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Biochemistry revision:
Carbohydrates:
Carbohydrates are organic molecules based upon the molecular formula (CH2O)n but can
have other elements like nitrogen, phosphorous and essentially homologues of triose
glyceraldehyde:
• Triose Glyceraldehyde
• Tetrose Erthrose
• Hexose Glucose
First we must consider the phenomenon of isomerism
...

Optical isomerism:
Optical isomerism occurs when there is an asymmetric carbon atom
...
As is found in the case of Triose
Glyceraldehyde
...

Thankfully not all are important in nature and only a few have to be learned
...


!

!
!
!
Properties of sugars:
It’s obvious that to a large extent, the properties of sugars are going to reflect the properties
of aldehydes (or ketones in the case of fructose)
...

A property of an aldehyde is that it can condense with 2 molecules of alcohol to form a
compound called acetal
...

Hemi-acetals can take up a second alcohol to form the full acetal
...
Which particular carbon atom depends on the
bond lengths and angles, the c-5 atom is appropriate
...

There are therefore 2 forms of D-Glucose called α (alpha) and β (beta) respectively
...
e
...

Other ring structures are found in fructose and the five-carbon sugars of ribose and
deoxyribose
...
If the group is another sugar, then
polymerisation is possible
...
Thus, two molecules of glucose
may condense to form the disaccharide maltose
...
In such a chain, the end with the “free” –OH on the
C1 is called the “reducing end”
...

A chain compromising up to eight molecules of a monosaccharide is called an
oligosaccharide
...


You can see that isomaltose has one reducing end, and 2 non-reducing ends
...
The branched polysaccharide is called amylopectin
...
Not that, despite the high degree of branching, there is only one reducing end
...
The alpha linked is easily
hydrolysed and the resulting glucose can enter
metabolic pathways to release energy
...

•One mechanism that aids this is conjugation i
...
the
addition of α-D-Glucuronic acid to a zenobiotics
...

•Such implications for drugs are obvious: High metabolism
– decrease in concentrations-resulting in the administration
of higher doses
...
They have an amino acid – NH2 group
(instead of an –OH group) on C2
...


Lactose

In general the β link is more stable than the α-link, more difficult to hydrolyse and, when
polymerised, forms stable “structural polysaccharides”
...

This is the structural polysaccharide in plant cell walls
...
e
...

In animals, complex β linked polysaccharides (sometimes with acetal, sulphate of phosphate
side-groups) form structural materials of cartilage, tendons and also lubricating fluids in
joints like synovial fluid; also anti-coagulant heparin
...


Hyaluronic acid repeating
dimer
...

Chondroitin is similar in structure to hyaluronic acid, except that the amino sugar is N-acetal
galactosamine
...
Sulphur esters (“chondroitin sulphate”) at the
C4 and C6 positions of the amino sugar are major structural components of cartilage,
tendons and bones
...
The original definition is that they make a translucent ‘grease spot’ on filter
paper
...

• Oils can be ‘hardened’ by hydrogenation of the unsaturated bonds
...
These avoid the longer chain fatty acids and
cholesterol found in animal fats e
...
butter
...
They tend to be more
stable and have higher melting points, are highly hydrophobic and form the water resistant
products like cuticles of insects, and in preen glands of birds (water off a ducks back)
...
g
...

Hydrolysis gives fatty acids, glycerol and other products, e
...
Phosphate
...
Triacylglycerol’s (triglycerides): a fuel store of the body (fat)
...
Phospholipids: crucial constituents of biological membranes
...
Steroids: cholesterol and bile function
4
...

Upon hydrolysis, fats and oils yield fatty (aliphatic) acids and glycerol
...
e
...

Fatty acids (a homologue of acids: acetic, ethanoic) are characterised by an alkyl chain with
a terminal carboxyl group
...

CH3(CH2)nCOOH
The hydrophobic side chain is typically depicted by ‘R’:
R – CH2 – COOH

Fatty acids are esterified to glycerol to make a fat
...


Saturated:
Since glycerol is a simple molecule:

!

And is common to all fats, the variation between fats is due to variation in the fatty acids
...

• They are separated by a methylene group (-CH2-) if more than one double bond
appears in a chain
...

