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General Biochemistry I

CHEM 4311 General Biochemistry I Fall 2012

Chapters 1, 2 and 7

Instructor: Office: Phone: email: Office hours

Dr. Khairul I Ansari 316CPB 817-272-0616 kansari@uta.edu 12 am 1:30 pm Tuesday &.Thursday

Goal
What is life? Chemistry of life? How life functions?

Post genomic era Special Stage of Biochemistry

Nearly complete sequence of the human genome has been determined
Complete

human genome is 3 X 109bp

Post genomic era Special stage of Biochemistry Living things are composed of molecules

Its

a blueprint for what it means to be human

Scientist

can begun identification and characterization of gene sequences

Understand the basics of biological system, biomolecules and their chemistry

Still

we need to know a lots of information to understand completely

Distinctive Properties of Living Systems

Living systems have a remarkable capacity for selfreplication Living systems are actively engaged in energy transformations Organisms are complicated and highly organized Biological structures serve functional purposes Each cell of a given organism carry same genetic information

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CO2, H2O, NH3 etc Metabolites Building blocks Macromolecules Nucleic acids

Biomolecules
Amino acids and Proteins

Organelles Carbohydrates

Lipids

Chapter 1
You need to study Chapter 1 & 2
Chemistry Is the Logic of Biological Phenomena
Biochemistry by Reginald Garrett and Charles Grisham

Outline
What Are the Distinctive Properties of Living Systems? What Kinds of Molecules Are Biomolecules? What Is the Structural Organization of Complex Biomolecules? How Do the Properties of Biomolecules Reflect Their Fitness to the Living Condition? What Is the Organization and Structure of Cells? What Are Viruses?

Figure 1.25 The virus life cycle. Viruses are mobile bits of genetic information encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viralspecific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease.

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Chapter 2
Water: The Medium of Life
Biochemistry by Reginald Garrett and Charles Grisham

Outline
What Are the Properties of Water? What is pH? What is pKa? Henderson equation? What Are Buffers, and What Do They Do? Does Water Have a Unique Role in the Fitness of the Environment?

Acid-base Equilibria
The pH Scale Ionization of water A convenient means of writing small concentrations: pH = -log10 [H+] Srensen (Denmark) If [H+] = 1 x 10 -7 M Then pH = 7

Dissociation of Weak Electrolytes

Consider a weak acid, HA The acid dissociation constant is given by: HA H+ + A Ka = [ H + ] [ A - ]
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The Henderson-Hasselbalch Equation

Know this! You'll use it constantly. For any acid HA, the relationship between the pKa, the concentrations existing at equilibrium and the solution pH is given by: pH = pKa + log10
[A ] [HA]

[HA]

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Consider the Dissociation of Acetic Acid

Figure 2.11 The titration curve for acetic acid. Note that the titration curve is relatively flat at pH values near the pKa. In other words, the pH changes relatively little as OH- is added in this region of the titration curve.

Assume 0.1 eq base has been added to a fully protonated solution of acetic acid The Henderson-Hasselbalch equation can be used to calculate the pH of the solution: With 0.1 eq OH added: pH = pKa + log10 [0.1] [0.9] pH = 4.76 + (-0.95) pH = 3.81

Consider the Dissociation of Acetic Acid

Another case.... What happens if exactly 0.5 eq of base is added to a solution of the fully protonated acetic acid? With 0.5 eq OH added: pH = pKa + log10 [0.5] [0.5] pH = 4.76 + 0 pH = 4.76 = pKa

Consider the Dissociation of Acetic Acid

A final case to consider.... What is the pH if 0.9 eq of base is added to a solution of the fully protonated acid? With 0.9 eq OH added: pH = pKa + log10 [0.9] [0.1] pH = 4.76 + 0.95 pH = 5.71

Figure 2.12 The titration curves of several weak electrolytes: acetic acid, imidazole, and ammonium. Note that the shape of these different curves is identical. Only their position along the pH scale is displaced, in accordance with their respective affinities for H+ ions, as reflected in their differing pKa values.

Figure 2.13 The titration curve for phosphoric acid. The chemical formulas show the prevailing ionic species present at various pH values. Phosphoric acid (H3PO4) has three titratable hydrogens and therefore three midpoints are seen: at pH 2.15 (pK1), pH 7.20 (pK2), and pH 12.4 (pK3).

