metabolisme selular dan regulasinya
TRANSCRIPT
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METABOLISME SELULAR
DAN REGULASINYA
Dr. Ardiana Ekawanti
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GP_Fall_20072
PENDAHULUAN
Term derived from the Greek m-,
meta-bolismos; betweeningest ion and
excret ion;
refers to theprocessing anduse of
nutrients by living organisms
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METABOLISM: encompassesALLbiochemical
reactions within a living entity.
Metabolism defines a living entity as a chemical machine.
Total metabolism: all biochemical processes within an
organism.
Cellular metabolism: all biochemical processes within a
cell.
METABOLISM enables the organism to maintain its
living state and do WORK: to breakdown, absorb
and process nutrients; to grow, divide; handle
stressors; maintain homeostasis; etc.
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Manfaat Belajar Metabolisme?
Provides information about how organisms deal with nutrients, drugs, toxic factors;
nutritional needs (malnutrition); energy balance (obesity);
pathologic states (inborn errors; metabolic imprinitng; diabetes,etc)
where/how we can intervene to fix metabolic errors whetherinborn or acquired (suggest therapies; prosthetic devices).
New interests emerge
Increased socio-economic impact of metabolic diseases:diabetes, obesity, aging
New technologies emerge: metabolomics, lipidomics, proteomics
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Metabolism Pathway
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An organisms metabolism transforms matter
and energy, subject to the laws of
thermodynamics A metabolic pathway has many steps
That begin with a specific molecule and end with a
product That are each catalyzed by a specific enzyme
Enzyme 1 Enzyme 2 Enzyme 3
A B C D
Reaction 1 Reaction 2 Reaction 3
Starting
moleculeProduct
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CATABOLIC
degradative
complexsimple
produce ATP
oxidative
(generate e-)
employ
NAD+
/NADH
ANABOLIC
synthetic (build-up)
simple complex
consume ATP
reductive (consume e-)
employ NADP+/NADPH
Intermediary Metabolism
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Catabolic Pathways
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Stages of Cellular Metabolism
STAGE 2
monomers organic
STAGE 1
polymers monomers
STAGE 3
organic inorganic
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Common Features of Metabolic Reactions
obey the universal lawsof physics: can
calculate DG
occur under mild conditions: constant
pressure (p=ct); nearly constant temperature;nearly neutral pH (6.8-7.4)
are catalyzed by biomolecules (enzymes);
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Cont
occur as step-wise in chains, orpathways,
use a small number of activated carriers(ATP,
NAD, CoA, etc) to shuttle electrons, energy or
small organic groups (acyl, malonyl, etc); ratiosindicative of cellular status
are highly regulatedto serve cellular goal with
maximal efficacy.
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Regulatory Mechanisms
ratesof metabolic reactions and levelsof specific metabolitesare precisely controlled to address cellular needs.
CELLULAR METABOLISM is controlled at several levels.
1. EnzymeA. Enzyme ACTIVITY
- substrate availability(relative to KM)
- competitive/allosteric binding(e.g. substrate level control;
feedback inhibition): fast, direct, reversible- covalent modification(e.g. phosphorylation): may be
reversed; involves signal transduction cascades;
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B. Enzyme TYPE and AMOUNT
(synthesis/degradation)
- gene transcription (enzyme isoforms,induction/repression)
- mRNA processing (splice variants), mRNA
editing; siRNA
- protein translation (speed)
- protein degradation (ubiquitination)
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Allosterism
Continuous feed-forward or feed-back control if effector ispresent
Depends on the cellular concentrations of effectors(metabolites)
Adjusts quaternary structure; the dynamic equilibrium ofnative conformations
Occurs rapidly (seconds); lasts for as long as the modulatoris present
Covalent modification (phosphorylation is most common)
Places the enzyme on stand-by or high-gear Digital-like, on/off regulation
Promoted by kinases/phosphorylases cascades (hormone-initiated)
Usually last for longer periods (minutes)
Regulation of Enzyme Activity
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Regulation of Enzyme Amount or Type
Transcriptional control: amount of type of
enzyme expressed (TF)
Translational control: rate of translation; RNA
degradation
Control of protein degradation (ubiquitination)
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Multicellular organism face the challenge tointegrate the cellular metabolism of all cells andrespond to environmental cues.
The process of transmitting this information fromoutside of the cell to inside the cell is calledsignal transduction.
Hormonal Regulation
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The extracellular messengers that carry the informationinclude:
hormones: chemicals synthesized in specialized cellswhich act on remote targets; are carried via the blood;act within an organism
growth factors: secreted proteins capable ofstimulating cellular proliferation and differentiation
neurotransmitters: chemicals used locally to relay,amplify and modulate signals between two neurons;act usually at specialized cellular junctions: synapses.
pheromones: secreted chemicals that trigger a naturalbehavioral response; usually acts between organisms.
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Mechanismis through receptor-
binding/conformational-change which result
in: Changes in transcription (steroid hormones)
Initiation of intracellular cascades (calcium, PIP,
cAMP)
GLUCAGON: hunger hormone increases intracellular
cAMP
EPINEPHRINE flight or flight hormone (stress);
increases cAMP!
INSULIN: satiety hormone; oppose the effects ofglucagon and epinephrine
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Terima Kasih