Transcript ada nosyl tionina

Bioenergetics and Biochemical Reaction types
Chapter 13
• A property of the living organism: (1) alive, (2) grow, (3) reproduce
A fundamental properties of all living
1) Ability to harness energy
organism
2) Ability to channel it into biological work
Simple precursor
Chemical energy,
photosynthetic energy
Synthesis of complex and highly
ordered marcromolecules
Movement of heart: chemical energy  concentration gradient and electrical gradient
Fireflies and deep-sea fish: chemical energy  light
• Biological energy transductions obey the same chemical and physical laws that govern all
other natural processes  to understand these laws and how they apply to the flow of
energy in the biosphere
13. 1. Bioenergetics and thermodynamics
• Bioenergetics: quantitative study of energy transductions (changes of one form of energy
into another)
1. Biological energy transductions obey the law of thermodynamics
• Two fundamental laws of thermodynamics
1) For any physical or chemical change, the total amount of energy in the universe
remains constant; energy may change form or it may be transported form one region to
another, but it cannot be created or destroyed
2) In all natural processes, the entropy of the universe increase; the universe always tends
toward increasing disorder
• Some definition (again)
1) Gibbs free energy (G): the amount of energy capable of doing work during a reaction at
constant temperature and pressure  ΔG (free energy change); joules/mole
2) Enthalpy (H): the heat content of the reacting system; reflects the number and kinds of
chemical bonds in the reactants and products  the heat content of the products is
less than that of the reactants (ΔH is a negative); joules/mole
3) Entropy (S): a quantitative expression for the randomness or disorder in a system
The units of ΔG, ΔH = joule/mole =calories/mole (1 cal =4.194 J)
The units of entropy (S) = joules/mole·Kelvin (J/mol·K)
ΔG = ΔH - T Δ S
Changes of free energy, enthalpy
and entropy are related to
each other quantitatively
Energy transform
into another
Randomness or
disorder increase
Form products
2. Cells requires sources of free energy
• Cells are isothermal systems (constant temperature system)  heat flow is not a source of
energy
• The energy that cell can and must use is free energy from chemical reaction
1) Heterotrophic cells: acquire free energy from nutrient molecules
Transform to
2) Photosynthetic cells: acquire free energy from absorbed solar radiation
ATP
3. Standard free-energy change is directly related to the equilibrium constant
• Keq: equilibrium constant
• aA + bB
cC+ dD
Keq =
[C]c [D]d
[A]a [B]b
• when equilibrium status: no driving force, no net charge change
• when not equilibrium status: move toward equilibrium, net
charge change; free energy change for the reaction
• Standard condition:
(1) 1 M concentration or 101.3 kilopascals (kPa)
(2) temperature (298 K = 25 oC)
the force deriving the system toward
equilibrium  standard free-energy
change, ΔGo
• [H+] = 1 M, pH = 0
• In biological condition = well buffered condition
at pH = 7.0; [H+] = 10-7 M,
Physical constants:
[H2O] = 55.5 M,
standard transformed constants =
2+
[Mg ] = 1 mM
standard free-energy changes
In physical condition ΔG’
o
= –RT lnK’eq
4. Actual free-energy changes depend on reactant and product concentration
• Keq: equilibrium constant
Mass-action ratio (Q)
[C]c [D]d
• aA + bB
cC+ dD Keq =
[A]a [B]b
• Actual free-energy change, ΔG = ΔG’
o
+ RT InK’eq = ΔG’
= ΔG’
o
+ RT In
o
[C]c [D]d
[A]a [B]b
+ RT In Q
• Initially reaction proceeding toward to equilibrium: ΔG = negative
• Negative of ΔG becomes less and more less, eventually zero when equilibrium is reached.