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What Are Buffers, and What Do They Do?

Buffers are solutions that resist changes in pH as acid and base are added Most buffers consist of a weak acid and its conjugate base Note in Figure 2.14 how the plot of pH versus base added is flat near the pKa Buffers can only be used reliably within a pH unit of their pKa

Figure 2.14 A buffer system consists of a weak acid, HA, and its conjugate base, A-. The pH varies only slightly in the region of the titration curve where [HA] = [A-]. The unshaded box denotes this area of greatest buffering capacity. Buffer action: when HA and A- are both available in sufficient concentration, the solution can absorb input of either H+ or OH-, and pH is maintained essentially constant.

Biomolecules
Amino acids and Proteins

Carbohydrates
Carbohydrates in food are important source of energy

Nucleic acids

Human consumes ~200 grams of glucose/day Starch, found in food such as rice, pasta, consist of chains of linked glucose molecules.

Carbohydrates

These chains are broken down into individual glucose molecules for eventual use in generation of ATP and building blocks for other molecules

Lipids

Carbohydrates and the Glycoconjugates of Cell Surfaces

Versatile class of molecules formula (CH2O)n, Hydrates of Carbon Aldehydes and Ketone compounds with multiple hydroxyl groups Serves as energy store in all organism Metabolic precursors of virtually all other biomolecules

What is the structure, chemistry, and biological function of carbohydrates?

Nomenclature of carbohydrates Structure and Chemistry of Monosaccharides? Structure and Chemistry of Oligosaccharides? Structure and Chemistry of Polysaccharides?

Linked with proteins and lipids (Glycoconjugates) Recognition, cell growth Transformation others

Glycoproteins and Their Function in Cells? Proteoglycans Modulate Processes in Cells and Organisms?

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How Are Carbohydrates Named?

Carbohydrates are hydrates of carbon (C.H2O)n Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions Oligosaccharides = "a few" - usually 2 to 10 Polysaccharides are polymers of the simple sugars

Structure and Chemistry of Monsaccharides?

Aldehydes and ketones with two or more hydroxyl group, emperical formula (CH2O)n Conatins typically 3-7 carbon atoms Smallest monosacharides (n=3, trioses) are D and L Glyceraldehyde and dihydroxyacetone Review Fisher Projection, D and L configurations

Review of Stereochemistry of Monosaccharides

Stereochemistry is a prominent feature of monosaccharides Aldoses with at least 3 carbon atoms----have chiral centers Ketoses with at least 4 carbon atoms contain chiral centers

Nomenclature of the molecule must specify the configuration of each asymmetric center Fischer projection formula is used almost universally for this purpose

Structure of a simple aldose (glyceraldehyde) and a simple ketose (dihydroxyacetone).

D and L refers to the configuration of the highest numbered asymmetric carbon atom D : OH group is on the right L OH group on the left

Family Tree of D-Aldoses

D and L relates to the configuration with glyceraldehyde BUT DOES NOT specify the sign of rotation of the plate polarized light If rotation needs to be specified them mention (+ and -) alongwith D/L D(+) Glucose---Dextro D(-) Fructose----Leavo
The configuration in each case is determined by the highest numbered asymmetric carbon (shown in gray). In each row, the new asymmetric carbon is shown in yellow.

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Stereochemistry Review
Read text on p. 204-207 carefully! D,L designation refers to the configuration of the highest-numbered asymmetric center D,L only refers the stereocenter of interest back to D- and L-glyceraldehyde! D,L do not specify the sign of rotation of planepolarized light! All structures in Figures 7.2 and 7.3 are D D-sugars predominate in nature

The structure and stereochemical relationships of D-ketoses having three to six carbons. The configuration in each case is determined by the highest numbered asymmetric carbon (shown in gray). In each row, the new asymmetric carbon is shown in yellow.

More Stereochemistry
Know these definitions Stereoisomers that are mirror images of each other are enantiomers Pairs of isomers that have opposite configurations at one or more chiral centers but are NOT mirror images are diastereomers Any 2 sugars in a row in 10.2 and 10.3 are diastereomers

D-Fructose and L-fructose, an enantiomeric pair. Note that changing the configuration only at C5 would change D-fructose to L-sorbose.

