BIOMOLEKUL BIOCHEMISTRY Definition: the study of the chemistry of life “The basic goal of the science of biochemistry is to determine how the collections.

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2 BIOMOLEKUL

3 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

4 BIOCHEMISTRY Focus: 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

5 Biology and Chemistry Background Biology Prokaryotes vs Eukaryotes Organelle Functions Chemistry Bonds

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14 Biomolekul : Senyawa2 kimia yg secara alami hanya dite- mukan dlm tubuh organisme atau sisa orga- nisme setelah mati Atom penyusun biomolekul : C,H,O,N,S,P

15 Pembagian Biomolekul : 1. Biomolekul sederhana * Monosakarida * Asam amino * Asam lemak 2. Makromolekul : * Polisakarida * Polipeptida * Polinukleotida

16 ORGANISME : tersusun dr senyawa organik & inorganik ORGANIK : - protein - karbohidrat - lipid - asam nukleat : DNA, RNA INORGANIK : * asam * basa * garam * H2O

17 MAKROMOLEKUL KEBANYAKAN MERUPAKAN POLIMER Contoh : Protein rangkaian asam amino Polisakarida rangkaian monosakarida monomer hidrolisis sintesis H2O polimer

18 SINTESIS : ikatan yg menghubungkan 2 unit molekul terbentuk dgn. lepasnya H + dr 1 molekul penyusun dan OH - dr molekul berikutnya terbentuk H2O HIDROLISIS : putusnya ikatan antar unit molekul masuknya molekul H2O

19 BIOMOLEKUL dibagi menjadi 2 yaitu : 1. STRUKTURAL : penyusun jaringan/tubuh organisme Contoh : kolagen, keratin 2. FUNGSIONAL : untuk melaksanakan fungsi fungsi kehidupan Contoh : enzim, hormon, DNA, RNA, ATP

20 KARBOHIDRAT 1. Monosakarida = gula sederhana CnH2nOn ALDOSA KETOSA C3 Triosa Gliserosa Dihidroksiaseton C4 Tetrosa Eritrosa Eritrolusa C5 Pentosa Ribosa Ribulosa C6 Heksosa Glukosa Fruktosa

21 Disakarida Monosakarida

22 2. Disakarida ( Cn(H2O)n-1 * Sukrosa : Glukosa + Fruktosa * Laktosa : Glukosa + Galaktosa * Maltosa : Glukosa + Glukosa 3. Oligosakarida : 2-6 monosakarida 4. Polisakarida : >> monosakarida Contoh : tepung dekstrin polimer glukosa glikogen selulosa

23 Tepung ( Amilum ) * rantai lurus : ikatan (1-4)α glikosidik * sedikit rantai cabang : ikatan (1-6)α gliko sidik Glikogen : - strukturnya sama dgn amilum - rantai cabang lebih banyak Sellulosa : * tidak dapat dicerna (pd mamalia, manusia) * tidak bercabang * ikatan (1-4) β glikosidik

24 Amilosa Amilopektin Struktur Amilum

25 Ikatan α 1,6 Glikosidik Struktur Glikogen

26 Sellulosa

27 Perbedaan Ik. α 1,4 dgn Ik. Β 1,4 Glikosidik

28 PROTEIN * tersusun dari asam amino asam amino dasar untuk menyusun protein : 20 * dari 20 asam amino dasar, separuhnya tidak dapat disintesis di dalam tubuh hewan & manusia shg. hrs diperoleh dr makanan asam amino essensial H R-C-COO - NH3 +

29 ASAM AMINO PENYUSUN PROTEIN Essensial Non essensial Arginin Alanin Histidin Aspartat Isoleusin Asparagin Leusin Sistein Metionin Glutamat Fenilalanin Glutamin Threonin Serin Triptofan Tirosin Valin Prolin Hidroksiprolin

30 LIPID * sekelompok senyawa heterogen yg berhu- bungan dgn asam lemak, sifatnya : 1. relatif tidak larut dlm air 2. larut dlm pelarut non polar : eter, kloroform, benzen Macam2 lipid : 1. Lemak netral : TG = Triasilgliserol Contoh : mentega/margarin, minyak goreng Jaringan lemak terutama t.d. : T.G. 2. Fosfolipid 3. Kolesterol & steroid

31 Lipid individual tidak termasuk makromolekul 1. Triasilgliserol (TG) 2. Kolesterol 3. Fosfolipid Kandungan energi : tinggi Sumber asam lemak essensial Sumber vitamin yg larut dlm lemak : A,D,E,K

