Download MB ChB PHASE I

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MB ChB PHASE I
THE MOLECULES OF
LIFE
LECTURE 1
AIM: To review:
the elements of life;
the roles of functional groups
and of molecular configuration and
conformation in biomolecular function;
the chemical reactions of life.
http://www.abdn.ac.uk/~bch118/index.htm
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Molecular
unity/simplicity
biological diversity/complexity,
underlie
i.e. the chemistry of life is similar in all
organisms.
This similarity is seen
at the elemental level;
at the molecular level;
in the kinds of reactions that occur.
[Life at the Molecular Level Lecture 1]
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ELEMENTS OF LIFE
Of ~90 natural elements,
~10
H C N O Na P S Cl K Ca
are structural parts of organisms,
and needed in man in gramme quantities
daily.
~12 other, ‘trace elements’ are needed in
very small amounts,
usually because they are essential parts of
particular proteins,
e.g. Fe in haemoglobin.
[Proteins Lecture 4]
In fact,
>99% mass of most cells consists of
H O N C.
Why these in particular?
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In general, light atoms form the strongest
bonds,
and these four are the lightest atoms able
to make 1, 2, 3 and 4 bonds respectively.
C is particularly versatile:
it can form stable
single bonds
single and double bonds
single, double and,
occasionally, triple bonds
with
with
H
O, N
with
other C’s.
This bonding capacity and versatility
must
underlie
the
evolution
of
combinations of these elements into
biomolecules.
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‘FUNCTIONAL GROUPS’ DEFINE
BIOMOLECULAR FUNCTION
Many biomolecules can be thought of as
derivatives of hydrocarbons,
i.e. molecules with
a C backbone,
to which H atoms are attached:
H
---C
H
H
C
H
H
C--H
H’s may be replaced by ‘functional
groups’,
i.e. groups having particular chemical
reactivity,
e.g.
-OH, -CHO, -C O, -C-OH, -NH2
O
etc.
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Biomolecular function depends in part on
the presence of particular ‘functional
groups’,
e.g. epinephrine function requires the
presence of hydroxyl
phenyl and
secondary amino groups.
[C&H, p. 286]
Function also depends on how the groups
are arranged in space:
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ROLES OF MOLECULAR CONFIGURATION
AND CONFORMATION IN BIOMOLECULAR
FUNCTION
‘Configuration’ = the fixed arrangement
of atoms in a molecule.
Many
biomolecules
arrangement
C
C
contain
the
Groups on either side of the rigid double-bond
cannot rotate, relative to each other.
This means that two, distinct configurations
can occur:
X
C
C
X
C
X
‘cis’
C
X
‘trans’
The two can only be inter-converted by
breaking and re-forming bonds.
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This configurational difference can be
important biologically:
e.g. in the retina,
light triggers
cis-retinal
trans-retinal,
which then triggers a nerve impulse to the
brain.
Similarly,
many biomolecules contain C’s that have
four different groups attached.
This arrangement can also occur in two,
distinct configurations, because of the
tetrahedral valency of C.
E.g., for an amino-acid:
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Such a C is said to be ‘asymmetric’ or
‘a chiral centre’.
The two forms, L- and D-,
(so-called because the two forms of glyceraldehyde
rotate polarised light in opposite (laevo and dextro)
directions)
again are inter-convertible only by
breaking and re-forming covalent bonds.
Again, the configurational difference can
be important biologically:
e.g. only L-amino-acids occur in proteins.
[Proteins Lecture 1]
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‘Conformation’ = the precise, detailed
arrangement of atoms in a molecule.
A molecule containing bonds around
which atoms/groups can rotate may exist
in many, different conformations.
These are inter-convertible without
breaking and re-forming covalent bonds
(unlike different configurations).
Some conformations may be more stable
than others.
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Thus, many biomolecules contain
C
C
bonds, around which attached groups can
rotate almost totally freely:
although interactions of X, Y etc
with other groups in the molecule
may restrict rotation,
and make some conformations more stable
than others.
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In summary,
the presence of functional groups,
and their arrangement in space produced
by the configurations
and conformations of a biomolecule,
determine the overall ‘personality’ of the
biomolecule,
i.e.
how it interacts with other molecules,
and, hence, its function.
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THE CHEMICAL REACTIONS OF LIFE
There are five kinds.