• Cis conformations introduces a ‘kink’ in the chain preventing orderly packing of
chains and consequently lower the melting point of unsaturated fatty-acid
containing lipids and increasing their fluidity
...

• Branched-chain fatty acids are also found in some animals, including humans
...

However, there are variations and there are unsaturated, branched and even cyclic ones in
nature, e
...
unsaturated oleic acid
...
Most of the fatty acids needed are synthesised in vivo (within the cell) but
there are a few which need to be supplied by the diet, e
...
trans-ximenynic acid:
CH3 – (CH2)5 – CH
H – C – C ≡ C – (CH2)7 – COOH
Phospholipids:
Abundant in all biological membranes
...
This is formed by esterifying two of the
hydroxyls on glycerol with a fatty acid (same or different), whilst the third has phosphoric
acid
...

Choline

HO – CH2 – CH2 – NH3+ β-ethanolamine
HO – CH2 – CH – NH3+ Serine




COO-

Lecithin is formed when choline is esterified to the phosphate
...
An enzyme, lecithinase, hydrolyses off the
fatty acid on the β-carbon leaving the product Isolecithin, found in snake venom
...

Steroids:
The biochemist Chevreul found that in animal fats, there was a small residue that could not
be saponified (process which produces soap)
...
g
...

The structure of steroids is based on the three ringed compound
perhydrocyclopentanophenothrene
...


Hydroxyl group (-OH)

The properties of cholesterol depend on the properties of the functional groups:
1
...

2
...

3
...

In vivo, cholesterol is not especially active
...
However, its derivatives are important
...

Excretion is via the liver and gallbladder into the intestine as bile acids
...
This
group is esterified, usually with one of two amino acids (reacting with the amino group or
glycine or taurine) to form a peptide link
...


The sodium salts of these

The function of bile acids are as detergents
...
They are excreted into the bile and help
emulsify (render them soluble) fats prior to digestion
...

Eicosanoids:
1930’s a substance contained within semen caused contraction of smooth muscle tissue,
hence the substance, believed to originate in the prostate, and was termed prostaglandin
...

Eicosanoids consist of prostaglandins, thromboxanes and leukotrienes
...

•
•

Eicosanoids are produced in inflammatory responses and conditions to function as
potent inflammatory signalling molecules
...


Amino Acids and Proteins:
There are around 20 amino acids that are found in proteins (and several more which are
not)
...

An exception is the simplest (glycine) all have an asymmetric carbon atom and therefore
form optical isomers and have D and L forms
...
these amino acids that
can’t be synthesised by the human body are called essential amino acids
...

Properties:
The properties reflect the properties of the side chains
...

A compound like this (not only amino acids), which has two
ionisable groups (acidic and basic groups) that cancel each
other out, is called a zwitterion
...


pH

Alkaline
Amino acids become
Neutral
basic
...


High

The peptide bond:
Two amino acids may condense through the carboxylic acid group of one amino acid and
the amino acid and the amino group of another, with the elimination of water
...

The dipeptide can condense with
further amino acids at each end to
form oligopeptides and polypeptides
...

Although the ionisation of the amino
acid and carboxyl groups involved in
the peptide bonds is impossible,
polypeptides can carry charges due
to the ionisable groups on the side
chains
...

Low pH (acid) promotes the ionisation of the –NH3+
High pH (alkaline) promotes the ionisation of – COOWhatever the balance of NH2 and COOH in the side chains, there is a particular pH at which
there is an overall net neutral charge
...

Disulphide bridges:
In proteins, polypeptide chains can be joined together by the formation of one or more
disulphide bridges by means of pairs of cysteine molecules being oxidised to cysteine
...


Primary structure:

The linear configuration of the amino acids in a protein, together with any disulphide
bridges, is referred to as the primary structure
...

Is there some organisational structure imposed upon simple primary structure??
A clue came from the behaviour of keratin (hair)
...
The β is about twice as long as the α
...

Additional evidence is that many proteins are soluble, suggesting a globular structure with
the hydrophilic groups on the outer surface
...
g
...

