Chemistry of Carbon. Building Blocks of Life

Transcription

1 Chemistry of Carbon Building Blocks of Life

2 Why study Carbon? All of life is built on carbon Cells ~72% H 2 O ~25% carbon compounds carbohydrates lipids proteins nucleic acids ~3% salts Na, Cl, K

3 Chemistry of Life Organic chemistry is the study of carbon compounds C atoms are versatile building blocks bonding properties 4 stable covalent bonds H H C H H

4 Complex molecules assembled like TinkerToys

5 Hydrocarbons Combinations of C & H non-polar not soluble in H 2 O hydrophobic stable very little attraction between molecules a gas at room temperature methane (simplest HC)

6 Hydrocarbon diversity

7 Isomers Molecules with same molecular formula but different structures (shapes) different chemical properties different biological functions 6 carbons 6 carbons 6 carbons

8 Form affects function Structural differences create important functional significance amino acid alanine L-alanine used in proteins but not D-alanine medicines L-version active but not D-version sometimes with tragic results stereoisomers

9 L-Amino Acids are used in proteins 9

10 Form affects function Thalidomide prescribed to pregnant women in 50s & 60s reduced morning sickness, but stereoisomer caused severe birth defects

11 Semin Hematol Oct;42(4 Suppl 4):S3-8. Lenalidomide and thalidomide: mechanisms of action--similarities and differences. Anderson KC. Source: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Abstract Multiple myeloma is a B-cell malignancy characterized by an excess of monotypic plasma cells in the bone marrow. The molecular mechanisms that are involved in disease progression depend on the interaction between the multiple myeloma cells and the bone microenvironment. Because these mechanisms have been well characterized, it is possible to develop regimens that are more specific to pathways involved in the pathogenesis of multiple myeloma than is typical for conventional chemotherapy in disease management. Thalidomide and immunomodulatory drugs (IMiDs) have now been shown to block several pathways important for disease progression in multiple myeloma. First established as agents with antiangiogenic properties, thalidomide and IMiDs inhibit the production of interleukin (IL)-6, which is a growth factor for the proliferation of myeloma cells. In addition, they activate apoptotic pathways through caspase 8-mediated cell death. At the mitochondrial level, they are responsible for c-jun terminal kinase (JNK)-dependent release of cytochrome-c and Smac into the cytosol of cells, where they regulate the activity of molecules that affect apoptosis. By activating T cells to produce IL-2, thalidomide and IMiDs alter natural killer (NK) cell numbers and function, thus augmenting the activity of NK-dependent cytotoxicity. Data delineating these events have been derived from experiments done in resistant and sensitive multiple myeloma cell lines. Although thalidomide and IMiDs demonstrate similar biologic activities, IMiDs are more potent than thalidomide and achieve responses at lower doses. Lenalidomide, a thalidomide derivative, has also been shown to have a different toxicity profile. Our understanding of the mechanism of action of these agents has provided a platform for exciting clinical trials evaluating combinations of thalidomide and lenalidomide with both conventional chemotherapy and newer targeted agents. PMID: [PubMed - indexed for MEDLINE]

12 Diversity of molecules Substitute other atoms or groups around the carbon ethane vs. ethanol H replaced by an hydroxyl group ( OH) nonpolar vs. polar gas vs. liquid biological effects! ethane (C 2 H 6 ) ethanol (C 2 H 5 OH)

13 Functional groups Parts of organic molecules that are involved in chemical reactions give organic molecules distinctive properties hydroxyl carbonyl carboxyl Affect reactivity amino sulfhydryl phosphate makes hydrocarbons hydrophilic increase solubility in water

14 Viva la difference! Basic structure of male & female hormones is identical identical carbon skeleton attachment of different functional groups interact with different targets in the body different effects

15 Hydroxyl OH organic compounds with OH = alcohols names typically end in -ol ethanol

16 Carbonyl C=O O double bonded to C if C=O at end molecule = aldehyde if C=O in middle of molecule = ketone

17 Carboxyl COOH C double bonded to O & single bonded to OH group compounds with COOH = acids fatty acids amino acids

18 Amino -NH 2 N attached to 2 H compounds with NH 2 = amines amino acids NH 2 acts as base ammonia picks up H + from solution

19 Sulfhydryl SH S bonded to H compounds with SH = thiols SH groups stabilize the structure of proteins

20 Phosphate PO 4 P bound to 4 O connects to C through an O lots of O = lots of negative charge highly reactive transfers energy between organic molecules ATP, GTP, etc.

21 Macromolecules Building Blocks of Life

22 Macromolecules Smaller organic molecules join together to form larger molecules macromolecules 4 major classes of macromolecules: carbohydrates lipids proteins nucleic acids

23 Polymers Long molecules built by linking repeating building blocks in a chain monomers building blocks repeated small units covalent bonds H 2 O HO H HO H Dehydration synthesis HO H

24 How to build a polymer Synthesis joins monomers by taking H 2 O out one monomer donates OH other monomer donates H + together these form H 2 O requires energy & enzymes You gotta be open to bonding! H 2 O HO Dehydration synthesis Condensation reaction HO H HO enzyme H H

25 How to break down a polymer Digestion use H 2 O to breakdown polymers reverse of dehydration synthesis cleave off one monomer at a time H 2 O is split into H + and OH H + & OH attach to ends requires enzymes releases energy HO Breaking up is hard to do! enzyme H H 2 O Hydrolysis Digestion HO H HO H

26 Any Questions??

27 You should be able to recognize all these structures? What macromolecule is this a part of? What are the functional groups?