Biochemistry 1st Semester 1st Year PDF

BIOCHEMISTRY Prof. Anthony B. Rapista PRELIMS TOPIC OUTLINE Primary Areas of Biochemistry I. PRELIMS...

BIOCHEMISTRY Prof. Anthony B. Rapista PRELIMS TOPIC OUTLINE Primary Areas of Biochemistry I. PRELIMS Structural and Functional Chemical Structures and 3D Biochemistry arrangements of molecules. Introduction to Organic Chemistry and BioChemistry A. Biochemistry: Origin of Life Informational Biochemistry Language for storing biological B. Foundations of Biochemistry data and for transmitting that C. Applications and Significance of Biochemistry in data in cells & organisms. the Medical field D. Classification of Organic Compound Bioenergetics The flow of energy in living E. IUPAC Naming System organisms and how it is Structure and Properties of Functional Groups transferred from one process A. General Properties of each Functional Groups to another. B. Importance of each Functional Group; C. Basic IUPAC Naming of Each Functional Group Organic and Biochemical Reactions A. Organic vs. Biochemical Reactions B. Organic and Biochemical Reactions involving Functional Groups II. MIDTERMS Carbohydrates A. Functions and Classifications of Carbohydrates B. Stereoisomers of Carbohydrates Biochemistry and Life C. Fischer and Haworth Projections D. Biologically Important Carbohydrates E. Reactions of Monosaccharides All living things make use of the same types of F. Acidic Polysaccharides biomolecules, and all use energy G. Glycoproteins Lipids A. Functions of Lipids B. Physical Properties of Fatty Acids C. Structure and Classification of Lipids D. Biological Membranes E. Membrane Proteins F. The Function of Membranes G. The Lipid-Soluble Vitamins Amino Acids and Peptides Levels of Structural Organization in the Human Body A. Amino acids: Structure and Properties B. Ionization of Amino Acids C. Peptide Bonds D. Peptides with Physiological Activity IV. REFERENCES V.TRANS AUTHORSHIP I. Introduction to Organic Chemistry and Biochemistry A.BIOCHEMISTRY: ORIGIN OF LIFE What is Biochemistry?: The application of chemistry B. FOUNDATIONS OF BIOCHEMISTRY to the study of biological processes at the cellular and Cellular Foundations molecular level. Chemical Foundations DRINK | 1  Physical Foundations nucleus: DNA Genetic & Evolutionary Foundations present but not CELLULAR FOUNDATIONS separate from the rest of cell Cell Membrane Present Present Generalized Structure of the Cell Mitochondria None; enzymes Present for oxidation reactions located on plasma membrane Endoplasmic None Present Reticulum Ribosomes Present Present Chloroplasts None; Present in green photosynthesis is plants. localized in chromatophores Nucleus Contains genetic material - DNA and associated proteins. Nucleus is membrane-bounded Plasma Membrane Tough and flexible lipid bilayer. Selectively permeable to polar substances. Includes membrane proteins that function in transport, in signal receptions and as enzymes. Classification of Prokaryotes depending of the Cytoplasm Aqueous cell contents and habitats: suspended particles, and -AEROBIC:needs oxygen organelles. -ANAEROBIC:Nitrates, sulfate, CO2, and CH4 A Comparison of Prokaryotes and Eukaryotes CHEMICAL FOUNDATIONS Cellular make up of living organisms are mostly organic compounds (biomolecules) ORGANELLE PROKARYOTE EUKARYOTE Nucleus No definite Present 2  The development of new drugs involves chemical analysis and synthesis of new compounds. Clinical laboratory testing uses a wide variety of chemical techniques and instrumentation for analysis. All nursing students must be good at pharmacology in order to be able to administer the right drugs to patients. ORIGIN OF BIOCHEMISTRY FUNCTIONAL GROUPS - Group of atoms that show characteristic of physical & chemical properties. VITALISM - the idea that substances and processes associated with living organisms do not behave according to the known laws of physics and chemistry. EVIDENCES: Only living things have a high degree of complexity Only living things extract, transform and utilize energy from their environment Only living things are capable of self-assembly and self-replication. -1944 Avery, MacLeod, and McCarty identified DNA as information molecules -1953 James Watson (still alive) and Francis Crick proposed the structure of DNA -1958 Crick also proposed the central dogma of molecular biology MACROMOLECULES Protein Enzyme, structural function, Lecturer Surname, Lecturer Initials. (Year). Title of transport, signal Lecture. (Powerpoint Presentation or Audio transduction, etc. Recording). FEU-NRMF Nucleic Acids (DNA & Storage and transmission of D. CLASSIFICATION OF ORGANIC COMPOUND RNA) genetic information Polysaccharides Energy storage ORGANIC CHEMISTRY The branch of chemistry that deals with carbon Lipids Constituent of membrane compounds and energy storage Over 16 million carbon-containing compounds are known Because the C-C single bond (348 kJ/mol) and the PHYSICAL FOUNDATIONS C-H bond (412 kJ/mol) are strong, carbon compounds are stable. No equilibrium Dynamic steady state THE CARBON ATOM Exchange energy and matter Carbon forms stable, covalent bonds with other Energy conservation carbon atoms. Enzymes promotes sequences of chemical reactions Carbon atoms form stable bonds with other elements, such as: Oxygen, Nitrogen, Sulfur, and Halogen. GENETIC AND EVOLUTIONARY FOUNDATIONS Carbon atoms form double or triple bonds Carbon can form chains and rings Mutation - Provides opportunity for evolution Chemical Evolution - Generation of organic compounds under primitive atmospheric conditions Biological Evolution - photosynthetic bacteria and multicellular eukaryotes C. Applications of Biochemistry in Medical Field PROPERTIES OF ORGANIC COMPOUNDS 3  - Could be classified into two: Alicyclic Compounds, and Aromatic Compounds - Alicyclic Compounds:Compounds ORGANIC COMPOUNDS INORGANIC COMPOUNDS with a benzene-like structure that Bonding is almost entirely Most have ionic bonds exhibits aromaticity. Examples