Académique Documents
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Prepared'by:'Robert'Paul'S.'Lim,'RPh
UNIT%EXPECTED%OUTCOMES
At the end of the lecture, the student must be able to:
1. Define and use correctly the terms intermediary or
primary metabolism, catabolism, anabolism,
pathway, feedback, committed step, ATP,
phosphoanhydride, phosphoester, CoA, thioester,
pantothenic acid, nicotinamide, niacin, NADH,
NADPH, pellagra, Flavin, FADH2, FMNH2,
riboflavin, and flavoprotein.
UNIT%EXPECTED%OUTCOMES
At the end of the lecture, the student must be able to:
2. explain the main stages in catabolism.
1. Although*many*reactions*are*near*equilibrium,*an*
entire*metabolic*pathway—and*the*cell’s*
metabolism*as*a*whole—never*reaches*
equilibrium. (?)*
2. Metabolic*pathways*proceed,*as*if*trying*to*reach*
equilibrium*but*they*cannot*get*there*because*
new*reactants*keep*arriving*and*products*do*not*
accumulate.*
! Le*Chatelier’s Principle
Mechanisms,of,Regulation
1. ALLOSTERIC,CONTROL
FEEDBACK,REGULATION
FEEDFORWARD,REGULATION
Mechanisms*of*Regulation
2.*COVALENT*MODIFICATION
Mechanisms*of*Regulation
3. GENETIC CONTROL
• Enzyme concentrations, and hence enzyme
activities, may be altered by protein synthesis in
response to metabolic needs.
• The processes of transcribing a gene to
messenger RNA and then translating the RNA to a
polypeptide chain offer numerous points for
regulation.
1. The reactants that originate the process
2. The end products, regardless of being formed in
intermediate reactions or the final reaction
3. The branching points, i.e., steps where the sequence of
reactions may follow different courses.
4. The irreversible reactions.
5. The specific reactions that are catalyzed by enzymes that are
finely regulated and so have the ability to highly accelerate
segments of the metabolism, or not.
• The metabolism is “fed” by A and has K, F, and J as “end
products.”
• An external source of G may also lead to the formation of J
and F, but not K.
• An external source of D can only lead to the formation of F.
However, if ED is not present or not operative, F will not be
formed in any circumstance.
• Likewise, if EB2 is not present or not operative, K, G, H, J, and
I will not be formed even in the presence of high
concentration of B.
• If EB1 and EB2 are never active or inactive at the
same time, F is always formed but not J;
• the reactions’ scheme assures the permanent
formation of F but the selective formation of J when
the control of the reaction course is performed by
alternate states of activity of EB1 and EB2.
MAJOR&PATHWAYS&IN&CELLS
Metabolic*Pathways*Occur*in*
Specific*Cellular*Locations
ENERGY&
RELATIONSHIPS&
BETWEEN&
CATABOLIC&AND&
ANABOLIC&
PATHWAYS
OVERVIEW'OF'ANABOLIC'PATHWAY
OVERVIEW'OF'CATABOLIC'PATHWAY
FOUR%STAGES%OF%CATABOLISM
Stage&1:&Digestion
Stage&1:&Digestion&of&proteins
Stage&1:&Digestion&of&proteins
Stage&1:&Digestion&of&Lipids
Stage&1:&Digestion&of&Lipids
Stage&1:&Digestion&of&Lipids
Stage&2:&Formation&of&Acetyl&
CoA
Stage&3:&The&Citric&Acid&Cycle
STAGE&4:&The&Electron&Transport&Chain&and&
Oxidative&Phosphorylation
MAJOR&TYPES&OF&REACTION
Major&Types&of&Reaction
1. Oxidation7reduction
2. Reactions that make or break carbon–
carbon bonds;
3. Internal rearrangements, isomerizations,
and eliminations;
4. Group transfers;
5. Free radical reactions
OXIDATION(REDUCTION
• The carbon atoms in biological molecules can
assume different oxidation states depending on
the atoms to which they are bonded.
• a carbon atom bonded to less electronegative
hydrogen atoms is least oxidized.
• a carbon atom bonded to highly electronegative
oxygen atoms is most oxidized.
OXIDATION(REDUCTION
OXIDATION(REDUCTION
Reactions*that*make*or*break*
carbon–carbon*bonds
Reactions*that*make*or*break*
carbon–carbon*bonds
Reactions*that*make*or*break*
carbon–carbon*bonds
Reactions'that'make'or'break'
carbon–carbon'bonds
ALDOLASE REACTION
CITRATE'SYNTASE'
REACTION
ACETOACETATE'
DECARBOXYLASE'
REACTION
Early&Steps&in&Cholesterol&
Biosynthesis
Internal(rearrangements,(Isomerizations,(
and(Eliminations
Internal(rearrangements,(Isomerizations,(
and(Eliminations
Internal(rearrangements,(Isomerizations,(
and(Eliminations
Group$transfers
• The$transfer$of$acyl,$glycosyl,$and$phosphoryl$groups
from$one$nucleophile$to$another$is$common$in$living$
cells.$
• Acyl$group$transfer$generally$involves$the$addition$of$
a$nucleophile$to$the$carbonyl$carbon$of$an$acyl$group$
to$form$a$tetrahedral$intermediate.
Group&transfers:&Acyl&group
Group&transfers:&Glycosyl
Group&transfers:&Phosphoryl&
• play a special role in metabolic pathways.
• General theme in metabolism: the
attachment of a good leaving group to a
metabolic intermediate to “activate” the
intermediate for subsequent reaction.
GroupGtransfers:GPhosphorylG
Better Leaving groups in BetterGLeavingGgroupsGinG
Nucleophilic Substitution: NucleophilicGSubstitution:
• Inorganic orthophosphate • inorganic pyrophosphate
(the ionized form of (P2O74D, abbreviated PPi);
H3PO4 at neutral pH, a • esters and anhydrides of
mixture of H2PO4D and phosphoric acid are
HPO42D) effectively activated for
• commonly abbreviated Pi reaction.
Group&transfers:&Phosphoryl&
Group&transfers:&Phosphoryl
Free,Radical,Reactions
RIBONUCLEOTIDE,REDUCTASE
ATP$AND$ENERGY$PRODUCTION
ADENOSINE(TRIPHOSPHATE
ATPFandFADP
• Hydrolysis of ATP cleaves one phosphate group,
forming ADP and hydrogen phosphate, HPO42–,
often abbreviated as Pi (inorganic phosphate).
This reaction releases 7.3 kcal/mol of energy.
ATP?and?ADP
• The reverse reaction, phosphorylation, adds a
phosphate group to ADP, forming ATP.
• Phosphorylation requires 7.3 kcal/mol of energy.
ATP$and$ADP
CONVENTIONSCINCWRITINGC
REACTIONS
• The principal organic reactants and products are
drawn from left to right with a reaction arrow as
usual, but additional compounds like ATP and ADP
are drawn on a curved arrow.
COENZYMES)IN)METBOLISM
COENZYMES
REDOX:'DEFINITION'OF'TERMS
Oxidizing agent
• oxidant