Macromolecules

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Macromolecules Biological macromolecules
including proteins, Sugars and nucleic acids are
the structural and functional bases of the cell.
Biological macromolecules are the polymerized
form of smaller organic molecules such as amino
acids, glucose, and nucleotides. These small
molecules are called monomers.
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Cells contain three different kinds of
macromolecules Proteins, polysaccharides and
nucleic acids. All three types are now
considered as informational molecules. DNA
sequence is genetically determined, which
directs the synthesis of proteins Proteins
including hormones and enzymes determines
metabolism of an organism Some polysaccharides
determines the half life of some proteins.
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Organization levels of a cell.
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I. Protein Structure and Function Amino acids
are building blocks (monomers) of proteins.
All amino acids consist of a center C, an amino
group (-NH3), an H atom, and a side chain, R.
COO- H3N - C - H
R
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R group is what makes an a.a. different from
each other.
 Amino acids in proteins are all L-amino acids.
 
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Classification of amino acids

• Depending on the type of side chain.
• Group I. non-polar side chains.
• Group II. polar, uncharged side chains
• Group III. acidic side chains
• Group IV. basic side chains

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Group I. Non-polar side chains
H3C H \ HC-C-COO- /
H3C NH3
H CH3-C-COO-
NH3
valine
alanine
H3C H \
HC-CH2-C-COO- / H3C
NH3
H3C H
H3C-CH2-CH-C-COO-
NH3
leucine
isoleucine
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Group I. Non-polar side chains
phenylalanine
proline
H2C CH-COO- H2C
NH2 H2C
H
CH3 -S-CH2-CH2-C-COO-

NH3
methionine
tryptophan
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Group II. Polar side chains
H
HO-CH2-C-COO-
NH3
H H-C-COO-
NH3
serine
glycine
HO H CH3-CH-C-COO-
NH3
tyrosine
threonine
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Group II. Polar side chains
H HS-CH2-C-COO-
NH3
cysteine
O H
H2N-C-CH2-CH2-C-COO-

NH3
O H
H2N-C-CH2-C-COO-
NH3
glutamine
asparagine
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Group III. Acidic side chains

• Based on having a pH of 7.

O H
-O-C-CH2-CH2-C-COO-
NH3
glutamic acid
O H
-O-C-CH2-C-COO-
NH3
aspartic acid
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Group IV. Basic side chains

• Based on a pH of 7.

lysine
H
arginine
histidine
N
H
N

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Group I amino acids are nonpolar and
hydrophobic. Groups II, III, and IV are polar
and hydrophilic.
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Polypeptides and proteins

• Proteins are polymers of amino acids.
• Peptide bond - chemical force (between -COOH of
  one a.a. and -NH3 of the other a.a) that links
  two a.a. together.

H2O
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 Polypeptides and Proteins   By convention, the
amino end (N-) is taken as the beginning of a
polypeptide chain, and so the sequence of a.a.
is written from N-terminus to C-terminus.   
The backbone of a polypeptide chain is always in
the order of C-C-N
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Peptides
N-terminal residue
C-terminal residue
H O - N - C - C -
H R
H O H2N - C -
C R
H N - C - COOH H R
peptide linkages
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Protein function

• Enzymes - biological catalysts.

• Immuno-globulins
• antibodies are made of proteins.
• Transport - carrier proteins move materials
  around -
• hemoglobin for O2.
• Hormones control metabolism.
• Support proteins are structure materials to
  provide
• 3-D frame work.

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Monomeric proteins Consist of a single
peptide Multimeric proteins consist of more
than one peptide chains
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Four levels of protein structure

• Primary structure
• The amino acids sequence of in a polypeptide.

• Secondary structure
• Regular repeating structure of primary
  structure
• (?-helix, ?-sheet)
• Tertiary structure
• ?-helix, ?-sheet fold up to form a more
  complex 3-D
• structure..
• Quaternary structure
• Two or more polypeptide chains associate
  to form
• a multisubunit molecule.

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Primary structure.
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?-Helix

• Polypeptide chain coils
• into a rod shaped spiral.
• The chemical force that
• stabilizes the structure
• is H-bonds.

•  

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?-Pleated sheets

• Many polypeptide chains line up to form a sheet.
• The chemical force between the polypeptide
• chains is also H-bonds.

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•  
• C. Tertiary Structure
• -helices and ?-sheets fold into a more complex
• three dimensional structure.