are: covalent Cyclobutane and cyclopentane. - Aromatic May be gases, liquids, or Most are solids with high Compounds:Compounds with a solids with low melting melting points benzene-like structure that exhibits points (less than 360° C) aromaticity. Example is benzene. - Heterocyclic Compounds:Compounds Most are insoluble to water Many are soluble in water where the ring contains carbon atoms along Most are soluble in organic Almost all are insoluble in with at least one other element (e.g., solvents such as diethyl organic solvents nitrogen, oxygen, sulfur). ether, toluene, and dichloromethane HYDROCARBONS Aqueous solutions do not Aqueous solutions conduct ➔ Groups of compounds where all organic compounds conduct electricity electricity are derived ➔ Made up of only hydrogen and carbon Almost all are flammable Very few compounds can easily burn TYPES OF HYDROCARBONS Reactions are usually slow Reactions are very fast ALIPHATIC Do not contain the benzene CLASSIFICATIONS OF ORGANIC COMPOUNDS group, or the benzene ring AROMATIC Contain one or more benzene rings. Organic compounds are classified by two: Acyclic & Cyclic ACYCLIC Compounds - These compounds have an open chain structure, meaning the carbon atoms FORMULAS USED IN ORGANIC CHEMISTRY are arranged in a straight or branched chain. - Saturated Compounds: Compounds where Molecular Formula: Lists kind and number of each all the carbon-carbon bonds are single type of atom in a molecule, and no bonding pattern. bonds (C-C). For example: Ethane (C₂H₆) EXAMPLE:C2H6, C3H8 - Unsaturated Compounds:Compounds Extended Structural Formula: Unambiguously containing double (C=C) or triple bonds shows how the atoms are bonded together (C≡C) between carbon atoms. Example:Ethene (CH₂ = CH₂) (double bond) and Ethyne (CH ≡ CH) (triple bond). CYCLIC Compounds - These compounds form a ring structure, where the carbon atoms are connected in a loop. - Carbocyclic Compounds:Compounds in which the ring is made up of only carbon atoms. 4  Condensed structural formulas: Bonds are omitted, repeated groups put together, side chains put in brackets. ○ Example: CH3CH2CH2CH2CH2CH3 or CH3CH(CH3)CH2CH3 ISOMERS Skeletal formula (line structural formula): Structural/Constitutional isomers: compounds with the Shorthand representation of molecule’s bonding every same molecular formula but different structure “corner” or “point of intersection” represents a carbon (arrangement of atoms). -Hydrogen atoms are implied Different isomers are completely different compounds Have different physical properties such as melting Rules for Naming Hydrocarbons point and boiling point. ➔ Find the longest continuous chain of carbon atoms. Always remember the following prefix to name the chain. - If it’s an alkane, add -ane at the end - If it’s an alkene, then add -ene at the end - If it’s an alkyne, add the ending -yne ➔ Number the carbon atoms in the chain so the lowest CYCLOALKANES possible numbers will be given for the attached side groups. Have one or more rings of carbon atoms. General formula: CnH2n or (CH2)n Although a cycloalkane has two fewer hydrogen atoms than the equivalent alkane. TYPE OF FORMULA STRUCTURAL LINE CYCLOPROPANE ALKANES Have the general formula CnH2n+2 where n=1, 2… Only single covalent bonds are present. CYCLOBUTANE Known as saturated hydrocarbons because they contain the maximum number of hydrogen atoms that can bond with the number of carbon atoms present. Have similar chemical properties Have physical properties that vary in a regular manner as the number of carbon atoms increases 5  CYCLOHEXANE 5 Carbon Chain Pentane ALKENES Alkyl groups are classified according to the number of carbons attached to the carbon atom that joins the Unsaturated hydrocarbons (olefins) contain at least alkyl group to a molecule. one carbon-carbon double bond All continuous chain alkyl groups are primary groups General formula: CnH2n Isopropyl and sec-butyl are secondary group The simplest alkene is C2H4, ethylene Used in the synthesis of many plastics and commercially important alcohols The numbers in the names of alkenes refer to the lowest numbered carbon atom in the chain that is part of the C=C bond of the alkene. An ALKYL GROUP is an alkane with one hydrogen atom removed. It is named by replacing the -ane of the alkane name with -yl. Names and Formulas of the First Five Continuous-Chain ALKYNES Alkyl Groups Alkyl Group Structure Name Unsaturated hydrocarbon that contain at least one carbon-carbon triple bond. —CH3 Methyl General formula: CnH2n-2 Ethyne (Acetylene gas) is commonly used in welding —CH2CH3 Ethyl torches —CH2CH2CH3 Propyl —CH2CH2CH2CH3 Butyl —CH2CH2CH2CH2CH3 Pentyl The numbers in the names of alkenes refer to the lowest numbered carbon atom in the chain that is part of the C=C bond of the alkene E. IUPAC NAMING SYSTEM IUPAC NOMENCLATURE – BRANCHED HYDROCARBONS 1. The base or parent name for an alkane is determined by the longest continuous chain of carbon atoms in the formula. - The longest chain may bend and twist, it is seldom horizontal - Any carbon groups not part of the base chain 2. Number the carbon atoms in the chain starting from the end are called branches or substituents with the first branch (lowest possible location of the substituent). If both branches are equally from the ends, continue until a point of difference occurs 6  4. Draw the structural formula (line or expanded) II.STRUCTURE AND PROPERTIES OF FUNCTIONAL 3. Write each of the branches/substituents in alphabetical GROUPS order before the base/stem/parent name (longest chain). Halogens usually come first ➔ FUNCTIONAL GROUPS - an atom or group of atoms Indicate the position of the branch on the main chain within a molecule that tends to exhibit similar by prefixing its name with the carbon number to which chemical properties. it is attached Separate numbers and letters with a hyphen Separate two or more numbers with commas 4.When a branch/substituent occurs more than once, prefix the name with