Two sugars that differ in configuration at only one chiral center are epimers

Cyclic monsaccharide structures and anomeric forms

Alcohols reacts with carbnyl to form acetal and ketals

R-OH Acetal

Glucose (an aldose) can cyclize to form a cyclic hemiacetal Fructose (a ketose) can cyclize to form a cyclic hemiketal

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The linear form of D-glucose undergoes an intramolecular reaction to form a cyclic hemiacetal.

The linear form of D-glucose undergoes an intramolecular reaction to form a cyclic hemiacetal.

R-OH Acetal

The linear form of D-fructose undergoes an intramolecular reaction to form a cyclic hemiketal.

Cyclic monosaccharide structures possess anomeric forms

For D-sugars, alpha has OH down, beta up For L-sugars, the reverse is true

D-Glucose can cyclize in two ways, forming either furanose or pyranose structures.

D-Ribose and other five-carbon saccharides can form either furanose or pyranose structures.

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Carbohydrates (CH2O)n, n 3 Nomenclature: Monosaccharides, Olio- and polysaccharides Classification (Family Trees) Aldose (aldehyde) and ketose (ketone) Triose, tetrose, pentose, hexose, etc. Stereochemistry D- and L- Configuration: Epimers: Two molecules that differ in configuration about 1 asymmetric carbon

Figure 7.9 (a) Chair and boat conformations of a pyranose sugar. (b) Two possible chair conformations of -D-glucose.

Ring structures: Pyranoses and Furanose Anomeric carbon: Ketone or aldehyde carbon that becomes chiral upon ring formation Anomers: a, b differ in configuration about anomeric carbon a-Configuration: In Fischer projection, OH of anomeric carbon on same side as OH of highest numbered asymmetric carbon b-Configuration: In Fischer projection, OH of anomeric carbon on opposite side as OH of highest numbered asymmetric carbon Haworth projections: Three-dimensional representation: Groups to right in Fischer projection draw down in Haworth projection Conformations Chair and boat conformations due to ring pucker Axial and equatorial orientation of groups attached to ring

Cyclic monosaccharide structures possess anomeric forms

For D-sugars, alpha has OH down, beta up For L-sugars, the reverse is true

Mutarotation

What kinds of chemistry monosaccharides can have?

Specific optical rotation: 112.2

Specific optical rotation: 18.7

The specific rotation is the number of degrees through which plane polarized light is rotated in traveling 1-decimeter through a sample of 1g/mL

[] 20 = D

rotation (degrees) path length (dm) conc (g/mL)

Q. What is the composition of a mixture -D-Glucose and -D-Glucose which has specific rotation of 83.0 ?

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Monosaccharide Derivatives
Reducing sugars: sugars with free anomeric carbons they will reduce oxidizing agents, such as peroxide, ferricyanide and some metals (Cu and Ag)

These redox reactions convert the sugar to a sugar acid Glucose is a reducing sugar - so these reactions are the basis for diagnostic tests for blood sugar

Figure 7.10

Sugar alcohols: mild reduction of sugars

Deoxy sugars: constituents of DNA, etc.

OH

OH

D-Ribose

Several sugar esters important in metabolism.

Figure 7.14 Structures of D-glucosamine and D-galactosamine.

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Figure 7.15 Structures of muramic acid and neuraminic acid and several depictions of sialic acid.

Acetals and ketals can be formed from hemiacetals and hemiketals, respectively.

Acetals, ketals and glycosides: basis for oligo- and poly-saccharides

CH3OH

Structure and Chemistry of Oligosaccharides

CH3OH

Carbohydrates are hydrates of carbon (C.H2O)n

Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions

Its not important to memorize structures, but you should know the important features Be able to identify anomeric carbons and reducing and nonreducing ends Note carefully the nomenclature of links! Be able to recognize alpha(1,4), beta(1,4), etc

Oligosaccharides = "a few" - usually 2 to 10

Polysaccharides are polymers of the simple sugars

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Disaccharides are the simplest oligosaccharide Consist of two mono-saccharides

Sucrose, Maltose and lactose are the most

common in nature Reducing/Non reducing
O-beta-D galaactopyranosyl-1-4-D-gluopyranose Lactose is the principal carbohydrate in the milk, Can not be absorbed by the blood stream, needs lactase to hydrolyze it. Lactase is present in the intestine of nursing mammals Most people produce some amount of lactase

Maltose (Glucose???????