0= ΔG = ΔG’
ΔG’
o
o
+ RT In Q = ΔG’
o
+ RT In
[C]eq [D]eq
[A]eq
[B]eq
= ΔG’
o
+ RT InK’eq
= - RT InK’eq
5. Standard free-energy changes are additive
• A
ΔG1’o
B
• Glucose + Pi
• ATP + H2O
• ATP + Glucose
ΔG2’o
C
∴A
C, ΔG’
o
= ΔG1’o + ΔG2’o
Glucose-6-phosphate + H2O: ΔG’
ADP + Pi: ΔG’ o = -30.5 kJ/mol
o
= 13.8 kJ/mol
ADP + Glucose-6-phosphate: ΔG’
o
= -16.7 kJ/mol
• ΔG’
is a way of expressing the equilibrium constant for a reaction
[glucose-6-phosphate]
K’eq1 =
= 3.9 X 10-3 M-1
[glucose] [Pi]
o
K’eq2 =
[ADP] [Pi]
[ATP]
• H2O is not include this reaction because its
= 2.0 X 105 M concentration (55.5 M) is assumed to remain
uncharged by the reaction
• The equilibrium constant for the two coupled reaction
[glucose-6-phosphate][ADP][Pi]
Keq1 =
[glucose] [Pi] [ATP]
= (K’eq1)(K’eq2) = (3.9 X 10-3 M-1) (2.0 X 105 M) = 7.8 X 102
13. 2. Chemical logic and common biochemical reactions
• Most of the reactions in living cells fall into one of five general categories
1) Reactions that make or break carbon-carbon bonds
2) Internal rearrangements, isomerizations, and eliminations
3) Free-radical reactions
4) Group transfer
5) Oxidation-reduction
• Two basic chemical principles
(1) A covalent bond consists of a shared pair of electrons, and
the bond can be broken in two general ways
- Homolytic cleavage: each atom leaves the bond as a
radical, carrying one unpaired electron
- Heterolytic cleavage (more common): one atom retains
both bonding electrons
(2) many biochemical reactions involve interactions between
nucleophiles and electrophiles
- nucleophiles: functional groups rich in and capable of
donating electrons)
- Electrophiles: electron-deficient functional groups that
seek electrons)
1) Reactions that make or break carbon-carbon bonds
• Heterolytic cleavage of a C-C bond yields a carbanion and a
carbocation
Carbanions and carbocations are generally so unstable, thus
reaction intermediates can be energentically inaccessible
even with enzyme catalysts
• Carbonyl groups are particularly important in the
chemical transformations of metabolic pathways
(1) The carbon of a carbonyl group has a partial
positive charge due to the electronwithdrawing property of the carbonyl
oxygen electrophilic carbon
(2) Carbonyl group facilitate the formation of a
carbanion’s on an adjoining carbon by
delocalizing the carbanion’s negative charge
(3) A imine group can serve a similar function
(4) The capacity of carbonyl and imine groups to
delocalize electrons can be further enhanced
by a general acid catalyst or by a metal ion
such as Mg2+
Nucleophile carbonion
electrophile carbonion
• Three major class of reaction in which C-C bonds
are formed or broken
(1) Aldol condensation: a common route to the
formation of a C-C bond
(2) Claisen condensation: the carbonion is stabilized
by the carbonyl of an adjacent thioester
(3) Decarboxylation: involves the formation of a
carbanion stabilized by a carbonyl group
neucleophiles
electrophiles
• Example for carbocations in carbon-carbon bond
formation by prenyltransferase reaction in the
pathway of cholesterol biosynthesis
2) Internal rearrangements, isomerizations, and eliminations
• Intramolecular rearrangement: redistribution of electrons results in alterations of many
different types without a change in the overall oxidation state of the molecule
(1) different group in the molecule may undergo oxidation-reduction, with no net change in
