Download Chapter 4 The Importance of High

Chapter 4
The Importance of High-Energy Bond
High energy bond: covalent bond
Food for thought: does the biosynthetic processes
violate (위반하다) thermodynamics (열역학)?
Seemingly (겉으로 보기에) yes, but actually (실제로)
not Æ input of high-energy activated (활성화된)
precursors (전구체)
Molecules that donate energy are thermodynamically unstable
-The weaker the covalent bonds, the larger the amount of free energy, and vice versa
Æ the stronger the bond, the less energy it can give off (내어놓다)
-What is the best food in terms of chemical sense: molecules that can readily (쉽게)
donate energy, contain weak covalent bonds (e.g., glucose) and are therefore
thermodynamically unstable (compare CO2 and glucose, 어느 것이 더 좋은 음식,
또는 에너지원 인가? 좋은 음식의 조건, 우리는 화학에너지를 먹고 산다!!)
-CO 2 Æ glucose in plant: need input of light energy Æ results in the formation of ATP
-even a weak covalent bond is very strong Æ need energy supply to break Æ achieve
(달성하다) activation state
-activation energy is usually less than the original bond energy, because molecular
rearrangements do not involve the production of completely (완벽히) free atoms
-activation energy ranges 20-30 kcal/mole
Æ not spontaneous at physiological
temperature Æ preventing spontaneous
rearrangement of cellular covalent bond
-all these features are important for
the existence (생존) of life
(A-B) + (C-D) Æ (A-D) + (C-B)
Keq = concA-D x concC-B / concA-B x concC-D
ΔG = -RT ln Keq or Keq = e-ΔG/RT
Figure 1. The energy of activation
Enzymes lower activation energies in biochemical reactions
-enzymes: essential for life, biocatalyst (생체촉매)
-how function: speed up the rate of chemical reaction by
lowering activation energy
-enzymes can make it achieve to the lowest free energy status
(상태) of reactants without affecting (영향을 미치다) the nature
of equilibrium (평형)
Figure 2
Free energy in biomolecules
-unstable food molecules are destined (운명짓다) to convert
into more stable and smaller molecules (e.g., CO2, water)
through degradative (붕괴적인) pathway
-Two purposes of degradative pathway (oxidative pathway)
1) produce small organic fragments (조각) necessary as building
block
2) conserve (보존하다) the free energy
(e.g., ATP: 세포내의 기축통화?)
-Food molecule Æ free energy (40 % of glucose) + heat + entropy
High-energy bonds hydrolyze with large negative ΔG
-average high energy bond: ~ 7 kcal/mole
-free energy stored in one glucose molecule is 688 kcal/mole Æ need multiple
step to completely
degrade (붕괴시키다)
the molecule
-Kinds of high-energy
bonds: all involve P or
S atoms
-ATP is the most
important P type
-acetyl-CoA is the
most important
S-type Æ main source
of fatty acid
biosynthesis
High-energy bonds in biosynthetic reaction
-construction/deconstruction vs biosynthesis/degradation
-biosynthetic pathway demand (요구하다) an external (외부의)
source (원천) of free energy
-thus, coupled with the
breakdown of a high
energy bond
-but not all steps of
biosynthesis require
the breakdown of
a high energy bond
Figure 3. multistep metabolic pathway
Peptide bonds hydrolyze spontaneously
-ΔG for the formation of dipeptide = 1 ~ 4 kcal/mole Æ not spontaneous
-but take into account the fact that the concentration of water molecule much
higher than any other cellular molecules ( >>100 times)
Amino acid(A) + amino acid (B) Æ dipeptide (A-B) +H2O
Keq = concA-B x concH2O /concA x concB
ΔG = -RT ln Keq
-relative (상대적인) concentration is very important
-in theory, proteins are unstable and will spontaneously degrade to free AA
-But this process is too slow to affect cellular mechanisms in the absence of
specific enzymes
-Thus proteins remain (유지되다) stable unless (~하지 않으면) their
degradation is not catalyzed by specific enzymes
Coupling of negative with positive ΔG
-How is the protein synthesis (having positive ΔG value of 0.5 kcal/mole
for each peptide bond) possible thermodynamically?
