Introduction to Introduction to MetabolismMetabolism

ObjectivesObjectives

Understand the concept of metabolic Understand the concept of metabolic pathwaypathway

Identify types & characters of metabolic Identify types & characters of metabolic pathways- anabolic and catabolicpathways- anabolic and catabolic

Identify ATP as the energy currency of cellsIdentify ATP as the energy currency of cells

Understand the transport of major Understand the transport of major metabolic fuel- Glucosemetabolic fuel- Glucose

MetabolismMetabolism

All the chemical reactions taking All the chemical reactions taking place inside a cell are collectively place inside a cell are collectively known as known as METABOLISMMETABOLISM

MetabolismMetabolismMetabolic Pathways areMetabolic Pathways are chemicalchemical

reactionsreactions organized in organized in multistepsmultisteps sequencessequences where: where:

The product of one reaction of the pathway The product of one reaction of the pathway serves as substrate of the subsequent serves as substrate of the subsequent reactionreaction

Most pathways can be classified as Most pathways can be classified as anabolicanabolic (synthetic) or (synthetic) or cataboliccatabolic (degenerative) (degenerative)

Integrated pathways= Integrated pathways= MetabolismMetabolism

Glycolysis, an example of a metabolic pathwayGlycolysis, an example of a metabolic pathway

Basic functions of metabolismBasic functions of metabolism

1.1. To obtain energy from fuel molecules To obtain energy from fuel molecules

2.2. To convert nutrients into precursors of To convert nutrients into precursors of cellular components.cellular components.

3. To assemble precursors utilizing energy 3. To assemble precursors utilizing energy into cellular components. into cellular components.

ANABOLICANABOLIC CATABOLICCATABOLIC

Biosynthetic Degradative

Reductive Oxidative

Energy Required Energy Liberated

Diverging Converging

Decomposition of large complex molecules into small molecules

large complex organic molecules are constructed from small molecules

Catabolism

Many Few

Anabolism Few Many(converging)

(diverging)

Catabolic PathwayCatabolic Pathway

Anabolic PathwayAnabolic PathwayCombine small moles as a.a. to form complex Combine small moles as a.a. to form complex

as ptnas ptnIt is a divergent process w needs ATP It is a divergent process w needs ATP

(endergonic) & reducing power (mostly (endergonic) & reducing power (mostly NADPH)NADPH)

Nutrients Carbohydrates Fats Proteins

End products H2O, CO2, NH3

Catabolism(oxidative, exergonicexergonic)

Macromolecules Proteins Polysaccharides Lipids Nucleic acids

Precursor Molecules Amino acids Sugars Fatty acids Nitrogenous bases

Anabolism (reductive,

endergonicendergonic)

Chemical energy

ATPNADPH

NADPH

NADPH

GTP

ATP

ATP

NADH

Catabolism and anabolism are always related.

Amphibolic PathwayAmphibolic Pathway

Amphi = Dual, amphibolic: dual pathwayAmphi = Dual, amphibolic: dual pathway

For example,For example,

Krebs cycle is mainly a Krebs cycle is mainly a cataboliccatabolic cycle, cycle, but with some but with some anabolicanabolic features, features,

e.g.,e.g., part of Krebs cycle is used for the part of Krebs cycle is used for the synthesis of glucose from amino acidssynthesis of glucose from amino acids

Therefore, Therefore, Krebs cycle is amphibolicKrebs cycle is amphibolic

Metabolic MapMetabolic Map

Different pathways can intersect, Different pathways can intersect, forming an integrated and forming an integrated and purposeful network of chemical purposeful network of chemical reactions reactions ““The Metabolic Map”The Metabolic Map”

Chemical energyChemical energy

ATP - energy currency. ATP - energy currency. It serves as the It serves as the driving force for nearly all biochemical driving force for nearly all biochemical processesprocesses

NADH,NADPH - reducing power.NADH,NADPH - reducing power.

NADH NADH for oxidation and energy yielding. for oxidation and energy yielding.