oxidation state of the molecule
(2) groups at a double bond may undergo a cis-trans rearrangement
(3) the positions of double bonds may be transposed
rearrangement
Conversion of Glucose-6phosphoate to fructose-6phosphate
Isomerization
Nucleophilic
groups
Nucleophiles
(c) elimination
Ionizable groups in the
enzyme
Loss of water from an alcohol  introduction
of a C=C bond
3) Free-radical reactions
• Homolytic cleavage of covalent bond  produce free radical
1) Isomerizations that make use of adenosylcobalamin (vitamin B12) or Sadenosylmethionine
2) Certain radical-initiated decarboxylation reaction
Oxygen-independent coproporphysinogen III
oxidase catalyzes decarboxylation
3) Some reduction reaction, such as that catalyzed by ribonucleotide reductase
4) Some rearrangement reactions, such as that catalyzed by DNA photolyase
4) Group transfer reactions
• The trasnfer of acyl, glycosyl, and phosphoryl groups from one nucleophile to another is
common in living cells
1) Acyl transfer: acyl group transfer generally involves the addition of a nucleophile to the
carbonyl carbon of an acryl group to form a tetrahedral intermediate
Fig. 6-21
2) Glycosyl group transfers involves nucleophilic substitution at C-1 of a sugar ring
Fig. 6-25
3) phosphoryl group is the attachment of a good leaving group to a metabolic intermediate
to “activate” the intermediate for subsequent reaction
- inorganic orthophosphate (Pi): the ionized form of H3PO4 at neutral pH, a mixture of
H2PO4- and HPO42- inorganic pyrophosphate (PPi): P2O74• Nucleophilic substitution: attachment of a phosphoryl group to
an poor leaving group (-OH): occur in hundreds of metabolic
reactions
• Phosphorous can form five covalent bonds
•
All four phosphorous-oxygen bonds with some
double bond character. Because oxygen is
more electronegative than phosphorus, the
sharing of electrons is unequal: the central
phosphorus bears a partial positive charge and
can therefore act as an electrophile
•
A phosphoryl group (-PO32-) can be transferred
to an alcohol ( forming a phosphate ester),
or to a carboxylic acid (mixed anhydride)
•
When nucleophile attacks the electrophilic
phosphorus atom in ATP, a relatively stable
pentacovalent structure forms as a reaction
intermediate.
Kinases: enzymes that catalyze phosphoryl
group transfer
•
•
Thioalcohols (thiols): the oxygen atom of an alcohol is replaced with a sulfur atom
5) Oxidation-reduction reactions
•
•
Carbone atoms can exist in five oxidation status, depending
on the elements with which they share electrons
The transition of these status are of crucial importance in
metabolism
•
Biological reaction (commonly), a compound loses
two electrons and two hydrogen ions:
dehydrogenations (catalyzed by dehydrogenases)
•
In some biological oxidation (but not all), a carbon
atom becomes covalently bonded to an oxygen atom
(a enzyme catalyze these reaction calls oxidases)
Oxygenases: if oxygen is derived directly from
molecular oxygen (O2).
•
•
•
Oxidation reaction generally coupled with reduction
Oxidation reaction generally releases energy
Most of living cells obtain the energy needed for cellular work by oxidizing metabolic
fuels such as carbohydrates or fats
•
Many of reactions are facilitated by cofactors: coenzymes and metals
1. Biochemical and chemical equations are not identical
•
•
•
•
•
Phosphorylated compounds: can exist in several ionization status and the different
species can bind Mg2+.