di, tri, tetra, etc. Then list the number of the carbon branch for that substituent to the name with a separate number for each occurrence Separate numbers with commas BENZENE STRUCTURE (AROMATIC) Modern concept of benzene structure is based on overlapping orbitals ALKYLHALIDES Each carbon is bonded to two others by sharing a pair of electrons Haloalkanes contain halogen substituents which are These same carbon atoms also each share a pair of fluorine, chlorine, bromine, and iodine. electrons with a hydrogen atom IUPAC NAMES: BENZENES DRAWING STRUCTURES USING IUPAC NAME Most simple aromatic compounds are named as derivatives of benzene Example: Draw the structural formula for 1-bromo-4- For monosubstituted benzenes, name the group and methylhexane add “benzene” 1. Begin by drawing the 6-carbon parent chain, showing the 4 bonds to each carbon: 2. Add the substituents: Some members of the benzene family have unique names acquired before the IUPAC system was adopted that are still frequently used today 3. Add in H atoms to complete the structure 7  Toxic, can cause blindness and death if ingested Can be used as a fuel BENZENE COMPOUNDS Polynuclear Aromatic Composed of two or more Hydrocarbons (PAHs) aromatic rings joined together. Many have been shown to cause ➔ ETHANOL (CH3CH2OH) cancer. An odorless and colorless liquid Widely used as a solvent Heterocyclic Aromatic Rings that contain at least one The alcohol in alcoholic beverages Compounds atom other than carbon (usually Derived from the fermentation of O, N, and S) carbohydrates Beverage produced varies with the starting PHYSICAL PROPERTIES OF ALCOHOLS material and the fermentation process ➔ 2-PROPANOL (Isopropyl alcohol) (CH3CHOHCH3 ) General Structure: ROH Colorless, but has a slight odor Presence of the hydroxyl group (-OH) Commonly called rubbing alcohol IUPAC name: change the –e from the hydrocarbon Used as disinfecant, astringent and industrial name and add the suffix –ol solvent ➔ 1, 2-ETHANEDIOL (Ethylene glycol) (CH2OHCH2OH) Used as automobile antifreeze Has a sweet taste, but is extremely poisonous Added to water Lowers the freezing point Raises the boiling point ➔ PHYSICAL PROPERTIES OF ALCOHOLS - Colorless at room temperature, 4-10 carbon atoms are oily and have a heavier fruity odor - R-O-H has a structure similar to that of water - High boiling points relative to their molar masses due to the ability to hydrogen bond ➔ SOLUBILITY WITH WATER - Alcohols with 1 to 4 carbons are miscible in ➔ 1,2, 3-PROPANETRIOL (Glycerol) water (CH2OHCHOHCH2OH) - As the number of OH groups increases, the Very viscous, thick polarity, and the water solubility also Has a sweet taste increases Non-toxic - As molar mass increases, alcohols become Highly water soluble immiscible in water Used in cosmetics, pharmaceuticals, - HOCH2CH2CH2CH2OH is very miscible in lubricants, esterification of fatty acids water Obtained as a by-product of fat hydrolysis - Diols and triols are more soluble than those with only a single hydroxyl group PHENOL DERIVATIVES IMPORTANT ALCOHOLS Phenols - compounds in which the hydroxyl group is attached to a benzene ring. ➔ METHANOL (CH3OH) - Polar compounds due to the hydroxyl group Colorless and odorless liquid - Simpler phenols are somewhat water soluble Used as a solvent - Components of flavorings and fragrances 8  - Phenols have the formula Ar-OH - Widely used in healthcare as germicides, antiseptics, disinfectants. PHYSICAL PROPERTIES OF ETHERS General Structure: ROR’ Presence of the alkoxy group (-O-) IUPAC name: add the suffix –oxy to the shortest carbon chain (substituent) and name the longest parent chain based on the hydrocarbon prefixes Have lower melting and boiling points than alcohol Little association by hydrogen bonding Lower solubility in water and have the nauseating Ethers are slightly polar due to the polar C=O bond aroma Do not hydrogen bond to one another as there are no A defensive spray of North American striped skunk –OH groups (less soluble in water but soluble in Onions and garlic organic solvents such as alcohol, benzene, and acetone) EXAMPLES OF THIOLS Ethers have much lower boiling points than alcohols due to the lack of hydrogen bonding ➔ Cysteine- a non-essential amino acid important for MEDICAL USES OF ETHERS making protein, and for other metabolic functions. ➔ Ethers are often used as anesthetics. ➔ Glutathione is an antioxidant found in our body cells ➔ Accumulate in the lipid material of nerve cells ➔ 2-butene-1-thiol is found in the defensive spray of interfering with nerve impulse transmission the skunk ➔ Today halogenated ethers are used routinely as ➔ 2-propanethiol (allyl mercaptan) is found in the general anesthetics breath of people who have eaten garlic ➔ Less flammable ➔ Furfurylthiol contributes to the aroma of fresh coffee. ➔ Safer to store and to work with PHYSICAL PROPERTIES OF CARBOXYLIC ACIDS General Structure: RCOOH Presence of the carbonyl (C=O) adjacent to a hydroxyl (-OH) group (carboxyl group –COOH) IUPAC name: change -e from the hydrocarbon name and add the suffix –oic plus the word ‘acid PHYSICAL PROPERTIES OF THIOLS General Structure: RSH Presence of the sulfhydryl group (-SH) Called ‘sulfanyl’ or ‘mercapto’ as a substituent IUPAC name: The name is based on the longest alkane chain with the suffix –thiol position indicated by a number Low molar mass carboxylic acids 9  - Sharp, sour taste Lactic Acid Bacteria in mild - Unpleasant aromas produce lactic High molar mass carboxylic acids acid as a product - Fatty acids important in biochemistry of the Low molar mass carboxylic acids are water soluble due to fermentation of hydrogen bonding with: sugars Water Each Other Due to carboxylic acids forming intermolecular hydrogen bonds, boiling points are at higher temperatures than those of any other functional group studied Acid chlorides are derivatives of carboxylic acids having the general formula: RCOCl Named: by replacing the –oic acid ending of the IUPAC name with –oyl chloride