BIOCHEMISTRY

Definition:

the study of the chemistry of life

“The basic goal of the science of biochemistry is to determine how the collections of inanimate molecules that constitute living organisms interact with each other to maintain and perpetuate life.”

Lenhinger, Principles of Biochemistry

BIOCHEMISTRYFocus:

1. Biological Structures

Interaction, organization and coordination of biomolecules

Chemical and 3D structures of biomolecules

Synthesis and degradation of biomolecules

2. Metabolism

Energy production, utilization and conservation

anabolism vs catabolism

3. Genetic Information

Transmission, expression and storage of genetic information

Biology and ChemistryBackground

Biology Prokaryotes vs EukaryotesOrganelle Functions

Chemistry Bonds

BIOMOLECULES

LIFE - Chemical Evolution

Functional GroupsFunctional Groups

Functional GroupsFunctional Groups

carbohydratecarbohydrate

Amino acidsAmino acids

Coenzymes (vitamines)Coenzymes (vitamines)

Amino acidsAmino acids

hormoneshormones

nucleotidesnucleotides

lipidslipids

22nd edition designed by Dr. Donald E. Nicholson22nd edition designed by Dr. Donald E. Nicholson

metabolism is categorized metabolism is categorized into two typesinto two types

• Catabolism Catabolism ((biobiodegradationdegradation): larger ): larger molecules (nutrients and cell constituents) molecules (nutrients and cell constituents) are broken down (often via exergonic are broken down (often via exergonic reactions) to salvage (reuse) their reactions) to salvage (reuse) their components or/and to generate energy.components or/and to generate energy.

• Anabolism Anabolism ((biosynthesisbiosynthesis): The generation ): The generation of biomolecules from simpler components of biomolecules from simpler components (often via endergonic reactions). (often via endergonic reactions).

(Fuels)

Exergonic Oxidation

Complex Metabolites

Endergonic Reduction

SimplerMetabolites

BiodegradationBiodegradation

BiosynthesisBiosynthesis

Output of energyOutput of energy

Input of energyInput of energy

Major Roles of Major Roles of MetabolismMetabolism

• Extract energy and reducing power from Extract energy and reducing power from the environment (the environment (photosynthesis and photosynthesis and oxidative degradation of nutrientsoxidative degradation of nutrients).).

• Generation (interconversion) of all the Generation (interconversion) of all the biomolecules for a living organism.biomolecules for a living organism.

Thus comes the term “Dynamic Biochemistry”

(Fuels)

Extract energy and reducing power

ATP: Energy currency

Generate all biomolecules

The role of Metabolism

Also for mobility,transport of nutrients

and so on.

Classification of organisms Classification of organisms based on trophic (“feed”) based on trophic (“feed”) strategiesstrategies

• AutotrophsAutotrophs—synthesize all cellular —synthesize all cellular components from simple inorganic components from simple inorganic molecules (e.g, H2O, CO2, NH3, H2S).molecules (e.g, H2O, CO2, NH3, H2S).

• HeterotrophsHeterotrophs—Derive energy from —Derive energy from oxidation of organic compounds (made oxidation of organic compounds (made by autotrophs).by autotrophs).

Metabolism in various Metabolism in various living organisms allow living organisms allow carbon, oxygen and carbon, oxygen and nitrogen to be cycled in the nitrogen to be cycled in the biosphere.biosphere.

The cycling of matter is The cycling of matter is driven by the flow of driven by the flow of energy in one direction energy in one direction through the biosphere!through the biosphere!

Metabolism allows the cycling of C/O and the flow of energy in the biosphere

H2O

glucose

Producers Consumers

Metabolism also allows the cycling

of N in the biosphere

(NH4+)

NO3-

NO2-

General Features of General Features of MetabolismMetabolism • Occurs in specific cellular (Occurs in specific cellular (tissue and organtissue and organ) locations as a ) locations as a

series of enzyme-catalyzed linear, branched or circular series of enzyme-catalyzed linear, branched or circular reactions, or reactions, or pathwayspathways..

• Highly coupled and interconnected (“Highly coupled and interconnected (“Every road leads to Every road leads to RomeRome”).”).

• Highly regulatedHighly regulated (often reciprocally) to achieve the best (often reciprocally) to achieve the best economy (“economy (“Balanced supply and demand”Balanced supply and demand”).).

• The number of reactions is large (over 1000), however, the The number of reactions is large (over 1000), however, the number of types of reactions is relatively small (number of types of reactions is relatively small (what happens what happens in animal respiration happens in plant photosynthesisin animal respiration happens in plant photosynthesis).).