William (bill) Astbury and Linus Pauling suggested that because proteins are so easily
disrupted, whatever forces were involved in stabilising the secondary structure must be
weak
...
and are probably not covalent
...
These were elucidated to explain the phenomena such as
the apparent doubling of the molecular mass of compounds like formic acid
...


!
Hydrogen bonds could form within, or between polypeptide chains
...

But it doesn’t explain the detail of the structure – only that H-bonds are involved
...
Hydrogen bonding exists only between –NH and O=C bonds as described
...
Bond angles were consistent with those in smaller molecules
...

However, the secondary structure doesn’t explain the properties of globular proteins
...
To account for this
we have to consider how the coiled thread might be further folded or configured into a
globular structure
...
Disulphide bridges –SH
...
H (hydrogen)-bonding
...
Ionic attraction between –COO- and –OH (e
...
on serine)
...
Ester links between –COOH and –OH (e
...
on serine)
...
Van der Waals forces
...

It’s largely upon the tertiary structure that the properties of the protein depend, because it’s
the tertiary structure that controls which functional groups are exposed for activity
...
Some protein molecules comprise aggregations of
globular polypeptide units
...


Nucleic acids and bases:
Carbohydrate macromolecules (e
...
starch or cellulose) are
polymers of a monosaccharide (e
...
glucose)
...
Nucleic acids
are polymers of units called nucleotides
...

What is a nucleotide?
A nucleotide is a unit that contains three components:
a) A 5-carbon sugar (pentose)
b) A nitrogenous base (purine or pyridamine)
c) A phosphate group
There are 2 pentoses:
• Ribose
• Deoxyribose
The same pentose is used throughout a particular nucleic acid
...
The 2 types found in
nucleic acids are adenine and guanine
...


A nucleoside is the dimer that’s formed when one of the pentoses is linked
on the nitrogenous bases
...

Thus Adenosine and guanosine, but “isine”, ion “uridine” (RNA) and thymidine (DNA)
...
The phosphate forms an ester
with the hydroxyl group on the C5 carbon atom of the pentose
...
In
the case of adenosine, we get AMP, ADP and ATP, respectively
...
This is called 3’ 5’ phosphate diester link
...
It’s easy to imagine that if the 2 strands peeled apart, a second complementary
strand whose sequence is prescribed by the template can be synthesised alongside, thus
giving a simple mechanism of replication of genetic material
...

RNA:
In RNA, the pyrimidine base thymine is replaced by uracil
...

DNA exclusively, and RNA are found in the nucleus of the cell
...
Each form has a different function
...

DNA transcription:
DNA directs its own replication aswell as its transcription by forming a complimentary RNA
strand (messenger RNA)
...

NAD+:
NAD+ is important as an enzyme cofactor, it can accept a pair of electrons to become
reduced to NADH + H+
...


Enzymes:
Characteristics:
1
...
Specificity
3
...
The reactants upon which enzymes catalyse a reaction are called substrates
5
...
So enzymes are not the sole domain of proteins
...

Catalyses the hydration of CO2 from tissues to the blood system to alveolar air
...
This is 107 times faster than the uncatalysed
reaction
...

In vitro, they behave slightly different but none the less makes them more suitable for
scientific investigation than proteolysis
...

• Trypsin: specific – peptide bond cleavage – only on the carboxyl side of lysine and
arginine residues
...

Enzymes are biological catalysts and are almost universally composed of:
1
...
A non-protein (co-factor) or prosthetic group (for example, a haem unit)
...

Apoenzyme + prosthetic group = holoenzyme

Enzymes differ from inorganic catalysts:
• They are more specific
...
One molecule of enzyme reacts with one molecule of substrate
reversibly
...

E + S ↔ ES
ES ↔ Products
The presence of an enzyme is detected by the reaction it catalyses and its activity is defined
as the rate of velocity, V, of the reaction
...
Usually µmol min-1
...

• Specific activity – is a measure of purity: activity (product formed) per mg of enzyme
present
...
g
...
1cm3 of enzyme preparation (removed from a stock
bottle containing 10cm3) was found to convert 30 µmol of substrate in 10 minutes
...
1cm3
...

Basic procedures:
The reaction is to be measured takes place in an incubation mixture
...
g
...

