Block 1 2 Feb 2017

Subject: Biochemistry
Lecture: The concept of metabolism, the key
molecular players

1 The Concept of Metabolism and Key Molecular Players

Points to Consider
What is metabolism?
Concepts of anabolism and catabolism?
What fules are used to generated in metabolism?
Some key metabolic cells
Inter-organ transport processes
Cellular transport processes (i.e. translocation)
Enzymes what are they and how do they mediate?
Regulators of metabolic enzymes
What is metabolism?
Metabole means to change.
Metabolism allows us to undertake work, to grow and respond to the environment.
There are two main branches to metabolism
* Anabolism: we use ATP and NADH, because were making things

intermediates + toxins macromolecules + elimination

* Catabolism: breaking things down, we get ATP and NADH

diet + H2 O + O2 + fuels CO2 + intermediates

Key Cells in Overall Metabolism

the liver is involved in the storage, altruism and synthesis.
adipose tissues: the lipid store, and also mobilise tissue when we need it, prolonged activity
kidney:helps to eliminate stuff, it metabolises things as well.
* The kidney and the liver detoxify
muscle: glycogen store, high user of energy
brain: lazy, self-centred
GI tract: absorption, metabolism
glands: hormone release, regulation
Organelles of Metabolism
Cytoplasm
* Non-oxidative catabolism
* Biosynthetic pathways
* Storage of ycogen
* Storage of TAGs

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 ER & Golgi
* SYnthesis & processing of protein
* Synthesis & processsing of complex lipids (PT modications)
Lysosomes
* Low pH - hydrolytic enzymes
* macromolecule degredation
* hydrolysis of endocytosed material
Peroxisomes
* Specialised oxidation reactions
* Very long chain fatty acid oxidation
* Pertubation of this can lead to terminal conditions.
Mitochondria
* Most of the metabolism occurs here and the cytoplasm
* 90% of ATP synthesis
Inter-organ transport in Metabolism
If youre hydrophyllic you can just swim around in the water.
If youre lipophyllic, you need other thigns to get through.
Albumin
* MW 67kDa
* Buffers pH and provides oncotic pressure
Lipoprotein
* Carrier particle for hydropholic compounds
* Varied sizes and densities
* Central core is made up of cholesterol esters and triglycerols
Cellular Transport in Metabolism
We need transport systems to get them in.
Glucose and the GLUT and the SGLT family. These ahave very different properties and deds on
what tissues youre looking as to their specifc role in glucose transport. YOull see how important
the different properties of these transporters are.
Amino acids: protein. Theyve got very specic transporters around.
There are so many different transport systems. Fatty acids getting into your mitochondria; a very
convoluted litte transport system.
Why have they done this? Why are there so many transporters?
By having transporter mediated phenomena, it allows you to control and to regulate biochemical
pathways. Were going to learn about a lot of pathways. He wants to see whether we understands
the pathway by seeing how its regulated. This revovles on our understanding of transport proteins.
What are Enzymes?
Lower the activation energy
How do enzymes facilitate catalysis?
1. Acid-base provision
acidic and basic amino acid groups are ground in active sites
useful in catlysis sin ce they readily donate or accept protons

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 2. Promote Transition State formation
amino acids in the active site stabilise the dsitribtion of electric charge in transition states
the stabilisation reduces the free energy barrier
3. Proximity
catalysis may be accelerated by holding reactants together at an appropriate oreintation
4. Manipulation via protein structural exibility
conformation changes often accompany substrate formation
Components of Enzymes
Active site:
* amino acid side-chains involved in the interaction with substrate
* Binding site: where the substrate is linked by a variety of non-convalent bonds to the protein
* Catalytic region
Regulators of Metabolism
Our body is simply a case of supply and demand.
Cells will store if there is over-supply
Cells will scavenge if fuels are scarce (e.g. protein breakdown)
Weve got all these enzymes that can do all sorts of stuff. But we have to control it somehow. We
cant keep burning glucose to give it energy. SOmehow we need to regulate.
We control it by selectively supplying the cells with what they need because they cant decide what
to take.
The proportions of ATP/ADP and NAD/NADH will determine what it does
Brain, liver, kidney and glands will control things
Hormones provide long-distance effects
ATP
NAD/NADH
Insulin
These will control whether a particular pathway is on or off. It will determine which pathway to
take.
How do they regulate metabolism?
1. Cell REDOX Molecules
How does ADP tell an enzyme slow down?
We saw PFK-1 earlier. When a cell has low [ATP] it means it has high [ADP] as the two are
in ratio. Low ATP, low energy, a pathway has to re up. Under those conditions, a little bit of
substrate, it operates at a very high rate.
WHen weve got high ATP and low ADP, that ADP will oat off the enzyme now and the enzyme
will revert to its sluggish state.
When its starved of energy, it goes boom boom boom, when it has more, it goes very slugglishly.
This is often related to conformational state of the enzyme.
So its a physical interaction.
When your muscle wants to contract, it needs ATP. Thats why weve programmed it such that
its senitive to the level of ATP
2. Hormones
Prolonged response

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 For example a steroid hormone.
Signal Reeptor Second Messenger activates transducers.
The hormone is outside the cell and so we call it a transduction event. Once we re this up,
the hormone can go off and re up another cell.
Effector molecule. An enzyme, for example.
Hormone binds to receptor, second messanger, kinase and thatll give the enzyme a nudge.
That takes a little bit of time.
This can be compared to ATP.

Phosphorylation is a key regulatory strategy of signal transduction

kinase: adds a phosphate
phosphatase: takes off a phosphate
Around 500 kinases and 150 phosphatases in the human genome
They comprise 2% of the genome
Approximately 30% of human proteins are phosphylatable
Kinases and phosphatases are often co-located. PFK-1 (RHS is a kinase, LHS is a phosphatates).
Phosphorylation brings a highly negatively charged moiety to a site
Major conformational changes accompany phosphorylation
In Summary
Metabolic pathways convert cellular compounds
Catabolism is the reakdown of macromolecules
Anabolism is the synthesis of macromolecules
Cells vary in their matbolic capabilites and roles
Organelles provide specialised metabolic roles
Transporters shuttle and sequester metabolites
Enzymes Catalyse biochemical reactions
Cell redox state regulares enzymes activity
Hormones regulate enzyme capacity
Hormones elicit signal tranductio pathways
Phosphorylation is a key regulator strategy