Transcript Biological monomers and polymers (1)

1. Chemical reactions in cells
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Thousands of biochemical reactions, in which metabolites are
converted into each other and macromolecules are build up, proceed
at any given instant within living cells. However, the greatest
majority of these reactions would occour spontaneously at
extremely low rates.
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For example, the oxidation of a fatty acid to carbon dioxide and water in a test
tube requires extremes of pH, high temperatures and corrosive chemicals. Yet
in the cell, such a reaction takes place smoothly and rapidly within a narrow
range of pH and temperature. As another example, the average protein must be
boiled for about 24 hours in a 20% HCl solution to achieve a complete
breakdown. In the body, the breakdown takes place in four hours or less under
conditions of mild physiological temperature and pH.
How can living things perform the magic of speeding up chemical
reactions many orders of magnitude, specifically those reactions
they most need at any given moment?
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
2. Introducing enzymes
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The ENZYMES are the driving force behind all biochemical
reactions happening in cells.
Enzymes lower the energy barrier between reactants and products,
thus increasing the rate of the reaction.
Enzymes are biological catalysts. A catalyst is a species that
accelerates the rate of a chemical reaction whilst remaining
unchanged at the end of the reaction. Catalysis is achieved by
reducing the activation energy for the reaction.
Enzymes can catalyse reactions at rates typically 106 to 1014 times
faster than the uncatalysed reaction.
Enzymes are very selective about substrates they act upon and also
where the chemistry takes place on a substrate.
Both the forward and reverse reactions are catalysed. A catalyst
cannot change the position of thermodynamic equilibrium, only the
rate at which it is attained.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
3. Enzymes are proteins
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Enzymes are composed of proteins, and
proteins are long polymers of amino acids.
Amino acids all have this general formula:
Amino acids have two functional groups (aminic and carbossilyc),
which can react together forming covalent bonds called peptide
bonds, so that they are linked head-to-tail.
The side chain, or R group, can be anything from a hydrogen atom
(as in the amino acid glycine) to a complex ring (as in the amino
acid tryptophan).
Each of the 20 amino acids known to occur in proteins has a
different R group that gives it its unique properties.
The linear sequence of the amino acids in a polypeptide chain
constitutes the primary structure of the protein
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
4. Four levels of structure of the proteins
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The primary structure of a protein is the sequence of amino acids in its
polypeptide chain.
The secondary structure is the regular arrangement of amino acids within
localized regions of the polypeptide. Two types of secondary structure are
particularly common: the a helix and the b sheet. Both of these secondary
structures are held together by hydrogen bonds between the CO and NH
groups of peptide bonds.
Tertiary structure is the folding of the polypeptide chain as a result of
interactions between the side chains of amino acids that lie in different
regions of the primary sequence. In most proteins, combinations of a
helices and b sheets, connected by loop regions of the polypeptide chain,
fold into compact globular structures called domains, which are the basic
units of tertiary structure.
The fourth level of protein structure, quaternary structure, consists of the
interactions between different polypeptide chains in proteins composed of
more than one polypeptide. Hemoglobin, for example, is composed of four
polypeptide chains held together by the same types of interactions that
maintain tertiary structure.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
5. The active site
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Enzymes are typically large proteins, which are structured
specifically for the reaction they catalyze. Their size provide sites
for action and stability of the overall structure.
Two important sites within enzymes are:
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The catalytic site, which is a region within the enzyme involved with
catalysis, and
The substrate binding site which is the specific area on the enzyme to which
reactants called substrates bind to.
The catalytic site and substrate binding site are often close or
overlapping and collectively they are called the active site.
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If the catalytic site is not near the substrate binding site it can move into
position once the enzyme is bound to a substrate.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
6. The “Lock-and-key” metaphor
Schematic representation
of the action of a
hypothetical enzyme in
putting two substrate
molecules together. (a) In
the "lock-and-key"
mechanism the substrates
have a complementary fit
to the enzyme's active
site. (b) In the induced-fit
model, binding of
substrates induces a
conformational change in
the enzyme.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
7. Aditional components of enzymes
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Often enzymes require additional components to become
active. These may be:
 co-factors: simple cations, or small organic or
inorganic molecules that bind loosely to the enzyme,
 prosthetic groups: similar to co-factors but more
tightly bound to the enzyme, or
 co-enzymes – which are more complex than co-factors
and prosthetic groups, they often act as a second
substrate or bind covalently with the enzyme to affect
the active site.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
8. The first step of photosynthesis
Photosynthesis. The key passage of the photosynthesis is the organication of the
carbon, or the fixation of CO2 .
The CO2 molecule condenses with ribulose 1,5-bisphosphate to form an unstable
six-carbon compound, which is rapidly hydrolyzed to two molecules of 3phosphoglycerate.
This reaction is catalyzed by the enzyme ribulose 1,5-bisphosphate
carboxylase/oxygenase (RUBISCO)
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
9. An enzyme of fundamental importance for life
The enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RUBISCO) is located
on the stromal surface of the thylakoid membranes of chloroplasts. It comprises eight
large (L) subunits (one shown in red and the others in yellow) and eight small (S)
subunits (one shown here in blue and the others in white).
The active sites lie in the L subunits. Each L
subunit contains a catalytic site and a
regulatory site. The S chains enhance the
catalytic activity of the L chains. This enzyme
is very abundant, constituting more than 16%
of chloroplast total protein. RUBISCO is
probably the most abundant protein in the
biosphere.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
10. The active site of RUBISCO
Structure of the catalytic domain of the
active form of ribulose 1,5-bisphosphate
carboxylase.
Dark blue cylinders represent a helices
and yellow arrows represent b sheets in the
polypeptide. The key residues in the active
site are carbamylated lysine 191, aspartate
193, and glutamate 194; a Mg2+ ion is
bound to carbamylated lysine 191. The
substrates CO2 and ribulose 1,5bisphosphate are shown bound to the
active site.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
11. METABOLIC PATHWAYS
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There are thousands of enzyme-catalyzed reactions in a cell. If the
biochemical reactions involved in this process were reversible, we would
convert our macromolecules back to metabolites if we stop eating even for
a short period of time.
To prevent this from happening, our metabolism is organized in metabolic
pathways. These pathways are a series of biochemical reactions which
are, as a whole, irreversible.
These reactions are organized in consecutive steps or pathways where the
products of one reaction can become the reactants in another. Every
biochemical molecule is synthesized in a biochemical pathway with
specific enzymes.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
12. Metabolic pathways of phenylalanine in human
One small part of the
human metabolic
map, showing the
consequences of
various specific
enzyme failures.
(Disease phenotypes
are shown in colored
boxes.)
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini
13. Phenylketonuria
Phenylketonuria is caused by an absence or deficiency of phenylalanine hydroxylase or,
more rarely, of its tetrahydrobiopterin cofactor. Phenylalanine accumulates in all body
fluids because it cannot be converted into tyrosine. Normally, three-quarters of the
phenylalanine is converted into tyrosine, and the other quarter becomes incorporated
into proteins. The accumulation of phenylpyruvate leads to severe mental retardation in
infants. If the high level of phenylpyruvic acid is detected soon after birth, the baby can
be placed on a special low-phenylalanine diet and develops without retardation.
Because the major outflow pathway
is blocked in phenylketonuria, the
blood level of phenylalanine is
typically at least 20-fold as high as in
normal people. Minor fates of
phenylalanine in normal people, such
as the formation of phenylpyruvate,
become major fates in
phenylketonurics.
Genetica per Scienze Naturali
a.a. 06-07 prof S. Presciuttini