Glucose

Sucrose (Table Sugar): {Glucose-..???-Fructose)

Homodisaccharide, used in beverages

Figure 7.18 The structures of several important disaccharides. Note that the notation HOH means that the configuration can be either or . If the -OH group is above the ring, the configuration is termed . The configuration is if the -OH group is below the ring as shown. Also note that sucrose has no free anomeric carbon atoms. Figure 7.19 The structures of some interesting oligosaccharides.

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What is the Structure and Chemistry of Polysaccharides?

Functions: storage, structure, recognition Nomenclature: homopolysaccharide vs. heteropolysaccharide Starch and glycogen are storage molecules Chitin and cellulose are structural molecules Cell surface polysaccharides are recognition molecules
Figure 7.20 Some antibiotics are oligosaccharides or contain oligosaccharide groups.

Starch
A plant storage polysaccharide Two forms: amylose and amylopectin Most starch is 10-30% amylose and 70-90% amylopectin Branches in amylopectin every 12-30 residues Amylose has alpha(1,4) links, one reducing end

Figure 7.21 Amylose and amylopectin are the two forms of starch. Note that the linear linkages are (1 4), but the branches in amylopectin are (1 6). Branches in polysaccharides can involve any of the hydroxyl groups on the monosaccharide components. Amylopectin is a highly branched structure, with branches occurring every 12 to 30 residues.

Starch
A plant storage polysaccharide Amylose is poorly soluble in water, but forms micellar suspensions In these suspensions, amylose is helical iodine fits into the helices to produce a blue color
Figure 7.22 Suspensions of amylose in water adopt a helical conformation. Iodine (I2) can insert into the middle of the amylose helix to give a blue color that is characteristic and diagnostic for starch.

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Why branching in Starch?

Consider the phosphorylase reaction... Phosphorylase releases glucose-1-P products from the amylose or amylopectin chains The more branches, the more sites for phosphorylase attack Branches provide a mechanism for quickly releasing (or storing) glucose units for (or from) metabolism

Figure 7.23The starch phosphorylase reaction cleaves glucose residues from amylose, producing a-D-glucose-L-phosphate.

Glycogen
The glucose storage device in animals Hydrolysis of results glucose and maltose Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass Glycogen is stored energy for the organism Only difference from starch: number of branches Alpha(1,6) branches every 8-12 residues Like amylopectin, glycogen gives a red-violet color with iodine

Dextrans
A small but significant difference from starch and glycogen If you change the main linkages between glucose from alpha(1,4) to alpha(1,6), you get a new family of polysaccharides - dextrans Branches can be (1,2), (1,3), or (1,4)

Dextrans
A small but significant difference from starch and glycogen
Figure 7.24 Dextran is a branched polymer of D-glucose units. The main chain linkage is (16), but 12, 1 3, or 14 branches can occur.

Dextrans formed by bacteria are components of dental plaque Cross-linked dextrans are used as "Sephadex" gels in column chromatography These gels are up to 98% water!

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Structural Polysaccharides
Figure 7.25 Sephadex gels are formed from dextran chains crosslinked with epichlorohydrin. The degree of cross-linking determines the chromatographic properties of Sephadex gels. Sephacryl gels are formed by cross-linking of dextran polymers with N,N-methylene bisacrylamide.

Composition similar to storage polysaccharides, but small structural differences greatly influence properties Cellulose is the most abundant natural polymer on earth Cellulose is the principal strength and support of trees and plants Cellulose can also be soft and fuzzy - in cotton

Structural Polysaccharides
Composition similar to storage polysaccharides, but small structural differences greatly influence properties
Figure 7.26 (a) Amylose, composed exclusively of the relatively bent (14) linkages, prefers to adopt a helical conformation, whereas (b) cellulose, with (14)-glycosidic linkages, can adopt a fully extended conformation with alternating 180flips of the glucose units. The hydrogen bonding inherent in such extended structures is responsible for the great strength of tree trunks and other cellulose-based materials.

Beta(1,4) linkages make all the difference! Strands of cellulose form extended ribbons

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