1 Redox reactions
reduction = gain of electrons
oxidation = loss of electrons.
Every reduction is accompanied by an
oxidation (and vice-versa).
oxidised X
reduced Y
e
e
reduced X
oxidised Y
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Oxidations (in isolation) are exergonic,
reductions
endergonic.
[Life at the Molecular Level Lecture 2]
In many biological redox reactions,
two electrons (and two protons)
are gained/lost,
[‘… H atoms, with their ‘high energy’ electrons,
are stripped off, 2 at a time …’
Life at the Molecular Level Lecture 2]
i.e. two hydrogen atoms are transferred.
Such reactions are called ‘dehydrogenations’
and are catalysed by ‘dehydrogenases’.
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e.g.
2e 2H+
-
-
lactate
pyruvate
NAD+
NADH + H+
OCO
HOCH
CH3
OCO
C O
CH3
2e 2H+
Flow through this reaction,
catalysed by lactate dehydrogenase,
may be in the direction shown
or be reversed,
depending on cellular conditions.
[Energy Transformations - Carbohydrates Lecture 4]
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Reactions that cleave and form C C
bonds
e.g. cleavage of the food material glucose
in the catabolic pathway ‘glycolysis’:
glucose
(6-C)
fructose 1,6-bisphosphate
(6-C)
aldolase
3-C molecule
3-C molecule
[Energy Transformations - Carbohydrates Lecture 4]
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Internal rearrangements
e.g., also in glycolysis, a rearrangement
occurs in preparation for the aldolasecatalysed reaction:
glucose 6-phosphate
fructose 6-phosphate
H
H C C CCCC
O O
H
H
H C C CCCC
O O
H
[Energy Transformations - Carbohydrates Lecture 4]
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Group transfers
e.g., also in glycolysis:
fructose
6-phosphate
ATP
fructose
1,6-bisphosphate
ADP
In this reaction,
in which a phosphate group is transferred,
ATP dephosphorylation
supplies energy input
in preparation for the aldolase-catalysed
reaction.
[Energy Transformations - Carbohydrates Lecture 4]
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Condensations and hydrolyses
e.g.
the monomeric sub-units of
proteins,
polysaccharides,
and nucleic acids
are all joined by condensation,
and broken by hydrolysis.
-X-OH
H-Y-
H2O
H2O
-X-Y-
[Proteins; Energy Transformations - Carbohydrates;
Storing and Using Genetic Information Lectures]
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MB ChB PHASE I
THE MOLECULES OF
LIFE
LECTURE 2
AIM: To review:
the molecular composition of cells;
the polymeric structure of
[proteins],
nucleic acids,
carbohydrates,
and lipids.
[C&H, pp. 83-86, 181-182, 188, 201-203, 291-292,
395-398.]
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THE MOLECULAR
OF CELLS
COMPOSITION
Water and biopolymers
components of cells.
are
major
E.g. in Escherichia coli:
%
~ no. of
total different
weight molecular
species
Water
Proteins
DNA
RNA
Polysaccharides
Lipids
Monomeric sub-units and
intermediary metabolites
Inorganic ions
70
15
1
6
3
2
1
3000
1
>3000
5
20
2
1
500
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Proteins
are polymers of amino-acid monomers
linked by peptide bonds.
[Proteins Lecture 1]
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2 Nucleic acids
are polymers of nucleotide monomers
linked by 3’, 5’-phosphodiester bonds.
A nucleotide = N/C-containing ‘base’
+ pentose (5-C sugar)
+ 1 or more phosphates.
There are 2 kinds of ‘base’ in nucleic acids:
pyrimidines
(flat, single rings)
cytosine (C)
thymine (T)
uracil
(U)
purines
(~ flat, double rings)
adenine
guanine
[Learning Guide, p.
(detailed structures for reference only)]
(A)
(G)
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RNA contains mainly
DNA
mainly
A G C U,
A G C T.
There are two pentoses in nucleic acids:
D-ribose
2-deoxy D-ribose
[Learning Guide, p.
Note: 1
2
(in RNA)
(in DNA)
]
numbering of C atoms;
why the latter is called ‘deoxy’.
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A nucleoside =
base
+
pentose.
=
adenine
+
D-ribose
E.g.
adenosine
[Learning Guide, p.
]
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Other nucleoside names:
[Learning Guide, p.