The enzyme is normally added last, and this starts the reaction time = 0 (time zero)
...
g
...
g
...
A time plot is constructed – it’s easier to think in
terms of a product produced
...

b) Enzyme might be becoming inactivated
...

d) Product or catalysis may be inhibitory to the enzyme
...
At any point on the curve is the rate, but this is
constantly changing
...
Construct a tangent to the
curve through t = 0 and the slope of the tangent is defined as the activity (rate = v)
...
For example, if a reactant (substrate or
Min
product) absorbs uniquely at a specific wavelength, the reaction can take place in a cuvette
of a spectrophotometer and the curve plotted out and the activity are calculated by a
computer
...
Remember that each point on a graph represents the
slope of the tangent at t = 0 for a time curve
...
Enzymes, being proteins, are also
affected and denatured by heat, a temperature curve rises to start with, to a maximum, and
then drops steeply as the enzyme denatures
...
g
...

Acid conditions promote the ionisation of amino groups (-NH4-) and alkaline conditions
promote the ionisation of carboxylic groups (-COO-)
...
The most favourable pH value – the point
where the enzyme is most active – is known as the optimum pH
...

However, In the case of an enzyme, the enzyme is present in limiting quantities
...

Phosphorylation:
Phosphorylated
Dephosphorylated
Phosphorylation of proteins is the key to cell signalling
...

The kinase Is an enzyme that will phosphorylate a protein (utilising ATP) and thus bring
about a change in conformation (ion channel) and the active site (enzyme)
...

+ ATP à

P + ADP

The biochemist Michaelis and Menton modelled the kinetics of the effect of substrate
concentration, leading to a derivation of the Michaelis Constant, Km
...

Thus enzyme-kinetics is the study of rates of enzyme-catalysed reactions
...

The basic equation is: E + S ↔ ES ↔ E + P
Alleosteric enzymes:
Not all enzyme kinetics observes M-M kinetics
...
Those enzymes with multiple subunits and multiple
active sites
...

Lineweaver-Burk plot:

“to estimate the maximal velocity (Vmax) and Michaelis constant (Km), to draw a simple plot of
V against [S] is correct, and try to read off these values from the graph
...
Instead, a LineweaverBurk plot (‘double reciprocal plot’) is used, from which it’s much easier to estimate these
values”
Transform to a straight line plot
...

The total energy of a system and its surroundings is constant
...
Merely different forms:
Heat (kinetic) – the random motion of molecules
Potential – the likelihood of chemicals reacting, i
...
petrol and oxygen
...

•
•
•

Change (Δ) in entropy (S) of the system = ΔSsystem
If heat flows from the system to surroundings:
o Then the system heat content (Enthalpy, H) will be reduced ΔHsystem
o Entropy of the surroundings will increase
...


System

System

Surroundings

Surroundings

Change in entropy is proportional to the amount of heat transferred from the system and
inversely so to the temperature (T) of the surroundings
...
Therefore a change in entropy
(surroundings) is: ΔSsurroundings = ΔHsystem/T
•
•
•

Total entropy change: ΔStotal = ΔSsystem + ΔSsurroundings
Substituting 1 into 2: ΔStotal = ΔSsystem + ΔHsystem/T
Multiplying by –T gives: -T ΔStotal = ΔHsystem – T ΔSsystem

-T ΔStotal = ΔHsystem – T ΔSsystem
-TΔS = has units of energy and is termed free energy, or Gibbs free energy, ΔG:
ΔG = ΔH – TΔS
The free energy must be negative for a process to occur spontaneously
...

Some with an energy output – exergonic (-ΔG)
...

In principle then, some of the energy released by an exergonic reaction can be captured to
drive an endergonic reaction
...

Exergonic reaction – one in which energy is released (products have less chemical energy
than reactants)
...

Endergonic reaction – one in which energy must be supplied for the reaction to occur,
products have more chemical energy than reactants
...
This can be determined
experimentally then:
ΔGO = -rt Ink
A reaction may therefore be in the form:
Glucose-6-phosphate + H2O à Glucose + Phosphate ΔGO = -14 KJ/mol-1
In plain word, when a mole of Glucose-6-phosphate is hydrolysed, the reaction proceeds
with the release of 14KJ per mole of substrate converted
...

b) “universal energy currency”
There are no enzymes that can catalyse the direct transfer of phosphate groups
from, for example, PEP to glucose
...

