Metabolisme Selular Dan Regulasinya

8/12/2019 Metabolisme Selular Dan Regulasinya

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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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Metabolisme Selular Dan Regulasinya