BIOMOLEKUL
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
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
Biology and Chemistry Background Biology Prokaryotes vs Eukaryotes Organelle Functions
Chemistry Bonds
• Biomolekul : Senyawa2 kimia yg secara alami hanya dite-
mukan dlm tubuh organisme atau sisa organisme setelah mati
• Atom penyusun biomolekul : C,H,O,N,S,P
• Pembagian Biomolekul : 1. Biomolekul sederhana
* Monosakarida * Asam amino * Asam lemak * Asam Nukleat •
2. Makromolekul : * Polisakarida * Polipeptida * Lemak/ Lipid
* Polinukleotida
• ORGANISME : tersusun dr senyawa organik & inorganik
• ORGANIK : - protein - karbohidrat - lipid - asam nukleat : DNA, RNA • INORGANIK : * asam * basa * garam
* H2O
• MAKROMOLEKUL KEBANYAKAN MERUPAKAN POLIMER • Contoh : Protein
rangkaian asam amino
Polisakarida
rangkaian monosakarida
monomer hidrolisis
sintesis
H2O H2O
polimer
• 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 molekul H2O
masuknya
• 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
• KARBOHIDRAT 1. Monosakarida = gula sederhana CnH2nOn ALDOSA
KETOSA
C3 Triosa
Gliserosa
Dihidroksiaseton
C4 Tetrosa
Eritrosa
Eritrolusa
C5 Pentosa
Ribosa
Ribulosa
C6 Heksosa
Glukosa
Fruktosa
Monosakarida
Disakarida
• 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 glikogen
selulosa
polimer glukosa
• 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
Amilosa
Amilopektin Struktur Amilum
Ikatan α 1,6 Glikosidik Struktur Glikogen
Sellulosa
Perbedaan Ik. α 1,4 dgn Ik. Β 1,4 Glikosidik
• 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 essensial H R-C-COONH3+
asam amino
• 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
• LIPID * sekelompok senyawa heterogen yg berhubungan 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
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
• 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
• Berdasarkan ikatan rangkap, asam lemak : 1. Asam lemak jenuh ( saturated ) - tidak ada ikatan rangkap - mis. Asam palmitat Asam stearat
C16 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
• 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 )
• 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
• 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
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
• 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 )
Coenzymes (vitamines)
Amino acids carbohydrate
hormones nucleotides
Amino acids lipids
22nd edition designed by Dr. Donald E. Nicholson
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).
(Fuels)
Exergonic Oxidation Biodegradation
Output of energy
Simpler Metabolites
Complex Metabolites
Input of energy
Endergonic Reduction Biosynthesis
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”
(Fuels)
The role of Metabolism Extract energy and reducing power
ATP: Energy currency Also for mobility, transport of nutrients and so on.
Generate all biomolecules
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).
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!
Metabolism allows the cycling of C/O and the flow of energy in the biosphere
glucose
Producers
Consumers
H2O
Metabolism also allows the cycling of N in the biosphere
(NH4+)
NO3NO2-
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
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.
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.
•
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.
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 coenzyme A in metabolism.
• 1955, Axel Hugo Theodor Theorell: nature and mode of action of oxidation enzymes“.
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.
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.