9/7/2012
1
Instructor: Dr. Khairul I AnsariOffice: 316CPB
Phone: 817-272-0616email: [email protected] 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
9/7/2012
2
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.
9/7/2012
3
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]
9/7/2012
4
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).
9/7/2012
5
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?
9/7/2012
6
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
9/7/2012
7
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
9/7/2012
8
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.
9/7/2012
9
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?
9/7/2012
10
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.
9/7/2012
11
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
9/7/2012
12
•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.
9/7/2012
13
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.
9/7/2012
14
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!
9/7/2012
15
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