Ex, at pH7 and 2 mM Mg2+, ATP exists in forms ATP4-, HATP3-, H2TAP2-, MgHATP-, Mg2ATP
Biochemical equation: ATP + H2O
ADP + Pi
+
2+
Because H and Mg is constant
Chemical equation at a pH above 8.5 in the absence of Mg2+
ATP4- + H2O
ADP3- + HPO42- + H+
ΔG’o and K’eq in this book: determined at pH7 and 1 mM Mg2+
13. 3. Phosphoryl group transfers and ATP
• Heterotrophic cells: obtain free energy in a chemical form by the catabolism of nutrient
molecules
• In this chapter, we will study here the chemical basis for the large free-energy changes
1. The free-energy change for ATP hydrolysis is large and negative
• Ionized immediately because the concentration of the direct
products of ATP hydrolysis are far below the concentrations
at equilibrium
Standard condition
• However, actual free energy of hydrolysis (ΔG) of ATP in
living cells is very different because ----
• However, actual free energy of hydrolysis (ΔG) of ATP in living
cells is very different because
(1) the cellular concentration of ATP, ADP, and Pi are not
identical
(2) ATP, ADP, and Pi concentration are much lower than the 1.0
of standard condition
(3) Mg2+ in the cytosol binds to ATP and ADP
ΔGp= ΔG’o + RT ln
(Work example: 13-2)
[ADP][Pi]
[ATP]
= -52 kJ/mol
2. Other phosphorylated compounds and thioesters also have large free
energies of hydrolysis
Immediate reaction
more stable
less stable
• The several resonance forms available to Pi stabilize this product relative to the reactant,
contributing to an already negative free-energy change
• Thioesters: a sulfur atom replaces the usual oxygen in the
ester bond
• Free energy hydrolysis for thioester and oxygen ester
Becauae of orbital
overlap in O and
C atoms
• For hydrolysis reactions with large, negative, standard free-energy changes, the products are
more stable than the reactants for one or more of the following reasons
(1) The bonds strain in reactants due to electrostatic repulsion is relieved by charge separation,
as for ATP
(2) The products are stabilized by ionization, as for ATP, acyl phosphates, and thioesters
(3) The products are stabilized by isomerization (tautomerization), as for PEP
(4) The products are stabilized by resonance, as for creatine released from phosphocreatine,
carboxylate ion released from acyl phosphates and thioesters and phosphate (Pi) released
from anhydride or ester linkages
3. ATP provides energy by group transfers, not by simple hydrolysis
• General ATP hydrolysis
• Some process do involve direct hydrolysis of ATP (or GTP)
(1) Muscle contraction (5-31)
(2) The movement of enzymes along the DNA (25-35)
(3) The movement of ribosomes along the RNA (27-30)
• The phosphate compounds found in living organisms can
be divided two groups
(1) High-energy compounds: ΔG’o : < -25 kJ/mol
(2) Low energy compounds: ΔG’o : > -25 kJ/mol
Pi, PPi, AMP
are can be
transferred
• ATP: although thermodynamically unstable, it is kinetically stable (200 to 400 kJ/mol) 
ATP does not spontaneously donate phosphoryl group to water
• Phosphoryl group donate when specific enzymes are presented  can regulate the
disposition of the energy carried by ATP
4. ATP donates phosphoryl, pyrophosphoryl, and adenylyl groups
Electrophilic targets
Nucleophilic attack: an alcohol (ROH), a carboxyl group
(RCOO-) or a phosphoanhydride (a nucleoside mono- or
diphosphate
: adenylylation
5-phosphoribosyl-1-pyrophosphate: a key
intermediate in nucleotide synthesis
Transfer of phosphoryl group to glutamate or glucose
• Hydrolysis of a-b phosphoanhydride bond: ~46 kJ/mol
• Hydrolysis of b-g phosphoanhydride bond: ~31 kJ/mol
• Adenylation: produce PPi
2 Pi: 19 kJ/mol  further energy “push” for the
Inorganic pyrophosphatase