PROPERTIES OF ACID CHLORIDES Noxious, irritating chemicals requiring great care in handling CARBOXYLIC ACID DERIVATIVES Slightly polar, boiling near the corresponding carbonyl’s temperature React violently with water Benzoic acid derivatives are commonly used as Widely used in the production of pesticides, plastics, antibacterial and antifungal preservatives and as and polymers flavoring agents in food, cosmetics, hygiene, and pharmaceutical products. PROPERTIES OF ESTERS More complex carboxylic acids are found in a variety of foods General Structure: RCOOR’ Derived from the reaction of carboxylic acids and Citric Acid Found in citrus alcohols fruits Presence of the carbonyl (C=O) adjacent to the alcohol derivative (-OR’) IUPAC name: use the alkyl name of the alcohol chain and change the suffix –oic of the carboxylic acid chain to –oate Tartaric Acid Used in baking powder because it will react with carbonates in the dough Form from the reaction of a carboxylic acid with an alcohol. Boiling point is lower than alcohols and carboxylic acid, cannot form hydrogen bonds, and small chains Malic Acid Gives a sour taste are soluble in water. to green apples Most have pleasant odors (fruity scents) such as raspberry, banana, pear, apple, and pineapple PROPERTIES OF ALDEHYDES AND KETONES ALDEHYDES General Structure: RCHO Presence of the carbonyl (C=O) at the terminal side of the hydrocarbon structure 10  IUPAC name: change –e from the hydrocarbon name amines, the symbol N- is added to the alkyl name of and add the suffix –al to the parent chain. the shortest substituents. KETONES General Structure: RCOR’ Presence of the carbonyl (C=O) in between hydrocarbon structure Derived from ammonia (NH3 ), have a rotting fish IUPAC name: change –e from the hydrocarbon name smell, basic in nature, and small aliphatic amines are and add the suffix – one to the parent carbon chain miscible in water. Amines up to 6 carbons long are (indicate the position of the carbonyl group) water soluble due to this hydrogen bonding Water solubility decreases as the length of the hydrocarbon portion of the molecule increases Amines form hydrogen bonds but not as strongly as alcohols Nitrogen is less electronegative than oxygen Tertiary amines cannot hydrogen bond to each other Amines have higher boiling points than alkanes and Aldehydes and ketones are polar compounds ethers but less than alcohols The carbonyl group is polar Tertiary amines have lower boiling points than the 1 ° The oxygen end is electronegative or 2 °amines of similar molecular weight Aldehydes and ketones cannot form intermolecular hydrogen bonds However, water can form hydrogen bonds with them Carbonyl groups boil at higher temperatures than hydrocarbons and ethers while at lower temperatures than alcohols MEDICALLY IMPORTANT AMINES IMPORTANT ALDEHYDES Ampethamines Stimulate the central nervous system Methanal (Formadelyde) A gas used in aqueous solutions as formalin to Analgesics (Pain relievers) and preserve tissue anesthetics (pain blockers) Ethanal (Acetaldehyde) Produced from ethanol in the liver causing hangover Decongestants Shrink the membranes symptoms lining the nasal passages Propanone (Acetone) Simplest possible ketone Sulfa Drugs The first chemicals used Miscible with water to fight infections are Flammable also made from amines Both acetone and methyl ethyl Heterocyclic Amines Cyclic ketone(butanone) are very versatile solvents compounds that have at PROPERTIES OF AMINE least one N in the ring General Structure: RNH2 Many are Derived from ammonia (NH3 ) physiologically active and Presence of the amino group (- NH2 ) many are IUPAC name: add the suffix – amine to the parent critical in carbon chain (longest). For secondary and tertiary 11  biochemistry Alkaloids Naturally occurring compounds with one or more nitrogen-containing heterocyclic ring. Examples are nicotine and morphine Acetaminophen Tylenol, Paracetamol, PROPERTIES OF AMIDES Panadol used as an aspirin substitute. It acts to reduce General Structure: RCONH2 fever and pain. Derived from the reaction of carboxylic acids and amines Barbiturates Depressant drugs used to Presence of the carbonyl (C=O) and amino (-NH2 ) induce sleep, release tension, and treat seizure groups disorder and severe trauma IUPAC name: add the suffix – amide to the parent in the skull. carbon chain (C=O) and the substituents are always attached in the amino group (NH2 ) SUMMARY OF FUNCTIONAL GROUPS Formed in a reaction between a carboxylic acid derivative and an amine or ammonia The amide bond is the bond formed between: Carbonyl group from the carboxylic acid Amino group from the amine or ammonia Most amides are solids at room temperature due to internal hydrogen bonding They are not bases A resonance structure shows why the N lone pair is unavailable to accept a proton Strong intermolecular hydrogen bonding between the III. Organic and Biochemical Reactions N-H bond of one amide and the C=O bond of another A.Organic vs. Biochemical Reactions Very high boiling points as compared to amines and other hydrocarbons and functional groups of similar Organic Reactions Biochemical Reactions length Simple amides are quite soluble in water Substitution Reaction Dehydration Synthesis and Hydrolysis IMPORTANCE OF AMIDES Elimination Reaction Phosphorylation and Hyrdrolysis A protein is a polymer of amino acids linked by the amide bonds Addition Reaction Phosphorylation and During protein synthesis, as the amino group and the Decarboxylation carboxyl group link, water is lost Radical Reaction Oxidation and Reduction Oxidation-Reduction Reaction 12 B. ORGANIC AND BIOCHEMICAL REACTIONS INVOLVING FUNCTIONAL GROUPS HALOGENATION Nitration (Substitution reaction) – replaces H atom Alkanes (Substitution reaction) – replacement of one atom with a nitro group on the ring. for a halogen atom. Alkenes (Addition reaction) the addition of a molecule of halogen (X2) to a carbon-carbon double bond to produce an alkane. REACTIONS INVOLVING ALCOHOLS