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
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