-Biosynthesis is almost always coupled with energy consumption (소모) of
negative ΔG (e.g., hydrolysis of ATP)
adenosine-O-P~P~P + H2O Æ adenosine-O-P~P + P (ΔG = -7kcal/mole)
adenosine-O-P~P~P + H2O Æ adenosine-O-P + P~P (ΔG = -8kcal/mole)
adenosine-O-P~P + H2O Æ adenosine-O-P + P (ΔG = -6kcal/mole)
-Peptide bond formation is coupled with the breakdown of ATP to AMP
and PP
Activation of precursors in group transfer reaction
-energy Æ heat or chemical bonds in coupled reactions,
useful when coupled or useless (소용없는) when not coupled
-coupled reaction is achieved by two or more successive (연속적인) reactions
Æ group transfer reaction, in which always involves molecular exchange
(교환) of functional groups
(A-X) + (B-Y) Æ (A-B) + (X-Y) : group transfer
(A-B) + (H-OH) Æ (A-OH) + (B-H) : hydrolysis
-group transfer involves activated molecules associated with high-energy
bonds Æ group activation
ATP + GMP Æ ADP + GDP
ATP + GDP Æ ADP + GTP
ATP versatility (다용도임) in group transfer
-ATP synthesis: a key in the controlled energy trapping in oxidative
phosphorylation & photosynthesis (ADP + P + energy Æ ATP)
-ATP is the original biological recipient of high-energy groups Æ
must be the starting point for
thermodynamically favorable (선호하는)
reactions
-contains two high-energy bonds
-high-energy quality retains (유지되다)
only when transferred
(전달하다) to an
appropriate (적당한) acceptor
(수용체) molecules
(e.g., COO~P, -C-O~P)
Figure 4
Activation of amino acids by attachment of AMP
-activation of amino acids are required (필요로하다) for the protein
synthesis
-these coupled reactions involves (~을 수반하다) the removal of activating
group and conversion (전환) of a high-energy bond into one with a lower
free energy of hydrolysis
AA + ATP Æ AA~AMP + PPi (by aminoacyl synthetase)
AA~AMP + tRNA Æ AA~tRNA + AMP
AA~tRNA + growing polypeptide (n) Æ tRNA + growing polypeptide (n+1)
Nucleic acid precursors are activated by the presence of PPi
-DNA and RNA are built up from mononucleotide (nucleoside phosphate)
-phosphodiester bond releases considerable free energy upon hydrolysis
(-6 kcal/mole) Æ mean that nucleic acids will spontaneously hydrolyze
Æ need even highly activated precursors for the synthesis
-Precursors for DNA: dATP, dGTP, dCTP, dTTP
-Precursors for RNA: ATP, GTP, CTP, UTP
Deoxynucleoside-P + ATP Æ deoxynucleoside-P~P (i.e., dNDP) + ADP
Deoxynucleoside-P~P + ATP Æ deoxynucleoside-P~P~P (i.e., dNTP) + ADP
deoxynucleoside-P~P~P + polynucleotide (n) Æ P~P + polynucleotide (n+1)
-ΔG of the reaction ~ 0.5 kcal/mole Æ what is the source of free energy
The value of P~P release in nucleic acid synthesis
-needed free energy comes from the splitting (분열) of PPi group
P~P Æ 2P (ΔG = -7 kcal/mole)
-reactions with small, positive ΔG value are often part of important metabolic
pathway in which they are followed by reactions with large negative ΔG value
-single reaction never occurs independently, rather the nature of the equilibrium
is constantly being changed through the addition and removal of metabolites
P~P splits characterize most biosynthetic reactions
-all biosynthetic reactions are characterized by one or more steps that
release P~P group (e.g., synthesis of polypeptide, polynucleotide)
-compare dNTP and dNDP as
precursors for DNA synthesis
(Fig 5)
-according to the law of mass
action, “a” reaction would
become reversible
-split of P~P provide the
driving force to forward
reaction
-Thus, (d)NTP, instead of (d)NDP,
is not a matter of chance
Figure 5