For example, myoglobin molecule 153 a.a. in
eight ? helices folded together.   Most
nonpolar, hydrophobic residues are buried
inside, most polar and hydrophilic amino acids
are located on the surface - a biologically
stable situation.  
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Myoglobin
Heme
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D. Quaternary structure More than one
polypeptide chains form a protein complex.
For example, hemoglobin is a protein with four
subunits, two ? sub units and two ? sub units.
Each of them is an independent polypeptide
chain.
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Hemoglobin
2 ? chains
4 heme
2 ? chains
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Forces involved in tertiary structure
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II. Nucleic Acids

• DNA Deoxyribonucleic acid,
• Serves as the Master Copy for most
  genetic information.
• RNA Ribonucleic acid (mRNA, rRNA, tRNA)
• They to transfer information from DNA to
  proteins.

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Genetic central dogma DNA ? RNA ? proteins ?
cell structure and function.
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DNA and RNA composition

• Both are polymers of nucleotides.
• Each nucleotide consists of a sugar - phosphate
• backbone with nitrogenous bases attached.

sugar
phosphate
base
Major difference is in the type of sugar and
bases used.
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Each nucleotide contains a pentose ring, a
nitrogen Base and a phosphate group.
Each is named based on the base and the number
of P groups.
C-1
C-4
C-3
C-2
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The nitrogenous bases
Purines
adenine
guanine
Pyrimidines
thymine
uracil
cytosine
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Differences between DNA and RNA 1. deoxyribose
in DNA lacks an O at C2.

• 2. Ntrogen base composition
• DNA AGTC
• RNA AGUC

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DNA structure

• The individual nucleotides are linked up to
• form the backbone
• of a polynucleotide
• chain.
• Each polynucleotide
• chain has a 5' end and
• 3 end.

Phosphodiester bond
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 DNA Double Helix (secondary structure) (Watson
and Crick 1953) Two polynucleotide chains coil
together to form right-handed helix. The N
base of opposite chains pair to one another and
form H-bonds G C and A T 
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• H-bonds is the major force to stabilize the
  helix.
• A-T and G-C pairing a purine must pair with
• a pyrimidine.
• The base pairing rule allows maximum number
• of H bonds to be formed.

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3
3
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• RNA
• The structure of RNA is chemically similar to
• DNA, but there are three fundamental differences
• between RNA and DNA

• RNA is single stranded.
• RNA contains ribose rather than deoxyribose.
• RNA uses uracil instead of thymine.

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Three forms of RNA

• Ribosomal RNA rRNA - Part of ribosome
• Messenger RNA - mRNA. Carries genetic
  information from DNA to protein.
• Transfer RNA - tRNA. Transport the
  appropriate amino acids to ribosome.

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Nucleic acids in different organisms Eukaryotic
cells Double stranded DNA coiled into
chromosomes. Single stranded RNA. Prokaryotic
cells Double stranded, circular DNA. There
is only one chromosome per cell compacted in an
area called nucleoid. Virus DNA single
stranded or double stranded RNA single
stranded or double stranded
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III. Carbohydrates (sugars) Building blocks of
polysaccharides are Monosaccahrides.
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 Biological functions of carbohydrates 1)   
Energy stock (starch and glycogen) Glucose is
the major biological fuel.
2)    Ribose and deoxyribose are the building
blocks of RNA and DNA.   3)    Some large
sugars (sellulose) are important structure
materials for plant and bacteria cell walls.
  4)    Can form glycoproteins or glycolipids.
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Types of carbohydrates

• Based on number of sugar units in the chain.
• Monosaccharides - single sugar unit
• Disaccharides - two sugar units
• Polysaccharides - more than 10 units

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Monsaccharides Also called simple sugars.
Most monosaccharides in nature contain 3 - 7
carbons trioses, tetroses, pentoses, hexoses,
and heptoses).
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According to where the carbonyl group is located,
monosaccharides can be divided into

• Aldose - polyhydroxyl aldehyde (aldehyde sugar)
• with the carbonyl group (CO) at the
• first carbon position, which forms an
• aldehyde group (CHO).
• Ketose - polyhydroxyl ketone (ketone sugar).
• Carbonyl group is at C2 position

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H CO
H-C-OH H-C-OH H-C-OH
CH2OH
CH2OH CO
HO-C-H H-C-OH
H-C-OH CH2OH
Aldose Ketose
(Based on location of CO)
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In glyceraldehyde molecule, the asymmetric
carbon, C2 is called a chiral center. There
can be two stereoisomers, the D and L forms.
Naturally existing glyceraldehyde is in the D
configuration.
H CO
H-C-OH CH2OH
Chiral center
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L- and D- glyceraldehyde
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Any other sugars with same configuration as
D-glyceraldehyde is classified as D sugar,
otherwise L sugar.
Most naturally occurred sugars are in their
D-forms. D-glucose, D- ribose (Amino acids ?)

