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Biochemistry
-
Metabolism
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Course Content
Glycolysis
Entry of
fructose
and
galactose
into glycolysis
Fates of
pyruvate
Gluconeogenesis
Cori
cycle
Citric
acid (TCA, Krebs) cycle
Electron
transport and
oxidative
phosphorylation
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Recommended Reading
Berg
JM,
Tymoczko
JL and Stryer L (2012) Biochemistry (7th Edition): WH Freeman
Campbell
MK and Farrel SO (
2007
) Biochemistry (6th Edition) (Thomson Brooks/Cole)
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Metabolic Biochemistry
Energy
is required by all living organisms as many biological processes require
energy
Mechanical
work e.g. Muscle
contraction
Active
transport
Synthesis of complex
biomolecules
from simple
precursors
Signal transduction (environmental responses), generation of
light
(fire flies) and
electricity
(eels)
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Muscle Contraction
Actin
Myosin
ATP
ADP
Ca2+
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Active Transport/Neurotransmission
Na+
Na+
K+
K+
ECF
ICF
ATP
ADP
[Na+ =
150mmol
/l]
[K+ =
110
mmol/l]
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First Law of
Thermodynamics
"For any physical or chemical change, the total amount of
energy
in the universe remains
constant
"
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Energy cannot be created or destroyed, but it can be
converted
from one form to another
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Sources of energy for living organisms
Heterotrophy
– Energy and volume are obtained from other organisms e.g. mammals
Autotrophy
– Energy derived from sunlight and volume for CO2 in the atmosphere e.g. plants
Chemotrophs
– Energy from chemical redox reactions
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Chemoorganotrophs
Extract energy from organic compounds by
oxidation
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Energy content of different macromolecules
Fats
-
9
kcal/g
Carbohydrates
-
4
kcal/g
Proteins
-
4
kcal/g
Alcohol
-
7
kcal/g
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Glucose oxidation
Glucose
+ 6O2 -> 6CO2 +
6H2O
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Healthy human diet
Appropriate balance between
carbohydrate
,
protein
and fats
Energy
intake and
energy
use also need to be balanced
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Diets in developed countries are sometimes too high in
fat
or in
processed carbohydrate
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Fat
contains more calories per gram than other foods and overconsumption can lead to
obesity
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Diets high in
saturated lipids
or cholesterol also increase the risk of developing
heart disease
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Diets high in processed carbohydrate may increase the risk of developing
insulin resistance
and
type 2 diabetes
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Obesity
increases the risk of both
heart disease
and diabetes
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Functions of Metabolism
Synthesis
of precursors e.g. amino acids, Fatty acids, carbohydrates, proteins nucleic acids
Provision
of
energy
for synthesis, mechanical work, heat production, ion pumps etc.
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Types of metabolic pathways
Linear
Divergent
Convergent
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Metabolism
Hundreds of different
enzyme-catalysed
reactions
Central metabolic
pathways are few in number and highly
conserved
throughout nature
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If energy released during breakdown of fuel molecules was simply released as
heat
then cells and the body would be
destroyed
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ATP
Energy
rich molecule with high
phosphoryl
transfer potential
Contains
2
phosphoanhydride bonds on its
triphosphate
unit
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ATP hydrolysis
1. ATP +
H2O
-> ADP + Pi +
energy
2. ATP +
H2O
-> AMP + PPi +
energy
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ATP hydrolysis
Free energy (ΔG) is
negative
so
thermodynamically unstable
However kinetically stable (in absence of a
catalyst
, breakdown is very
slow
)
For ATP hydrolysis ΔG =
-7.3
kcal mol-1 or
-10.9
kcal mol-1
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A human hydrolyses about
55kg
of ATP in
24
hours
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Total body ATP is only
50g
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Turnover of ATP is very
high
- In a sprinter average lifespan of 1 ATP molecule is
1.5
sec
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O2
is needed to synthesise ATP efficiently so about
10,000
litres of air needs to be breathed each day
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Substrate level
phosphorylation
Transfer of phosphoryl group from metabolites with high-phosphoryl transfer potential to
ADP
producing
ATP
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Oxidative phosphorylation
Process of
ATP
formation as a result of transfer of electrons from fuels via electron carriers (NADH or FADH2) to the
final electron acceptor oxygen
In animals over 90% of
ATP
formed by this method, carried out in the
mitochondria
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Creatine
20g/day creatine – probably
increases
creatine
phosphate
concentration in muscle
Normal source of creatine is 1g/day from diet, synthesised in liver from glycine,
arginine
and
methionine
Total body pool approx 120g, spontaneously
degrades
to creatinine which is excreted in
urine
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Hexokinase
Kinase –
phosphorylating
enzyme
Hexo –
six
carbon sugar
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Formation of glucose 6-phosphate
Glucose 6-phosphate
is "trapped" in the cell because of its
negative
charge
The phosphoryl group begins to
destabilise
glucose and facilitate further
metabolism
Equilibrium of
reaction
strongly favours
glucose 6-phospate
(effectively irreversible reaction)
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Phosphoglucose isomerase
Isomerase – convert from one isomer (
glucose
) to another (
fructose
)
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Phosphofructokinase
Kinase
– phosphorlyating enzyme
Phosphofructo – fructose with a
phosphoryl
group attached
Key regulatory
enzyme in
glycoloysis
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Aldolase
Named from the reverse reaction which is an
aldol condensation
6
carbon sugar split into
two 3
carbon sugars
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Triose phosphate isomerase
Isomerase
– convert from one isomer (dihydroxyacetone phosphate) to another (glyceraldehyde phophate)
GAP
is used directly in glycolysis whereas DHAP is not
Isomerase converts
DHAP
(ketose) to
GAP
(aldose) for use in glycoloysis
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Glucose has been converted to
glyceraldehyde 3-phosphate
but no
ATP
has been synthesised
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Glyceraldehyde 3-phosphate
dehydrogenase
Dehydrogenase
– transfer "high energy" electrons from complex organic molecule to NAD+ to form
NADH
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