]
base
D-ribose
2-deoxy D-ribose
adenine
guanine
cytosine
thymine
uracil
adenosine 2’-deoxyadenosine
guanosine 2’-deoxyguanosine
cytidine
2’-deoxycytidine
(2’-deoxy)thymidine
uridine
Note:
1 nucleoside names are used in naming
nucleotides;
2 deoxyribose is
but deoxyribonucleosides are
2 -deoxy,
2’ -deoxy
because in the nucleoside,
the pentose C numbers change
from 1-5 to 1’-5’,
so that they’re different
from those of the ring atoms of the base;
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3 the anti-HIV drug AZT is a nucleoside
analogue.
[Tutorial 4 Question 4]
Biological nucleotides are mainly
nucleoside 5’-phosphates,
e.g. adenosine 5’-monophosphate.
[Learning Guide, p.
]
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Abbreviations:
adenosine 5’-monophosphate
Similarly,
= AMP.
GMP,
CMP,
etc;
and
2’-deoxyadenosine 5’-monophosphate =dAMP.
Similarly,
dGMP,
dCMP,
etc.
With >1 phosphate is present,
adenosine 5’-diphosphate
Similarly,
= ADP.
ATP
dADP
GTP
dCDP
etc.
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Nucleotide monomers are linked by 3’, 5’phosphodiester bonds.
[Learning Guide, p.
Note:
]
1
it is DNA (rather than RNA);
2
the 3’, 5’-phosphodiester bonds;
3
the 5’ and 3’ ends;
4
a simple way to represent the
polymer.
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A (brief) statement of the Watson-Crick
model of DNA:
two DNA polymers wind about a common
axis to form a double-helix;
[Learning Guide, p.
]
the model involves:
specific base complementarity;
an antiparallel arrangement of the two
polymers.
The model is most stable when
A on one polymer is opposite T on the
other and
G on one polymer is opposite C on the
other.
A and T,
G and C are therefore
‘specific, complementary bases’.
A and T are linked by
G and C
by
hydrogen bonds.
2, and
3
[Water Lecture 1; Learning Guide, p.
]
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The model is most stable when the two
polymers are antiparallel
(run in opposite directions).
[Learning Guide, p.
Note:
]
1
the antiparallel arrangement;
2
a simple way to represent it.
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Polysaccharides
are polymers of sugar monomers linked
by glycosidic bonds.
e.g.
starch, glycogen are polymers of
D-glucose (6-C).
[Energy Transformations - Carbohydrates Lecture 1]
D-glucose is:
CHO
HCOH
OHCH
HCOH
HCOH
CH2OH
C
1
2
3
4
5
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C’s 2-5 are all asymmetric;
[Lecture 1]
the arrangement around C5 makes the
sugar shown
D-glucose.
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The O attached to C5 can bridge between
C5 and C1, producing a cyclic form:
In solution, linear and cyclic forms interconvert.
The linear (but not cyclic) form
has an aldehyde group, which can be
oxidised in a reaction
in which something else is reduced,
so glucose is a ‘reducing sugar’.
A polymer is formed by condensation:
[Lecture 1]
glucose-OH
HO-glucose
H2 O
glucose-O-glucose
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In glycogen and starch, the ‘LHS’ (as
indicated in the previous diagram) of a
glucose monomer is linked to another
glucose monomer.
The link locks that additional glucose in
the cyclic form.
When many monomers link together, all
are locked,
except one at the end of the polymer,
which forms a ‘reducing end’.
[Energy Transformations – Carbohydrates Lecture 1]
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4 Lipids
usually contain one or more
long-chain carboxylic (fatty) acids
e.g. CH3(CH2)14COOH,
which may be ‘saturated’ (as above)
or ‘unsaturated’
i.e. contain C
C bonds.
Triacyglycerols (triglycerides)
are storage lipids
consisting of three fatty acids
esterified to glycerol:
3 fatty acids
+
H2C - OH
H C - OH
H2C - OH
O
H2C - O - C - hydrocarbon chain
O
HC - O - C - hydrocarbon chain
O
H2C - O - C - hydrocarbon chain
glycerol
triacylglycerol
3 H2O
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Simple phospholipids have a similar
structure,
but with a ‘head group’ attached to one of
the - OH’s of the glycerol:
fatty acid
long
hydrocarbon
‘tail’
glycerol
skeleton
fatty acid
O
O - P - O – various structures
O‘head group’