Oxidation of Alcohols: ❖ In organic systems changes may be tracked: Oxidation Reduction HYDROGENATION Gain of oxygen Loss of oxygen Alkenes (Addition reaction) – addition of a molecule of Loss of hydrogen Gain of hydrogen hydrogen (H2) to a carbon-carbon double bond to produce an alkane Oxidation of Primary & Secondary Alcohols Hydrogenation of Oils to produce Margarine - Alcohols are oxidized to produce any of the following products: aldehyde, ketone and carboxylic acid. POLYMERIZATION OF ALKENES Addition Polymers of Alkenes – polymers are Hydration (Addition reaction) – addition of water to macromolecules composed of repeating units called the carbon-carbon double bond of an alkene monomers produces an alcohol. Hydrogenation (Addition/Reduction reaction) – BENZENE REACTIONS Addition of hydrogen to the carbonoxygen double Halogenation (Substitution reaction) – replaces H bond of an aldehyde or ketone produces an alcohol atom with a halogen atom (either Br or Cl). 13  The thiol-disulfide redox pair controls a critical factor in protein structure called a disulfide bridge Two cysteine molecules (amino acids) can undergo oxidation to form cystine Forms a new bond called a disulfide bond Biological Oxidation-Reduction - NAD+ is a coenzyme commonly involved in biological oxidation/reduction reactions - Oxidation of alcohols catalyze by the liver enzymes result to different physiological effects on the body - Formaldehyde causes coagulation of proteins in the cells. DISULFIDE FORMATION & INSULIN STRUCTURE - Acetaldehyde is oxidized to acetic acid, a normal constituent of a cell REACTIONS OF ETHERS Chemically, ethers are moderately inert Thioester Formation – esterification of the carboxyl Do not normally react with reducing agents or bases group Extremely volatile Highly flammable = easily oxidized in air Symmetrical ethers may be prepared by dehydrating two alcohol molecules Requires heat and acid catalyst In Krebs cycle, the conversion of a-ketoglutarate to succinyl-CoA is an important step that yields energy. CARBOXYLIC ACID REACTIONS Neutralization - do react with strong bases to form carboxylate salts. REACTIONS OF THIOLS 14  Hunsdiecker Reaction (Decarboxylation) - use of silver salts of carboxylic acids in the presence of bromine or chlorine to synthesize alkyl halide. Glycolysis (Decarboxylation) - The decarboxylation mechanism replaces the carboxyl group in a carboxylic acid with hydrogen. The reaction is REACTIONS OF ALDEHYDES AND KETONES facilitated by a group of enzymes called Addition Reaction decarboxylases or carboxy-lyases. - Principal reaction is the addition reaction across the polar C=O double bond - Very similar to the addition hydrogenation of alkenes - Requires catalytic acid in the solution - Product of the reaction is a hemiacetal - Hemiacetals are quite reactive REACTIONS OF ESTERS - Undergo a substitution reaction with the –OH Esterification group of the hemiacetal is exchanged for - Carboxylic acids react with alcohols to form: another –OR group from the alcohol -Esters - Reaction product is an acetal -Water - This reaction is reversible -The reaction is catalyzed by strong acid -Heat is required -A condensation reaction Aldehyde Ketone HYDROLYSIS - a bond is broken by the addition of a water molecule. - Acid Hydrolysis - Base Hydrolysis (Saponification) Hemiacetals and Acetals in Carbohydrates Phosphoric acid reacts with alcohols to produce a phosphate ester or phosphoester The ester can then react with a second or third acid to give phosphoanhydride ADP and ATP of biochemistry fame are important examples of phosphate esters 15  IMPORTANT MONOSACCHARIDES II. MIDTERMS 1. Glucose - The most important aldohexose sugar in the CARBOHYDRATES human body (dextrose, grape sugar, and A. FUNCTIONS AND CLASSIFICATIONS OF blood sugar) CARBOHYDRATES - Normal blood glucose levels = 100 mg/100 mL blood Carbohydrates are represented as CHO (often called as - Controlled by insulin and glucagon sugars). Its general formula is Cn(H2O)n (for 2. Fructose monosaccharides). - A ketohexose and fruit sugar (levulose) - Found in honey, corn syrup, and sweet fruits - Generally defined as polyhydroxy aldehydes or 3. Galactose ketones - A diastereomer of glucose - Major source of energy for the body - Found in lactose or milk sugar - Oligosaccharides (key role in cell interactions and - Modified form is B-dacetylgalactosamine, a immune recognitions) component of blood group antigens - Polysaccharides (structural components of bacterial cell walls and some classes of organisms). CLASSIFICATION OF CARBOHYDRATES 1. MONOSACCHARIDE - A carbohydrate that cannot be hydrolyzed to a simpler carbohydrate - Building blocks of all carbohydrates - ALDOSE : A monosaccharide containing an aldehyde 4. Ribose and Deoxyribose group - Important aldopentoses which are - KETOSE : A monosaccharide containing a ketone components of RNA and DNA respectively. group FISCHER PROJECTIONS AND THE D, L NOTATION FISCHER PROJECTION: Bonds are written in a ➔ The most common monosaccharides in the nature are two-dimensional representation showing the the aldohexose D-glucose and the ketohexose configuration of tetrahedral stereocenters D-fructose - horizontal lines represent bonds projecting ➔ The aldopentoses Dribose and 2-deoxy-Dribose are forward components of nucleotides and nucleic acids. - vertical lines represent bonds projecting to the rear - the carbon atom at the intersection of the horizontal and vertical lines is not shown 16  STRUCTURES OF STRUCTURES OF D-ALDOSES D-KETOSES According to the conventions proposed by Fischer - D-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH on its penultimate carbon on the right - L-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH on its penultimate carbon on the left CYCLIC SUGARS (FORMATION OF A HEMIACETAL) Cyclization of sugars takes place due to interaction between functional groups of aldehyde and alcohol on Stereoisomers distant carbons, C1 to C5, to make a cyclic - same molecular formula and bonding pattern hemiacetal but different spatial arrangement. Cyclization using C2 to C5 of ketones and alcohol Enantiomers results in hemiketal formation. - stereoisomers that are mirror images In both cases, the carbonyl carbon is the new chiral - example: D-erythrose and L-erythrose are center and becomes an anomeric carbon enantiomers Diastereomers - stereoisomers that are not mirror images - example: D-erythrose and D-threose 17  HAWORTH PROJECTIONS Haworth Projections of Sugars five- and six-membered hemiacetals are represented - Recognizing cyclic sugars (a or b-sugar) as planar pentagons or hexagons, as the case may be, viewed through the edge most commonly written with the anomeric carbon on the right and the hemiacetal oxygen to the back right the designation − means that -OH on the anomeric carbon is cis to the terminal -CH2OH; − means that it is trans Converting Fischer Formula to Haworth Projections 2 Hemiacetal Forms of D-glucose - Alpha-form (a) -OH of C1 and CH2OH are on opposite sides - Beta-form (B) -OH of C1 and CH2OH are on same sides 1. Assign numbers for carbon atoms in the Fischer stereochemistry 2. For C2-C4, consider the –OH group on right side written downward and the -OH group on the left side written upward in the Haworth structure. 3. For C1(anomeric carbon), the –OH group is either “up” or “down” depending on which face of the COMPARISON OF FISCHER AND HAWORTH’S carbonyl is attacked PROJECTION For C1: the - anomer has –OH → down ( for D-sugars) the - anomer has –OH → up (for D-sugars) 4. For C5, if –OH is on the right side of the Fischer, it’s a D-sugar. This will place the C6 on the top of the Haworth projection. If–OH is on the left side, it’s an L-sugar so the C6 is written at the bottom of the structure Example: Convert D-mannose to a Haworth in the - pyranose configuration Convert D-galactose to a Haworth in the - pyranose configuration Convert D-sorbose to a Haworth in the - furanose configuration 18  ➔ A common table sugar extracted from sugarcane and sugar beets ➔ non reducing sugar (no free aldehyde or ketone in its structure) ➔ One unit of D-glucose and one unit of D-fructose joined by an a-1,2- glycosidic bond CLASSIFICATION OF CARBOHYDRATES 2. DISACCHARIDE a carbohydrate composed of 2 monosaccharide groups and can be broken down into simple sugars Hydrolysis (breaking down of disaccharide) Condensation (forming disaccharide) 2. LACTOSE Disaccharides can be broken into simple sugar units ➔ Milk sugar (breast milk -7% and cow’s milk – by the hydrolysis reaction: 4.7%) Disaccharide + water → 2 monosaccharides ➔ Made up of D-galactose and one unit of Examples: Dglucose joined by a b-1,4-glycosidic bond - Sucrose + water → glucose + fructose (reducing sugar) - Lactose + water → galactose + glucose - Maltose + water → glucose + glucose - Trehalose + water → glucose + manose Glycosidic Bond Formation Glycoside: a carbohydrate in which the -OH of the anomeric carbon is replaced by -OR those derived from furanoses are furanosides; those derived from pyranoses are pyranosides CLINICAL IMPLICATIONS Glycosidic Bond: the bond from the anomeric carbon 1. LACTOSE Intolerance to the -OR group 01. Defective or missing enzymes = lactase This is the basis for the formation of polysaccharides 02. Normally, intestinal villi degrades lactose to and oligosaccharides be absorbed by the bloodstream 03. Lactase produced by intestinal bacteria forms H2 , CO2, and organic acids which may cause diarrhea, bloating, abdominal pain, flatulence and colic 2. GALACTOSEMIA A metabolic disorder common among newborn babies High levels of galactose in blood cells Two Different Disaccharides of D-Glucose Caused by mutation of the GALT gene for type 1 galactosemia Glycosidic linkages can take various forms; the Aldose reductase converts galactose to galactitol – a anomeric carbon of one sugar to any of the -OH toxic substance groups of another sugar to form an a - or B-glycosidic linkage. Children receiving treatment may continue to have the following: ❖ Speech delays. ❖ Learning disabilities. ❖ Behavioral problems. ❖ Balance and coordination problems (ataxia). ❖ Tremors. IMPORTANT DISACCHARIDES 2. MALTOSE ➔ Two units of D-glucose joined by an a-1,4-glycosidic 1. SUCROSE bond 19  ➔ Formed from the hydrolysis of starch - Ex. Oxidation using Tollen’s reagent (aldonic ➔ Differs from cellobiose by the conformation of the acid) glycosidic linkage 3. CELLOBIOSE ➔ hydrolyzed from cellulose ➔ white crystalline watersoluble disaccharide. It is made up of two molecules of glucose joined by B -(1- 4)-glycosidic bond ➔ can be digested by ruminants ➔ REDUCTION: The carbonyl group in a monosaccharide (either an aldose or a ketose) is reduced to a hydroxyl group using hydrogen as the reducing agent (alditols) CLASSIFICATION OF CARBOHYDRATES - Ex. Sorbitol - used as moisturizing agents in foods and cosmetics and as a sweetening 3. OLIGOSACCHARIDES agent in chewing gum a carbohydrate composed of 3 or more monosaccharide groups and can be broken down into simple sugars - EX. RAFFINOSE: found in sugar beet, cotton seed, and many grains - Raffinose + water → glucose + fructose + galactose ➔ PHOSPHATE ESTER FORMATION: The hydroxyl groups of a monosaccharide can react with inorganic oxyacids to form inorganic esters - Phosphate esters of various monosaccharides are stable in aqueous solution and play important roles in the metabolism of carbohydrates E. REACTION OF MONOSACCHARIDES ➔ Oxidation: : strong oxidizing agents can oxidize both ends of a monosaccharide at the same time (the carbonyl group and the terminal primary alcohol group) to produce a dicarboxylic acid - such polyhydroxy dicarboxylic acids are known as aldaric acids. 