adenylylation reaction: thermodynamically favorable reaction (ex, activation of fatty acids)
• Activation of fatty acid
(1) AMP transfer from ATP to carboxyl group of FA  Form fatty acyl adenylate and
liberating PPi: exergonic: ΔG’o = -45 kJ/mol
(2) Displaces the adenylyl group to thiol group of CoA  form thioester with fatty acid:
endergonic: ΔG’o = 31.4 kJ/mol
(3) PPi  2 Pi: -19.2 kJ/mol: total = -64.8 kJ/mol
Favorable reaction
5. Assembly of informational macromolecules requires energy
• Assembly of ordered sequences (DNA, RNA, Protein) from the monomers energy obtains
from the cleavage of a-b phosphoanhydride linkage (AMP, GMP, CMP and UMP transferred
as a transferring moieties
6. ATP energizes active transport and muscle contraction
Active transport
•
•
•
•
Transport processes are major consumers of energy
Phosphoryl group donor: ATP
Phosphoryl group transfer: to enzyme, not to substrate
Phosphorylation: induces conformational change of
enzyme
Muscle contraction
• ATP bind with head of myosin (not covalent)  dissociate
from actin  ATP hydrolysis induces conformational
change (still ADP and Pi bound tightly)  Pi release 
conformational change of the head of myosin  actin
move
7. Transphosphorylations between nucleotides occur in all cell types
• ATP: (1) cell’s energy currency and donor of phosphoryl groups
(2) primary high-energy phosphate compound produced by catabolism, in process
of glycolysis, oxidative phosphorylation, photophosphorylation (in photosynthetic
cell)
• What about others such as GTP, UTP, CTP, dATP, dGTP, dTTP and dCTP  energetically
equivalent with ATP (free energy changes associated with hydrolysis of their
phosphoanhydride linkage)
• However, phosphoryl group from ATP can be transferred to other nucleotides
Mg2+
• ATP + NDP (or dNDP)
ADP + NTP (or dNTP)
Nucleoside diphosphate kinase
Ping-pong mechanism of nucleoside diphosphate kinase
• Phosphoryl group transfer from ATP  increase ADP  muscle contraction
• Intense ATP demand  cells lowers the ADP concentration  replenish ATP by the
action of adenylate kinase
• 2ADP
Mg2+
ATP + AMP ΔG’o ≒ 0
Adenylate kinase
• Phosphocreatine (PCr = creatine phosphate): serves as a ready source (reservoir) of
phosphoryl groups for the quick synthesis of ATP from ADP
• Phosphagens: PCr-like molecules in the lower phyla organism
Mg2+
• ADP + PCr
ATP + Cr
ΔG’o = -12.5 kJ/mol
Adenylate kinase
8. Inorganic polyphosphate is a potential phosphoryl group donor
•
•
•
•
•
Inorganic polyphosphate ((polyP)n): linear polymer of Pi (p511)
Present in all organism
In yeast, polyP accumulated in vacuoles (= 200 mM)
Serve as a phosphagen (Reservoir of phosphoryl group)
The shortest polyP is PPi (n=2): can serve as the energy source for active transport of H+
in plant cells (across vacuolar membrane)
Phosphoryl group donor of
phosphofructokinase in plants
• ATP + polyPn
Mg2+
ADP + polyPn+1
Polyphosphate kinase-1 (PPK-1)
• GDP + polyPn+1
Mg2+
ΔG’o = -20 kJ/mol
Polyphosphate synthesis
GTP + polyPn
Polyphosphate kinase-2 (PPK-2)
GTP, ATP synthesis
Present in
pathogenic
bacteria
13. 4. Biological oxidation-reduction reactions
• Central feature of metabolism
1) Phosphoryl group transfer
2) Electron transfer in oxidation-reduction
• Loss of electron (oxidation), gain of electron (reduction)
• In nonphotosynthetic organism, source of electron: food
• In photosythetic oranism, source of electron: chemical compound excited by the
absorption of light
• Electrons move from various metabolic intermediates to specialized electron carriers in
enzyme-catalyzed reaction  energy release
1. The flow of electrons can do biological work
• Electromotive force (emf): In battery, because the two chemical species differ in their