It is feasible thermodynamically, but not possible enzymatically
...
Let us imagine that we need to synthesise Glucose-6phosphate, with PEP as an energy source
...

Coupling works by the principle of the common intermediate
...
From the free energy change we should anticipate that’s its oxidation to carbon dioxide

and water should proceed spontaneously
...
The hump is called the activation
energy [E], and is removed (or reduced) in the presence of a catalyst (e
...
an enzyme)
...

Intermediary metabolism:
Oxidation describes the loss of electrons by a molecule, atom or ion
Reduction describes the gain of electrons by a molecule, atom or ion
...

Oxidised compounds
Reductant (NADH) à Product + e- (NAD+ + FAD)
Products have little energy and are referred to as compounds with a HIGH redox potential
...
Those that convert energy from fuels into biologically useful forms
2
...
Catabolic (catabolism)
That part of metabolism involved in breaking down larger molecules to smaller ones
...
On balance, catabolic
reactions are normally exothermic
...
Anabolic
Those reactions that require energy (synthesis of glucose, fats or DNA) are called
anabolic reactions or anabolism
...
g
...
Amphibolic
These do abit of both!
A common metabolic currency transaction
ATP (adenosine triphosphate) is paramount (over NAD+ and FAD)
Part of free energy derived from oxidation of foodstuffs (catabolism) is transformed into this
highly accessible molecule
...
g
...

This is a preparation stage – so no useful energy is captured
...
Most are converted into acetyl CoA
...
Then, a proton gradient is generated as electrons flow from the
reduced forms of these carriers to O2: THIS GRADIENT IS USED TO SYNTHESISE ATP
...

• Versatile – couple thermodynamically unfavourable reactions to favourable ones
...
Proton gradients
can drive ATP synthesis when protons flow through an ATP synthesising enzyme (i
...

in mitochondrial membranes)
...
Some of this can be “harnessed” in the form of ATP to do so biological
work, e
...
biosynthesis, ion transport, muscle etc
...
g
...
if
catabolic pathways are oxidative, anabolic pathways must be reductive, and require
a source of reducing power
...

c) Production of intermediated – that may be precursors of other biosynthetic (anabolic)
processes
...
In which a 6-carbon glucose
molecule is split into 3-carbon molecules
...

In summary, one molecule of glucose is converted to TWO molecules of pyruvate,
aerobically, the pyruvate can be decarboxylated (mitochondrial matrix) to produce AcetylCoA
...

Anaerobically, pyruvate can be further processed to lactate or ethanol
...

o 2 mols of ATP are consumed for each mol of glucose
o Glucose is converted to fructose-1,6-bisphosphate
...

• In stage 2 fructose-1,6-bisphosphate is cleaved into 2 3-carbon units of
glycerladehyde-3-phosphate
...
4 mols of ATP and 2 mols of NADH are gained from
each initial mol of glucose
...

1
...

2
...


Isomerisation: A
...
Fructose 6-phosphate (F-6-P)
a
...
If in an open-chain form of fructose =
C2, it’s a keto group
...
Therefore PGI opens the ring
of glucose, catalyses the isomerisation, and
then promotes the formation of the 5membered ring of F-6-P
...

Stage 2: à à à à

Stage 3:
After the second stage comes the krebs
cycle:

!
Remembering the krebs cycle points:
o Pyruvate
o Acetyl CoA
o Citrate
o Isocitrate
o Α-ketoglutarate
o Succincyl CoA
o Succinate
o Fumarate
o Malate
o Oxaloacetate

Metabolism of Triglycerides:
1
...
Fatty acids are building blocks of phospholipids and glycolipids
3
...
Fatty acid derivatives serve as hormones and intracellular messengers
...
75 times as much energy as 1g of hydrated glycogen
Complete oxidation of fatty acids is ~38kJ g-1
Oxidation of carbohydrates and proteins is ~17kJ g-1
Adipose cells:
These are specialised as a site of triacylglycerol synthesis and storage
...

Adipose cells can be transported to tissues by their blood
...