NADPH for biosynthetic processes NADPH for biosynthetic processes

ATP is the energy currency of the cellATP is the energy currency of the cell

ATP + HATP + H22O ADP +PO ADP +Pii

The free energy liberated in the The free energy liberated in the hydrolysis of ATP is used to drive the hydrolysis of ATP is used to drive the endergonic reactionsendergonic reactions

ATP is formed from ADP and PATP is formed from ADP and Pii when when fuel molecules are oxidizedfuel molecules are oxidized

This This ATP-ADP cycleATP-ADP cycle is the is the fundamental mode of energy exchange fundamental mode of energy exchange in biological systemsin biological systems

Δ Gº -7.3 kcal/mol/bond

E-rich compounds e.g.,

Oxidation

E-rich

reduced coenzymes

ETC

OxidationOxidation:Loss of hydrogenLoss of electrons

ReductionReduction:Gain of hydrogenGain of electrons

Oxidation/ReductionOxidation/Reduction

NAD/NADHNAD/NADH

Metabolism RegulationMetabolism Regulation

Intracellular RegulationIntracellular Regulation

Imp. for moment-to-moment regulation of Imp. for moment-to-moment regulation of metabolism which elicit rapid responsesmetabolism which elicit rapid responses by: by:

availability of substrateavailability of substrateproduct inhibition or product inhibition or alteration in the levels of allosteric activators or alteration in the levels of allosteric activators or

inhibitorsinhibitors

Intercellular RegulationIntercellular Regulation

Provides long-range integration of Provides long-range integration of metabolismmetabolism

Usually is Usually is slower thanslower than intracellular signals, it intracellular signals, it is done by : is done by : surface to surfacesurface to surface

the most important is the most important is chemical signaling by chemical signaling by hormoneshormones or or

neurotransmittersneurotransmittersThis results in the production of second This results in the production of second

messengersmessengers

Metabolic FuelMetabolic FuelCarbohydrates & lipids Carbohydrates & lipids (mainly) (mainly) and and

proteins proteins (little extent) (little extent) are used for are used for energy productionenergy production

These are- These are- glucose, fatty acids and glucose, fatty acids and amino acidsamino acids

GlucoseGlucose is the major metabolic fuel of is the major metabolic fuel of most tissuesmost tissues

Na+-Monosaccharide Cotransporter:Against concentration gradientEnergy dependentCarrier-mediatedCoupled to Na+ transportSmall intestine, renal tubules & choroid plexus

Na+-Independent Facilitated Diffusion: With concentration gradient Energy IndependentGlucose Transporters (GLUT 1-14)

• Tissue-specific expression pattern GLUT-1 RBCs and brainGLUT-2 Liver, kidney & pancreasGLUT-3 NeuronsGLUT-4 Adipose tissue & skeletal

muscleGLUT-5 Small intestine & testesGLUT-7 Liver (ER-membrane)

• Functions:GLUT-1, 3 & 4 Glucose uptake from bloodGLUT-2 Blood & cells (either direction)GLUT-5 Fructose transport

Take Home MessageTake Home Message

Metabolism is the sum of all Metabolism is the sum of all biochemical pathways that occur biochemical pathways that occur inside the cells.inside the cells.

A metabolic pathway is a multistep A metabolic pathway is a multistep sequences of enzyme-catalyzed sequences of enzyme-catalyzed reactionsreactions..

Catabolism is a convergent process that Catabolism is a convergent process that provides energy to cells in the form of ATP.provides energy to cells in the form of ATP.

Anabolism is a divergent process that Anabolism is a divergent process that consumes energy for the synthesis of consumes energy for the synthesis of complex molecules.complex molecules.

Metabolic pathways are tightly regulated Metabolic pathways are tightly regulated and highly integratedand highly integrated..

ATP is the energy currency of the cellsATP is the energy currency of the cells

Glucose is transported in/out of the cells Glucose is transported in/out of the cells by: by:

Energy-dependent active transportEnergy-dependent active transport

Energy-independent facilitated Energy-independent facilitated transporttransport