OH
CH2
OH
glucose-6-phosphate
HO
OH
CH
CH2
O
O
glycerol-3-phosphate
Protein Kinase
OH + ATP
Protein
Protein
O + ADP
O
Pi
H2O
Protein Phosphatase
Go' of phosphate
hydrolysis, kJ/mol
Phosphoenolpyruvate (PEP)
Phosphocreatine
Pyrophosphate
Glucose-6-phosphate
Glycerol-3-phosphate
Kinetics vs Thermodynamics:
A high activation energy barrier usually causes
hydrolysis of a high energy bond to be very slow in
the absence of an enzyme catalyst.
This kinetic stability is essential to the role of ATP
and other compounds with ~ bonds.
If ATP would rapidly hydrolyze in the absence of a
catalyst, it could not serve its important roles in energy
metabolism and phosphate transfer.
Phosphate is removed from ATP only when the
reaction is coupled via enzyme catalysis to some other
reaction useful to the cell, such as transport of an ion,
phosphorylation of glucose, or regulation of an enzyme
by phosphorylation of a serine residue.
Pathway
Eukaryote
Prokaryote
Glycolysis
Cytoplasm
Cytoplasm
Intermediate step
Cytoplasm
Cytoplasm
Krebs cycle
Mitochondrial
matrix
Cytoplasm
ETC
Pathway
By substratelevel
phosphorylation
By oxidative
phosphorylation
From
NADH
From
FADH
0
Glycolysis
(2X3)=6
Intermediate
step
(2X3)=6
Krebs cycle
Total
2
4
(6X3)=18
30
(2X2)=4
4
Oxidation-Reduction
It was oxidized
So the Cu was reduced!
Oxidation-Reduction
Remember:
Oxidation-Reduction
+4
+3
+2
+1
0
-1
-2
-3
-4
You Try It
Oxidized
Fe2+ Fe 3+
Reduced
OXIDIZED!
Cu 2+ Cu (s)
Hint: Cu (s) is Cu 0
REDUCED!
Oxidation-Reduction
Zn2+(aq) + 2e-
Zn is oxidized
Cu (aq) + 2e
Cu(s)
Cu2 + is reduced
Oxidation-Reduction
Zn2+(aq) + Cu(s)
Oxidation-Reduction
CH4 (g)
O2(g)
gains H;
is reduced
Oxidation-Reduction
2Fe2 O3 (s)
Oxidation-Reduction
Reactions
Reduced
organic
compounds
serve as fuels
from which
electrons can
be stripped off
during oxidation
Reversible Oxidation of a
Secondary Alcohol to a
Many biochemical oxidation-reduction reactions
Ketone
involve transfer of two electrons
In order to keep charges in balance, proton transfer
often accompanies electron transfer
In many dehydrogenases, the reaction proceeds by a
stepwise transfers of proton ( H+ ) and hydride ( :H- )
Heat of Reaction
Heat of Reaction
You should be able to complete a table to calculate energy yields from glucose or fatty acids (of any given length)
-- assuming 2.5 ATP per NADH (1.5 per glycolytic NADH) and 1.5 ATP per FADH
From glucose
Glycolysis
____ NADH x ____ ATP
____ ATP
Transition Rx
____ NADH x ____ ATP x 2 pyr
Krebs cycle
____ NADH x ____ ATP x 2 pyr
____ FADH x ____ ATP x 2 pyr
____ GTP x ____ ATP x 2 pyr
Total
ATP yield
_______
_______
_______
_______
_______
_______
30
ATP yield
_______
_______
_______
_______
_______
84
reduces cytochrome C
electron transfer CoQ to cyt C
oxidizes cytochrome C;
reduces O2 to H2O
electron transfer cyt C to O2
Lactate
e = electrons
CYTOPLASM
Glucose
NAD
O2
OUTER
MEMBRANE
e
CoQ
e
GLYCOLYSIS
FADH2
NADH
e
NAD+
Pyruvate
Dihydroxyacetone
phosphate
(DHAP)
(1)
Glycerol e
3-phosphate
INNER
MEMBRANE
MATRIX
DHAP
(2)
G3P
Glycerol-3-phosphate
dehydrogenase
FAD
e = electrons
Glucose
NAD+
GLYCOLYSIS
INNER
OUTER MEMBRANE
MEMBRANE
e-
e-
Pyruvate
NADH
e-
OAA
(6)
(1)
NAD+
eMalate
OAA
Complex I
Glu
Glu
Asp
KG
(5)
Asp
(4)
CYTOPLASM
e(3)
KG
(2)
NADH
eMalate
NAD+
MATRIX
Inner mitochondria
membrane
Mitochondrion
has two
membrane
bilayers
Matrix
Cytochrome B, Cytochrome
C, Fe-S proteins, etc.
NADH
NAD
Matrix
+
2H
ATP
Synthase
O
H2
2
O
ATP production
Summary
In this chapter, we learned that the rules of thermodynamics, and organic
Review Questions
How does muscle produce ATP
(carbohydrates, fatty acids, branched-chain
amino acids)?
What are the key Ca2+ regulated steps?
3. Is pyruvate acetyl-CoA the only way to enter carbons into the Krebs cycle?
Ans: No. Any compound that can be converted into a Krebs cycle intermediate will
contribute carbons to the Krebs cycle. This applies to aspartate and glutamate,
which form OAA and -ketoglutarate, respectively.
5. How many ATPs are generated when succinyl-CoA is oxidized in the cycle?
Ans: 30. One for GTP, two for FADH2 and 3 for NADH must be added to the 24 for 2
turns of the cycle.
Energi digunakan
700 2000
2400 2800
1300 1800
350 450
2400 2600
3100 - 3600
Aktifitas
Kkal/mnt
Duduk sambil istirahat 0.7 2.0
Berjalan
2.0 6.0
Lari cepat
15 atau lebih
Lari jarak jauh/Maraton 10 atau lebih
Balap sepeda
10 atau lebih
Meningkat:
Pertumbuhan
Badan Kurus & Tinggi
Laki-laki > Perempuan
Demam , stress
Kehamilan /menyusui.
Meningkat pada thyroxin ( Thyrotoxocosis
Total Energy(TE)
TE = BMR +TEF + Activities
Aktifitas: Apa saja kegiatan rutin
Sedentary 25-35% BMR
Light 35-50%
Moderate 50-70%
Heavy >70%
http://www.americaonthemove.org/
USATODAY.com - Study: Obesity rises faster i
n poor teens