1 metabolism
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to Level 1 BiochemistryDr Brian Green
School of Biological Sciences
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Recommended text
McKee & McKeeBiochemistry
Chapters: 1 & 16
Ch 16 available through QoL
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Control and integration of metabolism
Lectures:
1. Basic principles and regulators of
metabolism2. Hormones and the Endocrine System
3. How can hormone signalling be exploited
in the real world? Insulin and diabetesmellitus
4. The Nervous System
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Basic principles of metabolism
What is metabolism?
Biochemical pathways & how are they
controlled Organs: dividing up the tasks
Hormones controlling metabolism
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Metabolism
The first controlled experiments in human
metabolism were published by Santorio
Santorio in 1614 in his book Ars de statica
medecina that made him famous throughout
Europe. He describes his long series ofexperiments in which he weighed himself in a
chair suspended from a steelyard balance (see
image), before and after eating, sleeping,
working, sex, fasting, drinking and excreting.
He found that by far the greatest part of the
food he took in was lost from the body through
perspiratio insensibilis (insensible
perspiration).
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Whats it all for???
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3 4
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What is metabolism needed for?
1. Acquisition and utilisation of ENERGY
2. SYNTHESIS of molecules needed for cell
structure and function
3. GROWTH and development
4. REMOVAL of waste products
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Integration of Metabolism
Vast number of chemical reactions and
processes occurring simultaneously in cells
and organisms. Cells/organisms have to deliver the right
metabolites, in the right place, at the right
amounts, at the right time..... ....and at the minimum cost in energetic
terms.
10= highly organised complexity
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Factors influencing/regulating metabolism?
Temperature
Enzyme activity
Actions of hormones and other signalling
molecules
Nervous system
Amount of free energy available
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Biochemical pathways
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Metabolic cycle
Reactants/precursors Enzymes End products
Common intermediates Branching point
Metabolites
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Initial substrates for the metabolic pathway
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Reactants/precursors
Enzymes
Catalyse the individual steps in a metabolic
pathway. These enzymes are highlyspecific, the first in a metabolic pathway is
often subject to allosteric control by an end
product.
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Compounds which occur at cross-over or
branching points in metabolic pathways
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Point at which an intermediate may proceed
down one of several alternative pathways,depending on the cells needs. Pathways can
be selected by altering activity of the
enzymes at a branching point.
Common intermediates
Branching point
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Compounds involved in metabolic
pathways; often they are intermediates
between reactants and end products.
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Metabolic hubs which allow the use and re-
use of relatively small numbers of
molecules in the acceptance of products of
one metabolic pathway. E.g. Krebs (TCA)
cycle, urea cycle.
Metabolic Cycles
Metabolites
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+
E
Controlling enzyme activity
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E
Controlling enzyme activity
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+
Compounds fromother pathways+
Substrate+
Activation
-+
TranscriptionTranslocationP.T Modification-egradation
-+
CompartmentalisationOf E & S-
Inhibition
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End-product
-
+
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Negative feedback
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Example:
Excessive amounts of product E build up
E binds to the enzyme X that catalyses the reaction between A &B.
The binding of E changes the shape of the enzyme. This closes the active site of the enzyme.
No more reactions can take place and the pathway is halted.
x
This is allostery process is known as allosteric inhibition.
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Flux through a pathway usually determined
by a rate limiting step.
Rate limiting steps often occur at branchingpoints.
After a branching point a compound usually
has several possible fates.
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Metabolic Regulation
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Metabolic Regulation
- Sequential feedback inhibition
XX XM1 M2 M3 M4
M5
P1
P2
E1 E2 E4
E3
The common steps are inhibited by the product before the branch,
and the first enzyme of each branch is inhibited by the branch
product.
High levels ofP1 and P2 inhibit enzymes E3 and E4,
respectively M3 will accumulate the pathway is
inactivated if both P1 and P2 are high.
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Negative feedbacksystems are the
primary homeostatic mechanisms.
If a desired value, the set point, isdeviated from, compensatory action
begins.
The set zone refers to the range oftolerance in a system.
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Positive feedback
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Example:
Excessive amounts of product E build up
E binds to the enzyme X that catalyses the reaction between A &B.
The binding of E changes the shape of the enzyme. This INCREASES the activity the enzyme.
More reactions can take place and more E and F are produced
x
This is allostery process is known as allosteric stimulation.
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+
P+
INACTIVEACTIVE
Modifications to enzymes can activate/inactivate
e.g. phosphorylation
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Enzyme cascade
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Primary messenger (hormone)
Second messenger
Enzyme 1 (I) Enzyme 1 (A)
E2 (I)
E2 (A)
E5 (I)
E5 (A)E3 (I)
E3 (A)
E4 (I)
E4 (A)
Activates multiple targets
Activates multiple targets
Signal amplification
Catalytic amplification
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Amplified enzyme cascade
Powerful mechanism to amplify and
diversify the action of a hormone.
Uses second messengers such as cyclicAMP to amplify and transduce the message.
In the cascade multiple enzymes are
switched on (activated). Occurs by enzymesundergoing conformational change.
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Metabolism
As nutrient molecules are degraded
(catabolised) into smaller, simpler
molecules ENERGY (ATP) and REDUCINGPOWER (e.g. NADH) are produced
Nutrients are converted
to waste products
such as CO2 and water
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Energy
Energy is defined as the capacity to do work. Living organisms generate most of their energy by
using redox reactions.
In these reactions electrons are often removed or addedas hydrogen atoms (H)
NAD+ (nicotinamide ring shown)
N
C
O
NH2
+ H:-
H
+
R
NADH
N
C
O
NH2
HH
RR = adenine dinucleotide
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Energy
NAD+, FAD+,NADP+ NADH, FADH2,NADPH
The more reduced a molecule (i.e. the more Hatoms it contains) the more energy it contains
Per molecule FAs contain more H atoms thansugars -this is the reason why oxidation of FAsyields more energy than sugars
1g of fat = 9 Kcal : 1g of CHO = 4 Kcal
+ H
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Energy: ATP (p101, McKee)
Hydrolysis of adenosine triposphate (ATP)
immediately and directly provides free
energy for a huge number of biochemicalreactions
e.g. biosynthesis of molecules, active
transport of substances across membranes,mechanical work.
macromolecules
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e.g. digestion e.g. growth, storage, biosynthesis
small molecules
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Metabolism
Anabolicbuilding up (synthesis)
Catabolicbreaking down (degradation)
Amphibolic- involves both anabolic and catabolicprocesses
Organisms must strike a balance between
anabolic and catabolic processes
Hormones are messengers which communicate
most of the information needed to sustain
biological processes
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Metabolism
How does the bodymanage the synthesis
degradation and
interconversion of
biomolecules?
How do all these processes
work in terms of
catabolism and
anabolism?
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Organs
Each human organ performs several roles
and contributes to the bodys overall
function Some heavy consumers of energy to
perform intense tasks (e.g. Muscle, Liver).
Some responsible for supplying energy-richnutrients (e.g. Small intestine, hepatic portal
vein).
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Organs
Using p534-6 in McKee examine:
Small intestine
Liver
Muscle
Adipose tissue
BrainKidney
Give one reason for each being so IMPORTANT
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