• Well Well conservedconserved during evolution: reflecting the unity of the life during evolution: reflecting the unity of the life phenomena (“phenomena (“what happens in bacteria happens in human what happens in bacteria happens in human beingbeing”).”).

General approaches for General approaches for studying metabolismstudying metabolism

• Purification and Chemical characterization Purification and Chemical characterization of metabolites;of metabolites;

• Tracing the fates of certain biomolecules Tracing the fates of certain biomolecules in living subjects (via such chemical labels in living subjects (via such chemical labels as isotopes). as isotopes).

• Isolation of genetic mutants having Isolation of genetic mutants having genetic defects. genetic defects.

• Identification and characterization of Identification and characterization of enzymes.enzymes.

Issues for current and Issues for current and future investigation on future investigation on metabolismmetabolism

• Continue to unveil new pathways and new regulation Continue to unveil new pathways and new regulation strategies of metabolism.strategies of metabolism.

• Studies on enzymes.Studies on enzymes.• Observation of metabolic processes in intact living Observation of metabolic processes in intact living

organisms (e.g., in the brains under various states)organisms (e.g., in the brains under various states)• Metabolism differences among various organisms or Metabolism differences among various organisms or

various states of the same organism (for diagnosing various states of the same organism (for diagnosing and treating such diseases as cancer, infections of and treating such diseases as cancer, infections of bacteria or viruses, obesity, etc; to understand aging).bacteria or viruses, obesity, etc; to understand aging).

• Appropriate and inappropriate nutrition.Appropriate and inappropriate nutrition.• Biotechnological application of knowledge learned from Biotechnological application of knowledge learned from

metabolic studies in medicine, agriculture and industry.metabolic studies in medicine, agriculture and industry.•

Nobel Prizes in revealing Nobel Prizes in revealing the Metabolism of living the Metabolism of living matter (1)matter (1)

• 1907, Eduard Buchner: 1907, Eduard Buchner: cell-free fermentationcell-free fermentation..• 1922, Archibald B. Hill: 1922, Archibald B. Hill: production of heat in the muscle?;production of heat in the muscle?;

Otto Meyerhof: Otto Meyerhof: fixed relationship between the fixed relationship between the consumption of oxygen and the metabolism of lactic acid consumption of oxygen and the metabolism of lactic acid in the musclein the muscle..

• 1923, Frederick Grant Banting, John James Richard 1923, Frederick Grant Banting, John James Richard Macleod: Macleod: discovery of insulindiscovery of insulin..

• 1929, Arthur Harden, Hand von Euler-Chelpin: 1929, Arthur Harden, Hand von Euler-Chelpin: fermentation of sugar and fermentative enzymesfermentation of sugar and fermentative enzymes..

• 1929, Christiaan Eijkman: 1929, Christiaan Eijkman: antineuritic vitamin;antineuritic vitamin; Sir Sir Frederick Gowland Hopkins: Frederick Gowland Hopkins: growth-stimulating vitaminsgrowth-stimulating vitamins..

• 1931, 1931, Otto Heinrich WarburgOtto Heinrich Warburg: : nature and mode of action nature and mode of action of the respiratory enzyme.of the respiratory enzyme.

Nobel Prizes in revealing Nobel Prizes in revealing the Metabolism of living the Metabolism of living matter (2)matter (2)• 1934, 1934, George Hoyt Whipple, George Richards Minot, George Hoyt Whipple, George Richards Minot,

William Parry Murphy: William Parry Murphy: liver therapy in cases of liver therapy in cases of anaemiaanaemia..

• 1937, Albert Szent-Gyorgyi: 1937, Albert Szent-Gyorgyi: biological combustion, biological combustion, vitamin C and the catalysis of fumaric acidvitamin C and the catalysis of fumaric acid..

• 1943, 1943, Henrik Carl Peter Dam: Henrik Carl Peter Dam: discovery of vitamin Kdiscovery of vitamin K;; Edward Adelbert Doisy: Edward Adelbert Doisy: chemical nature of vitamin Kchemical nature of vitamin K..

• 1947, Carl Cori and Gerty Cori: 1947, Carl Cori and Gerty Cori: catalytic conversion catalytic conversion of glycogenof glycogen; Bernardo Houssay: ; Bernardo Houssay: hormone of the hormone of the anterior pituitary lobe in the metabolism of sugaranterior pituitary lobe in the metabolism of sugar..