An example of energy stores at their most needed and efficient requirements are that of
migration
...

This occurs primarily in the duodenum during digestion and liberates fatty acids from
Adipose cells
...

Unlike carbohydrates and proteins, lipids present a special problem:
These molecules are not soluble in water
Therefore: how are they made accessible to hydrophilic lipases?
Dietary triacylglycerol’s are emulsified by bile salts (i
...
cholic acid, glycholate and
taurocholic acid) in the intestinal lumen
...

Finally, digestion products are carried in micelles to the intestinal epithelium for transport
across the plasma membrane
...
e
...

Dietary lipid transport:
Once in the intestinal mucosal cells, the triacylglycerol’s are re-synthesised from fatty acids
and monoacylglycerol’s and packed into chylomicrons (lipoprotein transport particles)
...

Released into the lymph system à blood
Chylomicron:

!
There are 3 stages in the utilisation of fatty acids as fuels:
1
...
Activated and transportation
3
...

Hormonally controlled lipases and phosphorylation of 2 key proteins:
• Perilipin A, a fat droplet-associated protein
...
This phosphorylated lipase hydrolyses triacylglyceride’s
to free fatty acids
...

Fatty acids are oxidised in the mitochondria
...
They are first activated through the formation of a thioester linkage to coenzyme A
before mitochondrial entry
...
How do they get there?
• Fatty acids are conjugated to carnitine for transport across the inner mitochondrial
membrane into the matrix
...

iii
...


This reaction is catalysed by carnitine acetransferase I, which is bound to the outer
mitochondrial membrane
...


Breakdown to Acetyl CoA:
1
...
Fatty acid chain is shortened by 2 C’s
FADH2, NADH and Acetyl CoA are generated
i
...
Oxidation takes place at the β-carbon of the fatty acid
...

iii
...
e
...

i
...

iii
...


Β-oxidation accomplishes the complete degradation of saturated fatty acids having an even
number of carbon atoms
...
However additional steps are required for unsaturated
and unevenly C-numbered fatty acids
...

The additional steps are 2 only and require the enzymes of: an isomerase and a reductase
...

• The citric acid cycle is the final common pathway for the oxidation of fuel molecules
(carbohydrates, fatty acids and amino acids)
• Most enter the cycle as acetyl coenzyme A (acetyl CoA)

!

One turn of the citric acid cycle produces:
• 4 molecules of reduced cofactor (3 NADH2 and 1 FADH2)
• 1 molecule “high energy” phosphate (1 guanosine diphosphate (GDP), and ATP
equivalent)

•

2 carbon atoms (as CO2) (NOTE the input was from 2C’s from the acetyl)

Energy powerhouse:
• Acetyl CoA is generated from the oxidative decarboxylation of pyruvate
• Under aerobic conditions, the reactions of this process, citric acid cycle, take place in
the mitochondria of eukaryotes
...

Step 1:
The reaction if catalysed by citrate synthase
Step 2:
The reaction is catalysed by aconitase
Step 3:
The oxidative decarboxylation of isocitrate is catalysed by isocitrate dehydrogenase
...

This oxidation generates the first high transfer potential electron carrier, NADH, in the cycle
Step 4:
A further decarboxylation generates succinyl CoA from α-ketoglutarate, catalysed by αketoglutarate dehydrogenase complex
...

Step 6 and 7:
The final stages of the cycle are reactions of 4C compounds and constitute the final stages
of the citric acid cycle: regeneration and oxidation
...
Malate is oxidised to
form oxaloacetate, catalysed by malate dehydrogenase
...
5O2 à 3CO2 + 2H2O
C=3 H=4 O=8

C=3 H=4 O=8

Can we account for the items in this equation?
• First CO2
o There are 3 decarboxylation reactions (pyruvate, isocitrate, α-ketoglutarate)
therefore CO2 balances
...
5 molecules of O2 represent five atoms of oxygen there are 5 oxidation
steps:
▪ Oxidative decarboxylation of pyruvate (NAD+)

▪
▪
▪
▪

•

Oxidation of isocitrate (NAD+)
Oxidation of α-ketoglutarate (NAD+)
Oxidation of succinate (FAD)
Oxidation of malate (NAD+)

Third H2O
o The equation predicts that 2 molecules of water are produced
o However the 5 atoms of oxygen will generate 5 molecules of water when
oxidising the 5 reduced co-factors
...