20  CLASSIFICATION OF CARBOHYDRATES 4. POLYSACCHARIDE a carbohydrate composed of 7 or more units of monosaccharide. Important in structural supports, particularly in plants, protection, and serves as a storage depot for monosaccharides Homopolysaccharides – 1 type of monomer Heteropolysaccharides – 2 or more types of IODINE-STARCH COMPLEX monomer STRUCTURE AND FUNCTIONS OF POLYSACCHARIDES CELLULOSE The major structural component of plants, especially wood and plant fibers a linear polymer of approximately 2800 D-glucose units per molecule joined by b-1,4-glycosidic bonds extensive intra- and intermolecular hydrogen bonding between chains GLYCOGEN Humans lack cellulase to hydrolyze cellulose Human and animal storage polysaccharide It serves as dietary fiber (20-35 g daily as recommended by NIH) Branched chain polymer (contains only glucose units ) – alpha (1→4) glycosidic bonds in straight chains and alpha (1→6) in branches Molecular Mass: 3,000,000 (up to 1,000,000 glucose STARCH units) Three times more highly branched than is used for energy storage in plants amylopectin in starch a polymers of -D-glucose units Excess glucose in blood stored in the form of amylose: continuous, unbranched chains of up to glycogen 4000 -D-glucose units joined by -1,4-glycosidic bonds amylopectin: a highly branched polymer consisting of 24-30 units of Dglucose joined by -1,4-glycosidic bonds and branches created by -1,6- glycosidic bonds - amylases catalyze hydrolysis of -1,4-glycosidic bonds - B-amylase is an exoglycosidase and cleaves from the nonreducing end of the polymer - B-amylase is an endoglycosidase and hydrolyzes glycosidic linkages anywhere along the chain to produce glucose and maltose - debranching enzymes catalyze the hydrolysis of -1,6-glycosidic bond 21  ❖ Heparin/Heparan Sulfate: - Repeating units of disaccharide of sulfonated uronic acid and glucosamine - Found on the surface of endothelial and surrounding tissues in large quantities. - regulate numerous functions in the blood vessel wall, including blood coagulation, inflammation response, and cell differentiation. ❖ Hyaluronic acid: - composed of repeating units of D-glucuronic acid and N-acetylglucosamine - trap water inside tissue cells, keeping the CHITIN skin and eyes moist and the joints lubricated the major structural component of the exoskeletons of (humectant) invertebrates, such as insects and crustaceans; also - a component of the vitreous humor of the occurs in cell walls of algae, fungi, and yeasts eye and the lubricating fluid of joints PEPTIDOGLYCAN: - Activation of inflammatory cells the major structural component of bacterial cell walls. ❖ Chondroitin sulfate and keratan sulfate: A linear heteropolysaccharide consisting of two - components of connective tissue chains of alternating amino sugars, namely - CS - building blocks of cartilage N-acetylglucosamine and N-acetylmuramic acid - large quantities as OTC drugs used to help connected by a β-(1,4)-glycosidic bond. repair frayed or damaged cartilage, especially in knees ACIDIC POLYSACCHARIDES - KS - found in cartilage, cornea, and brain. It plays a role in maintaining the regular GLYCOSAMINOGLYCANS (GAGs) spacing of collagen fibrils in the eye, allowing are linear acidic heteropolysaccharides containing light to pass through. repeating disaccharide units with an amino sugar and a sugar with a negative charge due to a sulfate or a G. Glycoproteins: CELL RECOGNITION carboxyl group Glycoproteins: contain carbohydrate units covalently bonded Structural polysaccharides present in connective to a polypeptide chain tissues associated with joints, cartilage, and synovial - antibodies are glycoproteins fluids in animals and humans - Oligosaccharide portion of glycoproteins act as Primary function is lubrication necessary for joint antigenic determinants movement - Among the first antigenic determinants discovered Structure and Functions of Acidic Polysaccharides were the blood group substances Extracellular Matrix – intercellular space between cells of - In the ABO system, individuals are classified either epithelial or endothelial origin according to four blood types: A, B, AB, and O Composed of two major classes of biomolecules - GAGs are covalently linked to protein forming proteoglycans - Fibrous proteins (collagen, elastin, and fibronectin) Important Polysaccharides GAGs are classified according to structure and families: 22  FUNCTIONS OF LIPIDS TYPES OF LIPIDS Fatty Acids - Saturated LIPIDS - Unsaturated Glycerides LIPIDS - glycerol-containing lipids - a heterogeneous class of naturally occurring Nonglyceride lipids organic compounds with varying chemical - Sphingolipids composition and classified together based - Steroids on their solubility with nonpolar solvents - Waxes - insoluble in water due to the long chains of Complex lipids (lipoprotein) hydrocarbon (C-H) bonds - Amphipathic in nature STRUCTURE OF LIPIDS Interactions of biochemical compounds with water - When placed in water, simple lipids form structures Lipids exhibit structural diversity like micelles, arranging themselves spherically in an Some are esters, some are amides, and some are aqueous solution. alcohols (acyclic and cyclic) and some are polycyclic. 23  FATTY ACIDS STRUCTURE OF FATTY ACIDS an unbranched-chain carboxylic acid, most commonly of 12 - 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or phosphodiacylglycerols of biological membranes Even # of Carbon atoms: (a) Long-chain fatty acids: C12 - C26 (b) Medium-chain fatty acids: C6 - C11 (c) Short-chain fatty acids: C4 - C5 TWO TYPES OF FATTY ACIDS 1.. Saturated - all C-C bonds are single bonds 2. Unsaturated – (a) monounsaturated: one C=C bond (b) polyunsaturated: 2 or more C=C bonds present - up to six double bonds are present in fatty acids EXAMPLES OF FATTY ACIDS Omega Fatty Acids Nutritionally important Omega-3 and Omega-6 fatty acids - Linolenic acid – Omega-3 a. saturated b. monounsaturated c. polyunsaturated - Linoleic acid – Omega-6 Linoleic Acid Deficiency: - Skin redness - becomes irritated - Infections and dehydration - Liver abnormalities - Children need it the most ESSENTIAL FATTY ACIDS Alpha Linolenic Acid (ALA) - found in plants (flaxseed, walnuts, canola and soybean DHA and EPA - Marine