• 1950, 1950, Edward Calvin Kendall, Tadeus Edward Calvin Kendall, Tadeus Reichstein,Philip Showalter Hench: Reichstein,Philip Showalter Hench: hormones of the hormones of the adrenal cortex, their structure and biological effects.adrenal cortex, their structure and biological effects.

• 1953, Hans Krebs: 1953, Hans Krebs: citric acid cyclecitric acid cycle; Fritz Lipmann: ; Fritz Lipmann: role of co-enzyme A in metabolismrole of co-enzyme A in metabolism. .

• 1955, Axel Hugo Theodor Theorell: 1955, Axel Hugo Theodor Theorell: nature and mode nature and mode of action of oxidation enzymesof action of oxidation enzymes“.“.

Nobel Prizes in revealing Nobel Prizes in revealing the Metabolism of living the Metabolism of living matter (3)matter (3)

• 1961, Melvin Calvin: 1961, Melvin Calvin: carbon dioxide carbon dioxide assimilation in plantsassimilation in plants..

• 1964, Konrad Bloch, Feodor Lynen: 1964, Konrad Bloch, Feodor Lynen: cholesterol cholesterol and fatty acid metabolismand fatty acid metabolism..

• 1971, 1971, Earl W. Sutherland, Jr.: Earl W. Sutherland, Jr.: mechanisms of mechanisms of the action of hormonesthe action of hormones..

• 1978, Peter Mitchell: 1978, Peter Mitchell: chemiosmotic theory of chemiosmotic theory of biological energy transferbiological energy transfer..

• 1982, Sune K. Bergström, Bengt I. Samuelsson, 1982, Sune K. Bergström, Bengt I. Samuelsson, John R. Vane: John R. Vane: prostaglandins and related prostaglandins and related biologically active substancesbiologically active substances..

• 1985. Michael S. Brown, Joseph L. Goldstein: 1985. Michael S. Brown, Joseph L. Goldstein: regulation of cholesterol metabolismregulation of cholesterol metabolism..

Nobel Prizes in revealing Nobel Prizes in revealing the Metabolism of living the Metabolism of living matter (4)matter (4)• 1988, Sir James W. Black, Gertrude B. Elion, George 1988, Sir James W. Black, Gertrude B. Elion, George

H. Hitchings: H. Hitchings: principles for drug treatmentprinciples for drug treatment..• 1988, Johann Deisenhofer, Robert Huber, Hartmut 1988, Johann Deisenhofer, Robert Huber, Hartmut

Michel: Michel: photosynthetic reaction centrephotosynthetic reaction centre..• 1992, 1992, Edmond H. FischerEdwin G. Krebs: Edmond H. FischerEdwin G. Krebs: reversible reversible

protein phosphorylation as a biological regulatory protein phosphorylation as a biological regulatory mechanismmechanism..

• 1994, 1994, Alfred G. GilmanMartin Rodbell: Alfred G. GilmanMartin Rodbell: G-proteins G-proteins and the role of these proteins in signal and the role of these proteins in signal transduction in cellstransduction in cells..

• 1997, Paul D. Boyer, John E .Walker: 1997, Paul D. Boyer, John E .Walker: synthesis of synthesis of ATPATP..

• 1998, Robert F. Furchgott, Louis J. Ignarro, Ferid 1998, Robert F. Furchgott, Louis J. Ignarro, Ferid Murad: nitric oxide as a signalling molecule in the Murad: nitric oxide as a signalling molecule in the cardiovascular system.cardiovascular system.

Nobel Prizes in revealing Nobel Prizes in revealing the Metabolism of living the Metabolism of living matter (5)matter (5)• 1999, Gunter Blobel: 1999, Gunter Blobel: protein localizationprotein localization..• 2000, Arvid Carlsson, Paul Greengard, Eric 2000, Arvid Carlsson, Paul Greengard, Eric

R. Kandel: R. Kandel: signal transduction in the signal transduction in the nervous systemnervous system..

• 2001, Leland H. Hartwell, Tim Hunt, Sir Paul 2001, Leland H. Hartwell, Tim Hunt, Sir Paul Nurse: Nurse: regulators of the cell cycleregulators of the cell cycle..

• 2002, Sydney Brenner, H. Robert Horvitz, 2002, Sydney Brenner, H. Robert Horvitz, John E. Sulston: John E. Sulston: regulation of organ regulation of organ development and programmed cell deathdevelopment and programmed cell death. .

• 2004, Aaron Ciechanover, Avram Hershko, 2004, Aaron Ciechanover, Avram Hershko, Irwin Rose: Irwin Rose: ubiquitin-mediated protein ubiquitin-mediated protein degradationdegradation..