1
...
This yields a great deal of energy: 3ATP produced per molecule of
NADH, 2 per FADH2 and 2 per GTP
...

Together with the 4 ATP (gross) produced in glycolysis, this adds up to 32 molecules
...
Generation of reduced cofactors
The cycle yields 3 NADH and 1 FADH2 per turn of the cycle, i
...
8 per molecule of
glucose, this is potentially available for biosynthetic purposes
...
Provision of metabolic intermediates
There are several intermediates in the citric acid cycle that are potentially useful to
“tap-off” as precursors for other processes
...
g
...

Succinyl-CoA is the starting point in the biosynthesis of porphyrins
...

It takes place in the mitochondria and is the major source of ATP in aerobic organisms
...
To provide this much
energy requires 83kg of ATP
...

The solution? = recycling ADP back into ATP
Each ATP molecule is recycled approx
...


Out and in of the matrix:
•
•
•
•

A flow of electrons from NADH and FADH2 to O2
This takes place through protein complexes in the mitochondrial inner membrane
and leads to the pumping of electrons out of the mitochondrial matrix
...

ATP synthesis is generated when protons flow back into the matric through an
enzyme complex

From electrons to protons:
In the citric acid cycle, carbon fuels are oxidised to yield electrons with high transfer
potential
...

Phosphoryl-transfer
The final stage of oxidative phosphorylation is carried out by ATP synthase
...

Pentose Phosphate Pathway:
The PPP generates NADPH from the oxidation of glucose
Nicotamine adenine dinucleotide phosphate (NADPH) is the currency of readily available
reducing power in cells
...

This pentose pathway can also be used for the catabolism of pentose sugars from the diet
and the synthesis of pentose sugars for nucleotide biosynthesis
...


The pentose phosphate pathway has 2 important products that are of great importance in
specific tissues:
1
...
these
molecules are required by rapidly growing cells such as those in bone marrow, skin
and intestinal mucosa
...
The other major product is the reducing power of NADPH which is required for
reductive biosynthetic reactions and contributes to the protection off tissues from
damage due to reactive oxygen species
...


The pentose phosphate pathway is logically divided into 2 components:
• An oxidative generation of NADPH
• The second portion of pentose pathway is non-oxidative phase
...

Glucose 6-phosphate + 2NADP+ + H2O
A dehydrogenation of glucose 6-phosphate at C1 starts the pentose phosphate pathway
...
An enzyme highly
specific for NADP+
Non oxidative phase:
This phase is characterised by the catalytic inter-conversion of 3,4,5,6 and 7-carbon sugars
in a series of non-oxidative reactions
...

Ribose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate
by:
• Transketolase
• Transaldolase
These enzymes create a reversible link between the PPP and glycolysis by catalysing the
following 3 reactions:
FIRST
C5 + C5 transketolase C3 + C7
SECOND C3 + C7 transaldolase C6 + C4
THIRD
C3 + C7 transketolase C6 + C4
First of these three reactions (FIRST) link the PPP with glycolysis: formation of
glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate from two pentoses
...

We can conclude this by saying:
Excess ribose 5-phosphate formed by the PPP can be completely converted into glycolysis
intermediates
...

Glucose 6-phosphate is metabolised via both pathways
...
Dehydrogenation of glucose 6-phosphate
The first reaction in the oxidative step, and is essentially irreversible
...
Low levels of NADP+ inhibit
Dehydrogenation of glucose 6-phosphate because its required as the electron
acceptor
...
This inhibitory effect is intensified by
The fact that the NADPH competes with NADP+ in binding to the enxyme (Glucose 6phosphate dehydrogenase)
4
...

Glucose 6-phosphate and protection against stress:
1
...

2
...

3
...

4
...
This is accomplished by the reducing power supplied by NADPH
...
Drug induce haemolytic anemia
2
...
Cells with reduced levels of glucose 6-phosphate dehydrogenase are especially
sensitive to oxidative stress because less NADPH is present to regenerate
glutathione (GSH)
4
...




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