sources - Produced by microalgae(anchovi es, mackerel, salmon, and sardines) Linoleic Acid EXAMPLES OF COMMON FATTY ACIDS - found in safflower, corn and soybean oils The common fatty acids found in biological systems are shown in Table 8.1 Arachidonic Acid - fish, meat and eggs - Precusor of eicosanoids 24  PROPERTIES OF FATTY ACIDS Water solubility: Shortchain fatty acids are sparingly Lipid esters of glycerol and fatty acids soluble whereas long-chain fatty acids are insoluble (monoglycerides, diglycerides, and triglycerides) Melting Point; depends upon: TWO CLASSES: - length of the carbon chain - neutral glycerides (nonionic and nonpolar) - degree of unsaturation (number of double - Phosphoglycerides (ampiphatic) bonds in a molecule) ‘ TRIGLYCERIDES (TRIACYLGYLYCEROLS) Space-Filling Molecules Esters of 1 molecule of glycerol with three fatty acids - the number of bends in a fatty acid chain (TAGs) increases as the number of double bonds called neutral fats and serve as energy storage in the increases fat cells of adipose tissue. - Less packing occurs - The melting point is lower - Tend to be liquids at room temperature FATS (SOLID) OILS (LIQUID) derived from derived from plants animals (beef, pork, and marine animals & chicken) (essential oils and mixture of high fish oil) Mixture of percentage of long a high degree of CLASSIFICATION OF LIPIDS chains saturated unsaturated fatty FA and less degree acids and less of of unsaturation saturated FA BIOLOGICAL WAXES A mixture of esters of long-chain carboxylic acids and alcohols Reactions of Fatty Acids and Glycerides Found as protective coatings for plants and animals Commonly used in pharmaceuticals and cosmetics 1. ESTERIFICATION GLYCERIDES 25  - Fatty acids react with long chain alcohols to produce water and esters (biological waxes) 4. SAPONIFICATION (BASE HYDROLYSIS) natural soaps (fatty acid salts) are prepared by boiling triglycerides (animal fats or vegetable oils) with NaOH - 3 molecules of fatty acids react with glycerol to or KOH in a reaction produce water and triglyceride 2. HYDROGENATION an addition reaction when unsaturated fatty acids are converted to saturated fatty acids commonly used in the food industry PHOSPOLIPIDS Phosphate ester lipids derived from phosphoric acid polar head (the phosphoryl group) and a nonpolar tail (the alkyl chain of the fatty acid) Phospholipids dominate up to 80% of the mass of a cell membrane. - TYPES: ❖ Phosphoglycerides (Phosphoacylglycerides) ❖ Sphingolipids (Sphingomyelin) 3. ACID HYDROLYSIS Waxes or triglycerides may be hydrolyzed in the presence of acid or biological enzymes to form alcohol and fatty acids Unlike the soaps, these molecules are highly amphipathic, and when mixed with water spontaneously form membranes that are described as lipid bilayers. 26  agents (emulsifying agent) Phosphatidylethanolamine - known as Cephalins - Found in brain tissue and nerves - Responsible for blood coagulation Phosphatidylserine - isolated from brain lipids and PHOSPHOGLYCERIDES considered as Cephalins Also known as Phosphoacylglycerols or - Found in brain Glycerophospholipid tissue and nerves Glycerol is esterified to phosphoric acid - involved in signal Phosphatidic acid is esterified to 2 fatty acids transduction activity -OH group from Phosphatidic acid is esterified to an amino alcohols (R group) Most abundant type of phospholipids in the cell Phosphatidylinositol membrane - minor component of cell membrane Phosphatidate is the simplest - Phosphatidylinosito l 4,5- bisphosphates (PIP2), serve as signaling molecules in chemical communication ➔ The classification of phosphatidyl ester depends on Sphingolipids the nature of the second alcohol esterified to phosphoric acid 1. Sphingomyelins - major component of myelin sheaths in nerve cells - Sphingosine (amino alcohol)serve as the head structure - Ceramides are the simplest compound in this class Ceramides PHOSPHOGLYCERIDES - create a skin barrier that helps prevent moisture loss Phosphatidylcholine - known as Lecithin - major constituent of cell membrane and pulmonary surfactant - micelle-forming 27  2. Glycolipids (Glycosphingolipids) - synthesized in the - synthesized in the - built on carbohydrate and ceramide testes ovaries (Cerebrosides) - responsible for the - responsible for the - Cerebrosides contain at least one development of development of monosaccharide (glucose or galactose) male secondary female secondary - Glucocerebrosides are found in sex characteristics sex characteristics macrophages (ingest and destroy foreign - Testosterone and control of the microorganisms) menstrual cycle SPHINGOLIPIDS Galactocerebrosides are ADRENOCORTICOID HORMONES found almost exclusively in - produced by adrenal glands the membranes of the brain - Mineralocorticoids: control the balance of Na and K cells ions in cells - Glucocorticoid: control glucose metabolism and Gangliosides contain an counteract inflammation oligosaccharide group (3 monosaccharides) ➔ These oligosaccharide groups always contain one or more molecules of Nacetylneuraminic acid (sialic acid) EICOSANOIDS STEROIDS EICOSANOIDS ➔ arachidonic acid (20:4) derivatives ❖ a group of lipids that have fusedring structure of 3 ➔ Have profound physiological effects at extremely low six-membered rings, and 1 five-membered ring concentrations ❖ derivatives of cholesterol ➔ Short-lived hormone-like molecules ➔ Names are based on ring substituents and number of 2 major classes of steroid hormones sidechain double bonds 1. Sex hormones - control reproduction and secondary sex characteristics 2. Adrenocorticoid hormones – control numerous biochemical processes in the body for metabolism STEROID SEX HORMONES ANDROGEN: MALE SEX ESTROGENS: FEMALE HORMONES SEX HORMONES 28 THROMBOXANES - Inhibition of hormone-sensitive lipases ➔ cyclic ether ring and oxygencontaining functional groups 5. Kidneys ➔ promote platelet aggregation - Prostaglandins dilate renal blood vessels - Results in increased water and electrolyte