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CH2OH CO
HO-C-H H-C-OH
H-C-OH CH2OH
H CO
H-C-OH CH2OH
D-glyceraldehyde D-fructose Only the
chiral center farthest from the carbonyl
determines the configuration of the sugar.
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D-glucose

• Glucose is an aldohexose sugar.

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Carbohydrates in cyclic structures

• Monohydrates with five C or more spend most
• of their time in cyclic structure.

? -D-glucose
Fischer vs. Haworth projections
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  Each cyclic sugar can have two stereoisomers,
? and ?.

• The position of -OH group on C-1
• ? sugar - OH group is under the plane.
• ? sugar - OH group is above the plane.

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? - D glucose is most stable in solution.
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Reactions of glucose and other monosaccharides

• Oxidation-Reduction. Required for their complete
  metabolic breakdown.
• Glycoside formation. Linkage of monosaccharides
  to form polysaccharides.
• Amino derivatives. Used to produce structural
  components and glycoprotein.

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1). Oxidation-reduction (redox) Reaction Redox
reaction of glucose is the most important part
of energy production.  
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In a redox reaction, if one reactant (glucose)
becomes oxidized (gaining an O atom or losing a
H), the other has to be reduced (loosing an O,
or gaining a H).
The molecule that gains O or loses H (glucose) is
called a reducing agent. The The molecule that
gains H or loses O is called an oxidizing agent.

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Reducing sugars are those that contain free
aldehyde group and are capable of reducing
metals ions (Cu).
The oxidizing agents, Benedicts reagent,
Tollen's reagent and Cu are used to identify
the presence of reducing sugars (urine
glucose).
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In aerobic respiration pathways, the enzyme that
catalyzes redox reactions is dehydrogenase, which
uses NAD and NADH as coenzymes.
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3). Amino Derivatives of Sugars When -OH group
of a carbohydrates is replaced by an amino group
? amino sugar.   Two naturally occurred amino
sugars are D-2-aminoglucose (glucosamine) and
D-2-aminogalactose (galactosamine).
Derivatives of glucosamine, N-acetylglusamine
and N-acetylmuramic acid, are two components of
bacteria cell wall.  
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• Functions of amino sugars.
• Structural components of bacterial cell walls.
• As a component of chitin, exoskeleton of some
  organisms.

• A major structural unit of chondroitin sulfate
  
• a component of cartilage (glucosamine).
• Component of glycoprotein and glycolipids.

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4). Glycoside Formation An O-glycosidic (R-O-R)
bond can be formed between two monosaccharides,
when two -OH groups react with each other. The
product is called a glycoside.  
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Glycoside formation

• ? or ? -OH group of cyclic monosaccharide can
  form link with another one (or more).
• glycosidic bond
• sugar -O- sugar
• oxygen bridge

O
O
OH
H
H
H
H
H
H
H
OH
OH
H
OH
OH
OH
H
OH
H
OH
O
H
H
H
O
H
H
OH
o
H
H
OH
OH
H
OH
OH
H
H
OH
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Two types of glycosidic bonds can be formed,
depending on the position of the C-1 OH (? or ?
configuration) ? glycosidic bond -
linkage between a C-1 ? OH and a C-4 OH ?
glycosidic bond - linkage between a C-1 ? OH
and a C-4 OH ? bonds
? bonds
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Disaccharides sucrose, lactose and manose, when
two monosaccharides are linked up by a
glycosidic bond
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Polysaccharides - Carbohydrate polymers Chains
of monosaccharides linked up by O-glycosidic
bonds. There are different polysaccharides
depending on the length degree of branching
sequence of the monosaccharides and types of
glycosidic bonds.  
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Functions of Polysaccharides

• Storage Polysaccharides
• Energy storage - starch and glycogen
• Structural Polysaccharides
• Provide protective walls or lubricative
• coating to cells cellulose
• Structural Peptidoglycans
• Bacterial cell walls

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1. Starch

• Energy storage in plants
• Long repeating chain of ?-D-glucose
• (up to 4000 units)

• Amylose is the major form of starch with straight
  chain that forms coils ? (1 4) linkage.

