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Instructor: Dr. Khairul I AnsariOffice: 316CPB

Phone: 817-272-0616email: kansari@uta.eduOffice hours 12 am – 1:30 pm Tuesday &.Thursday

CHEM 4311

General Biochemistry I

Fall 2012

Chapters 1, 2 and 7

General Biochemistry I

“Living things are composed of molecules”

Understand the basics of biological system, biomolecules and their chemistry

Goal

What is life? How life functions?

Chemistry of life?

“Post genomic era” –Special stage of Biochemistry

“Post genomic era” –Special Stage of Biochemistry

●Nearly complete sequence of the human genome has been determined

● Complete human genome is 3 X 109bp

● It’s a blueprint for “ what it means to be human”

● Scientist can begun identification and characterization

of gene sequences

● Still we need to know a lots of information to understand completely

Distinctive Properties of Living Systems

• Living systems have a remarkable capacity for self-replication

• 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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Organelles

Macromolecules

Metabolites

Building blocks

CO2, H2O, NH3 etc

Amino acids and Proteins

Nucleic acids

Carbohydrates

Lipids

Biomolecules

You need to study Chapter 1 & 2

Chapter 1

Chemistry Is the Logicof 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 viral-

specific 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?

Ionization of water

Acid-base Equilibria

The pH Scale

• A convenient means of writing small concentrations:

• pH = -log10 [H+]

• Sørensen (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 - ] ____________________

[HA]

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]

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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.

Consider the Dissociation of

Acetic AcidAssume 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.

Amino acids and Proteins

Nucleic acids

Carbohydrates

Lipids

BiomoleculesCarbohydrates

Carbohydrates in food are important source of energy

Human consumes ~200 grams of glucose/day

Starch, found in food such as rice, pasta, consist of chains of linked glucose molecules.

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

building blocks for other molecules

Carbohydrates and the Glycoconjugates

of Cell Surfaces

● Versatile class of moleculesformula (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

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

Transformation others

• 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?

• 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

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

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

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

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.

Family Tree of D-Aldoses

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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.

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 plane-polarized light!

• All structures in Figures 7.2 and 7.3 are D

• D-sugars predominate in nature

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

More Stereochemistry

Know these definitionsStereoisomers 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 diastereomersAny 2 sugars in a row in 10.2 and 10.3 are diastereomers

Two sugars that differ in configuration at only

one chiral center are epimers

Cyclic monsaccharide structures and anomeric forms

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

• Fructose (a ketose) can cyclize to form a cyclic hemiketal

R-OH

Acetal

Alcohols reacts with carbnyl to form acetal

and ketals

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The linear form of D-glucose undergoes an

intramolecular reaction to form a cyclic hemiacetal.

R-OH

Acetal

The linear form of D-glucose undergoes an

intramolecular reaction to form a cyclic hemiacetal.

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

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

Ring structures: Pyranoses and Furanose

Anomeric carbon: Ketone or aldehyde carbon that becomes chiral upon

ring formationAnomers: 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

Specific optical

rotation: 112.2º

Specific optical

rotation: 18.7º

Q. What is the composition of a mixture α-D-Glucose and β-D-Glucose

which has specific rotation of 83.0 º?

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

[α]D20 =

rotation (degrees)

path length (dm) × conc (g/mL)

What kinds of chemistry monosaccharides

can have?

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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.

CH3OH

CH3OH

Acetals, ketals and glycosides:

basis for oligo- and poly-saccharides

Structure and Chemistry of Oligosaccharides

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

It’s 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

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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 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

O-beta-D galaactopyranosyl-1-4-D-gluopyranose

Maltose (Glucose……??????? …………Glucose

Homodisaccharide, used in beverages

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

Figure 7.18 The structures of several important disaccharides. Note that the notation -

HOH means that the configuration can be either α or β. If the -OH group is above the

ring, the configuration is termed β. The configuration is α 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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Figure 7.20 Some antibiotics are oligosaccharides or contain oligosaccharide groups.

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

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 α(1 → 4), but the branches in amylopectin are α(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)

Figure 7.24 Dextran is a branched polymer of D-glucose units. The main

chain linkage is α(1→6), but 1→2,

1 →3, or 1→4 branches can occur.

Dextrans

A small but significant difference from starch and glycogen

• 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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Figure 7.25 Sephadex gels are formed from dextran chains cross-linked 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.

Structural Polysaccharides

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

Figure 7.26 (a) Amylose, composed exclusively of the relatively bent α(1→4) linkages, prefers to adopt a helical conformation, whereas (b) cellulose, with β(1→4)-glycosidic linkages, can adopt a fully extended conformation with alternating 180°flips 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.

Structural Polysaccharides

Composition similar to storage polysaccharides,

but small structural differences greatly

influence properties

• Beta(1,4) linkages make all the difference!

• Strands of cellulose form extended ribbons