32 ASAM LEMAK : asam monokarboksilat * rantai pendek ( atom C < 6 ) * rantai medium ( atom C 8 – 14 ) * rantai panjang ( atom C > 14 ) Secara biologis yg banyak biasanya : asam lemak rantai lurus, jumlah atom C genap ( 16-20) Pemberian nama : * gugus –COOH diberi nomor 1 atau * gugus –COOH tanpa simbol, atom C disebelahnya : Cα β,γ dstnya

33 Berdasarkan ikatan rangkap, asam lemak : 1. Asam lemak jenuh ( saturated ) - tidak ada ikatan rangkap - mis. Asam palmitat C16 Asam stearat C18 - akhiran : … + anoat (-anoic) - jika rantainya panjang, p.u. bersifat padat pd suhu kamar - Asam palmitat C16 (C15H31COOH) / CH3(CH2)14COOH = asam heksadekanoat = hexadecanoic acid

34 ASAM LEMAK TAK JENUH ( UNSATURATED ) * ≥ 1 ikatan rangkap * akhiran : -enoat ( enoic ) * yg alami : umumnya berbentuk Cis (sis) cair pd suhu kamar * asam lemak tak jenuh banyak terdapat pd minyak tumbuhan ( kec. Minyak kelapa yg banyak mengandung asam lemak jenuh )

35 TG ( TRIASILGLISEROL ) * t.d Gliserol dan asam lemak dalam sel p.u. jumlah atom C : 16/18 per molekul asam lemak O O CH2-O-C-R1 R2-C-O-C O CH2-O-C-R3 * Sifat T.G. t.u. ditentukan oleh asam lemak yg dikandungnya

36 PURIN & PIRIMIDIN * Senyawa heterosiklik yg mengandung N atau disebut BASA N : Basa purin : Adenin (A) Guanin (G) Basa pirimidin : Timin (T) Sitosin (C) Urasil (U) * Nukleosida = Basa N + gula * Nukleotida = Basa N + gula + fosfat = nukleosida + fosfat

37 Basa Ribonukleosida RiboNukleotida A=Adenin Adenosin Adenilat = AMP G=Guanin Guanosin Guanilat = GMP U=Urasil Uridin Uridilat = UMP C=Sitosin Sitidin Sitidilat = CMP Basa Deoksiribonukleosida Deoksiribonukleotida A Deoksiadenosin Deoksiadenilat G Deoksiguanosin Deoksiguanilat T=timin Deoksitimidin Deoksitimidilat C Deoksisitidin Deoksisitidilat A----T G-----C

38 PERANAN NUKLEOTIDA : 1. Bahan baku DNA & RNA (polinukleotida) 2. ATP bentuk energi yg utama 3. Nukleotida adenin merupakan komponen 3 koenzim utama : NAD, FAD, KoA 4. Nukleotida sbg regulator metabolik Mis. cAMP ( mediator kerja bbrp hormon ) ATP ( mengubah aktivitas sejumlah enzim dgn modifikasi kovalen )

39 carbohydrate Amino acids Coenzymes (vitamines) Amino acids hormones nucleotides lipids 22nd edition designed by Dr. Donald E. Nicholson

40 metabolism is categorized into two types Catabolism (biodegradation): larger molecules (nutrients and cell constituents) are broken down (often via exergonic reactions) to salvage (reuse) their components or/and to generate energy. Anabolism (biosynthesis): The generation of biomolecules from simpler components (often via endergonic reactions).

41 (Fuels) Exergonic Oxidation Complex Metabolites Endergonic Reduction Simpler Metabolites Biodegradation Biosynthesis Output of energy Input of energy

42 Major Roles of Metabolism Extract energy and reducing power from the environment (photosynthesis and oxidative degradation of nutrients). Generation (interconversion) of all the biomolecules for a living organism. Thus comes the term “ Dynamic Biochemistry ”

43 (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.

44 Classification of organisms based on trophic (“feed”) strategies Autotrophs—synthesize all cellular components from simple inorganic molecules (e.g, H2O, CO2, NH3, H2S). Heterotrophs—Derive energy from oxidation of organic compounds (made by autotrophs).

45 Metabolism in various living organisms allow carbon, oxygen and nitrogen to be cycled in the biosphere. The cycling of matter is driven by the flow of energy in one direction through the biosphere!