affinity for electrons, electrons flow spontaneously through the circuit, driven by a force
proportional to the difference in electron affinity
• Living cells have an analogous biological “circuit”, with relatively reduced compound
such as glucose (the source of electron donor)
• Glucose  enzymatically oxidized  release electron  spontaneously flow through
electron-carrier intermediates to another chemical species, such as O2: exergonic reaction
because O2 has a higher affinity for electrons than do electron-carrier intermediates
• In the mitochondrion, membrane-bound enzymes couple electron flow  a production of
transmembrane pH difference and a transmembrane electrical potential  accomplish
osmotic and electrical work
• Thus, the proton potential has potential energy: electron-motive force
• ATP synthetase: use electron-motive force to produce ATP from ADP + Pi
- Bacterial flagellar motion: use proton-motive force
2. Oxidation-reductions can be described as half-reactions
• Fe2+ + Cu2+
Fe3+ + Cu+
(1) Fe2+
(2) Cu2+ + e-
Fe3+ + eCu+
Two half-reaction
Electron donor: reducing agent
Electron acceptor: oxidizing agent
Conjugate redox pair
The oxidation of reducing sugar by cupric acid (Fig. 7-10)
R-COH + 4OH- + 2Cu2+
(1) R-COH + 2OH(1) 2Cu2+ + 2e- + 2OH-
R-COOH + Cu2O + 2H2O
R-COOH + 2e- + H2O
Cu2O + H2O
Doubled cupric to cuprous take balance the overall equation
3. Biological oxidations often involve dehydrogenation
“Owns”: more electronegative atom
O is more electronegative. Thus O
is the “owns”.
This means that C loss electron 
undergone oxidation
The carbon in living cells exists in a
range of oxidation status
Electronegativity:
H<C<S<N<O
oxidation
• Alkane: -CH2-CH2Alkene: -CH=CHOxiation = dehydrogenation
Enzymes that catalyze oxidation call dehydrogenase
reduction
• 6H+ + 6e- + N2
2NH3
**Electrons are transferred from one molecule to another in one of four ways
1) Directly as electrons: Fe2+/Fe2+ redox pair can transfer an electron to the Cu/Cu2+ redox
pair
• Fe2+ + Cu2+
Fe3+ + Cu+
2) As hydrogen atoms: hydrogen atom consists of a proton (H+) and a single electron (e-)
• AH2
A + 2 e- + 2HHydrogen/electron donor
AH2/A: conjugate redox pair  can reduce another compound B
AH2 + B
A+ + BH2
3) As a hydride ion (:H-)
Has two electrons
This reaction occurs in NAD-linked dehydrogenase
4) Through direct combination with oxygen
R-CH3 + 1/2O2
R-CH2-OH
Oxygen covalently incorporated into product:
Electron donor
Electron acceptor
4. Reduction potentials measure affinity for electrons
• When two conjugate redox pairs are together in solution, electron transfer may proceed
spontaneously depended on the relative affinity of the electron acceptor of each redox
pair for electrons  measure of this affinity (volts): Standard reduction potential (Eo)
Standard half reference of the half reaction:
H+ + e1/2H2
5. Standard reduction potentials can be used
to calculate free-energy change
• Electrons tend to flow to the half-cell with the
more positive E  the strength ΔE (difference
in reduction potential)  free energy change
ΔG = ΔE
ΔE
or
ΔG
’o
= -n
￡
ΔG = -n
ΔE
’o
￡
When acetaldehyde is reduced by the biological electron carrier NADH, ΔG = -35.3 kJ/mol
6. Cellular oxidation of glucose to carbon dioxide requires specialized electron
carriers
• The principles of oxidation-reduction energetics  can apply to the many metabolic
reactions that involve electron transfers
• Glucose oxidation:
• C6H12O6 + 6O2
kJ/mol need
6CO2 + 6H2O,
ΔG
’o
= -2,840 kJ/mol > ATP synthesis in cells: 50-60
• Cells does not convert to CO2 in a single, high energy releasing reaction but rather in a
series of controlled reactions, some of which are oxidation for the ATP synthesis from ADP
through NAD+ and FAD
coenzyme