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Amylopectin

• Branched structure due to crosslinks.

? (1 6) linkage at crosslink
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2. Glycogen

• Energy storage of animals (animal starch).
• Stored in liver and muscles as granules.
• Highly branched polymer, similar to amylopectin.

? (1 6) linkage at crosslink
c
c
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 3. Cellulose Structural component of wood and
plant fibers. Cellulose is an unbranced polymer
of glucose linked up by ? (1?4) glycosidic bond.
 
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Many long cellulose chains lined up in a parallel
arrangement and associate with each other
through H-bonds. The bundles of cellulose
form strong and rigid frameworks that provides
physical support for plant cells. Bacterial
cell walls contain cellulose as well as
glucosamine derivatives.
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Glycoproteins

• Proteins that carry covalently bound carbohydrate
  units.
• Biological functions serve as cell surface
  marker to be involved in
• immunological protection
• cell-cell recognition
• blood clotting
• host-pathogen interaction

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III. Lipids Are not typical polymers that are
formed by monomer molecules. But are still
considered as macromolecules due to their large
molecular size. They form one major category of
organic materials in cells.
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Lipids are heterogeneous group of compounds
which are diverse in their structures and
functions. One common feature of all lipids is
their low water solubility. Lipids are mostly
hydrophobic, although some can be amphipathic
(polar and non polar regions).
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Micelle
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Major classes of lipids Triacylglycerols
(fats) energy storage Phospholipids -
membrane strucutre Steroids hormone and
membrane structure
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 A.   Triacylglycerol (fat) A triacylglycerol
molecule contains one glycerol portion and three
fatty acid chains. Fatty acid part varies
between different fat molecules.
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• Triacylglycerol

glycerol
H
O
H
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Fatty acids

• Long carbon chain with a carboxyl group at one
  end and a methyl (CH3) group at the other end.
• CH3(CH2)nCOOH

• Size Range C12 - C24 (most contain 16 -18
  C).
• Always an even number of carbon.
• Bonding between C may differ.
• Some have C atoms all linked with single
• bonds, others may contain double bonds.

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Saturated FA contain all single bonds between
carbons. (Each C has maximum number of H that
it can bind). Unsaturated FA contain one or
more double bonds between carbons.
Monounsaturated FA - only contain one double
bond in the molecule. Polyunsaturated -
many double bonds in the chain.  

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Saturated fatty acid
Unsaturated fatty acid
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B. Polar Lipids Including glycerophospholipids
(phospholipids) and sphingolipids.  

• Phospholipids are lipids that contain a phosphate
• group.
• Structure similar fat and is derived from
  glycerol (modified fat)
• The third fatty acid chain is replaced by a
  phosphate group.

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Phosphoglycerols
Lecithin phophatidyl-choline
H
O
O
C
C
H
O
C
H
O
C
O
-O-
O
CH2
P
-
O
Non-polar tail
Polar head
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• The phosphate portion is polar and is soluble
  in
• water (hydrophilic). It forms the "head" of
  the
• olecule.
• The nonpolar fatty acids are hydrophobic and
• form tails.
• All phospholipids have polar heads and nonpolar
  
• tails.

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Lecithin
Non-polar tail
Polar head
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Members of phospholipids a. Phosphatidic acid
an H atom is attached to the phosphate
group. b. Phosphatidyl choline X choline
group. c.Phosphatidyl serine X
serene. d.Phosphatidyl inositol X inositol, a
6C sugar.    
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Steroids

• Broad class of compounds that all have the same
  base structure.

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• Cholesterol is the best known steroid
• Forms cell membrane

• Also serves as precursor of steroid hormones
• (estrogen, testosterone, glucocorticoid) and
• bile salts.

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• Some reproductive hormones.

CH
3
C
O
CH
3
progesterone
CH
3
O
testosterone
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• Cortisone (glucocorticoid)
• Functions
• Regulates metabolism of carbohydrates Treatment
  of autoimmune diseases ...

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Other biological roles of Cholesterol

• Associated with hardening of the arteries.
• Appears to coat the arteries - plaque formation.

• Results in
• Increased blood pressure and
• Clot formation leading to heart attack and
  stroke