46 Metabolism allows the cycling of C/O and the flow of energy in the biosphere H2OH2O glucose ProducersConsumers

47 Metabolism also allows the cycling of N in the biosphere (NH 4 + ) NO 3 - NO 2 -

48 General Features of Metabolism Occurs in specific cellular (tissue and organ) locations as a series of enzyme-catalyzed linear, branched or circular reactions, or pathways. Highly coupled and interconnected (“Every road leads to Rome”). Highly regulated (often reciprocally) to achieve the best economy (“Balanced supply and demand”). The number of reactions is large (over 1000), however, the number of types of reactions is relatively small (what happens in animal respiration happens in plant photosynthesis). Well conserved during evolution: reflecting the unity of the life phenomena (“what happens in bacteria happens in human being”).

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50 General approaches for studying metabolism Purification and Chemical characterization of metabolites; Tracing the fates of certain biomolecules in living subjects (via such chemical labels as isotopes). Isolation of genetic mutants having genetic defects. Identification and characterization of enzymes.

51 Issues for current and future investigation on metabolism Continue to unveil new pathways and new regulation strategies of metabolism. Studies on enzymes. Observation of metabolic processes in intact living organisms (e.g., in the brains under various states) Metabolism differences among various organisms or various states of the same organism (for diagnosing and treating such diseases as cancer, infections of bacteria or viruses, obesity, etc; to understand aging). Appropriate and inappropriate nutrition. Biotechnological application of knowledge learned from metabolic studies in medicine, agriculture and industry.

52 Nobel Prizes in revealing the Metabolism of living matter (1) 1907, Eduard Buchner: cell-free fermentation. 1922, Archibald B. Hill: production of heat in the muscle?; Otto Meyerhof: fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle. 1923, Frederick Grant Banting, John James Richard Macleod: discovery of insulin. 1929, Arthur Harden, Hand von Euler-Chelpin: fermentation of sugar and fermentative enzymes. 1929, Christiaan Eijkman: antineuritic vitamin; Sir Frederick Gowland Hopkins: growth-stimulating vitamins. 1931, Otto Heinrich Warburg: nature and mode of action of the respiratory enzyme.

53 Nobel Prizes in revealing the Metabolism of living matter (2) 1934, George Hoyt Whipple, George Richards Minot, William Parry Murphy: liver therapy in cases of anaemia. 1937, Albert Szent-Gyorgyi: biological combustion, vitamin C and the catalysis of fumaric acid. 1943, Henrik Carl Peter Dam: discovery of vitamin K; Edward Adelbert Doisy: chemical nature of vitamin K. 1947, Carl Cori and Gerty Cori: catalytic conversion of glycogen; Bernardo Houssay: hormone of the anterior pituitary lobe in the metabolism of sugar. 1950, Edward Calvin Kendall, Tadeus Reichstein,Philip Showalter Hench: hormones of the adrenal cortex, their structure and biological effects. 1953, Hans Krebs: citric acid cycle; Fritz Lipmann: role of co- enzyme A in metabolism. 1955, Axel Hugo Theodor Theorell: nature and mode of action of oxidation enzymes“.

54 Nobel Prizes in revealing the Metabolism of living matter (3) 1961, Melvin Calvin: carbon dioxide assimilation in plants. 1964, Konrad Bloch, Feodor Lynen: cholesterol and fatty acid metabolism. 1971, Earl W. Sutherland, Jr.: mechanisms of the action of hormones. 1978, Peter Mitchell: chemiosmotic theory of biological energy transfer. 1982, Sune K. Bergström, Bengt I. Samuelsson, John R. Vane: prostaglandins and related biologically active substances. 1985. Michael S. Brown, Joseph L. Goldstein: regulation of cholesterol metabolism.

55 Nobel Prizes in revealing the Metabolism of living matter (4) 1988, Sir James W. Black, Gertrude B. Elion, George H. Hitchings: principles for drug treatment. 1988, Johann Deisenhofer, Robert Huber, Hartmut Michel: photosynthetic reaction centre. 1992, Edmond H. FischerEdwin G. Krebs: reversible protein phosphorylation as a biological regulatory mechanism. 1994, Alfred G. GilmanMartin Rodbell: G-proteins and the role of these proteins in signal transduction in cells. 1997, Paul D. Boyer, John E.Walker: synthesis of ATP. 1998, Robert F. Furchgott, Louis J. Ignarro, Ferid Murad: nitric oxide as a signalling molecule in the cardiovascular system.