7. A few of coenzymes and proteins serve as universal electron carriers
• NAD, NADP, FMN and FAD: water-soluble coenzymes and undergo reversible oxidation
and reduction in many of the electron-transfer reactions of metabolism
- NAD and NADP: move rapidly from one enzyme to another
- Flavin nucleotides (FMN, FAD): usually very tightly bound to the enzymes (=flavoproteins)
 serve as prosthetic group
- Lipid-soluble quinones (ubiquinones and plastoquinone): act as a electron carriers and
proton donors in the nonaqueous evironment of membranes
- Iron sulfur protein and cytochromes: serve as electron-carriers in many oxidationreduction reactions
8. NADH and NADPH act with dehydrogenase as soluble electron carriers
• NAD: nicotinamide adenine dinucleotide  NAD+: oxidized form
• NADP: nicotinamide dinucleotide phosphate (close analog of NAD)
• Oxidized form has positive charge in
nitrogen atom
• Reduction produces a new, broad
absorbance with a maximum at 340 nm
• Total concentration of NAD+ + NADH in most tissues: 10-5 M
- Concentration ration: NAD+ > NADH  favoring hydride transfer from a substrate to
NAD+ to form NADH  function in oxidation  occur in mitochondrial matrix
• Total concentration of NADP+ + NADPH in most tissues: 10-6 M
- Concentration ration: NADP+ < NADPH  favoring hydride transfer from NADPH to a
substrate  function in reduction  occur in cytosol
• More than 200 enzymes are known to catalyze reactions in which NAD+ (or NADP+)
accepts a hydride ion from a reduced substrate or NADPH (or NADH) donates a hydride
ion to an oxidized substrate
Oxidized substrate
• General reaction
• AH2 + NAD+
• A + NADPH + H+
• CH3CH2OH + NAD+
ethanol
A + NADH + H+
AH2 + NADP+
reduced substrate
oxidoreductase
CH3CHO + NADH + H+
acetaldehyde
• When reduction
NAD+ or NADP+  NADH or NADPH
Hydride ion is transferred to A or B side
Front side
Back side
Have specificity, not both
- ex, yeast alcohol dehydrogenase: A side
transfer
- B side transfer
• Most dehydrogenases:
- Contain a conserved domain called the Rossmann fold
- Rossmann fold: consists with a six-stranded parallel b
sheet and four associated a helics
- Rosssmann fold serves as binding with a cofactor
• The association between dehydrogenases and cofactor is
loose  the coenzyme readily diffuse from one enzyme
to another  act as a water-soluble carrier of electron
form one metabolite to another
(1) Glyceraldehyde 3-phosphate + NAD+
(2)
Acetaldehyde + NADH + H+
Glyceraldehyde 3-phosphate + Acetaldehyde
3-phosphoglycerate + NADH + H+
ethanol + NAD+
3-phosphoglycerate + ethanol
In overall reaction, there is not net production or consumption of NAD+ or NADH  no
concentration change of NAD+ or NADH and recycle repeatedly NAD+ or NADH.
9. Dietary deficiency of Niacin, the vitamin form of NAD and NADP, causes
pellegra
• Most coenzyme: derived from vitamins
• NAD and NADP: derived from vitamin niacin (=nicotinic
acid)
• Human cannot synthesize sufficient quantities of niacin
• Maize: content low tryptophan
• Niacin deficiency: affects all the NAD(P)-dependent
dehydrogenase  causes the serious human disease
pellagra (=rough skin): characterized by the Three Ds
(dermatitis, diarrhea and dementia)  death
• Too much alcohol drink  reduce niacin
absorption from the intestine
10. Flavin nucleotides are tightly bound in flavoproteins
•
•
•
Flavoproteins  derived
Fully reduced: 360 nm
Partially reduced: 450 nm
Fully oxidized: 370 and 440 nm
from the vitamin riboflavin
• The fused ring structure of the flavin nucleotide
(isoalloxazine ring):
• Cryptochromes (light receptor): a flavoprotein act as a (1) mediate the effects of blue light
on plant development and (2) the effects of light on mammalian circadian rhythms