Brain requires glucose all the time. Muscle can last on fatty acids very well. RBCs rely on
Type 2: Insulin Resistance
Type 1: Autoimmune disease, body attacks insulin releasing cells.
- Storage of energy as fat is very efficient. Much higher energy in fat. Carbohydrates
require lots of water weight in order to store.
- Small ATP free in the body. Lots of ATP is turned over though.
- the sum of biochemicalprocesses involved in the synthesis, breakdown, and inter-
conversion of constituents in cells and organisms
- is where anabolism and catabolism intersect, often sharing pathways and metabolites.
- Because the pathways of intermediary metabolism are essential for life, they are tightly
regulated through a variety of mechanisms.
Gene sequencing and Genome databases
DNA microarrays: mRNA expression levels and microRNAs
- To simultaneouslyassess expression levels of thousands of genes.
- To assess the origins and developmentof disease, the subtypes of disease; disease prognosis
(e.g., in cancer); treatmentoutcomes
- To clarify the specificity of pharmaceuticals
Many systemsbiology approaches for data analysis. Cluster-type approaches assess levels of
transcripts, proteins or metabolitesin relation to known pathways and biological functions.
Proteomics:protein expression levels, and post-translational modifications
- expression levels and characteristics of proteins
- Proteomicapproaches allow investigation into responses of a biological system to different
stimuli, e,g, disease states, or following drug treatment
- Recent progress in analytical techniques for the study of proteins has led to significant
improvementsin the ability to identify peptides and their posttranslational modificationson a
high throughput basis
One gene one protein hypothesis is wrong
Ghrelin/Obestatin do different things but made from one gene
Ghrelin signals you are hungry, obestatin signals you are full
Metabolomics: comprehensiveanalyses of metabolitelevels Metabolomics: comprehensiveanalyses of metabolitelevels
- A new investigativefield that applies advanced analytical techniques to study metabolite
profiles in serum or tissue samples.
- Several hundreds of metabolitessimultaneously!
- By comparing metabolite levels in sequential samples and inferring metaboliteflux,
metabolomicscan also identify rate-controlling steps e.g., that could be targeted for the
developmentof new drugs. Lecture 2
Cell-Cell communication & Compartmentalization
Procaryote unicellular organism; cells lack membrane bound nuclei;
Eukaryote cell or organism having membrane-bound,structurally discrete nucleus other
well-developedsubcellular compartments. Includes all organisms except viruses, bacteria,
- Integral membrane proteins called connexin
- Regulate passage of ions between two adjacent cells
The committingstep catalyzes a reaction that has a large free energy change (irreversible step)
The other enzyme reactions are characterized by a relatively lower free energy change
Oxidation of glucose: small number of relatively complex/orderedmoleculesto a larger
number of simpler molecules(increased entropy)
Energy released !
Creating order has a cost but that order has potential energy
Potential energy from one reaction can be used to drive another one
Role of ATP:
The chemical intermediate linking energy-releasingcatabolic (exergonic) reactions with
energy demanding anabolic (endergonic) reactions
Controls occur at the beginning of a pathway
Inhibition and Allostery
- Non-reactant molecule that resembles the substrate interferes with access of the normal
substrate to the substrate binding pocket
- Endogenous inhibitor is feedback inhibitor or negative effector,exogenous inhibitors are
- Binding of a ligand at one site affects binding of another at another site
- Structural alterations interfere with the accessibility of other ligands, substrates or cofactors,
or may disturb the catalytic site.
Allosteric enzymesexist in at least two different states (controlledby the regulatory substances):
R state (R= relaxed): high affinity for substrate
T state (T = tense): low or no affinity for substrate
- Allosteric activatorsand inhibitors induce conversionfrom the T to the R state, and the R to
the T state, respectively.
- Example of this is fructose 1,6-bisphosphate which inactivates glycerol kinase into its
tetramericform when there is sufficient glucose present
Control by post-translational modifications
Transcriptionalcontrol: controlling level of mRNA expression e.g., PPARs and their PPREs
Translational control: at initiation, elongation and termination steps in conversionof mRNA to
To modulate the activities of enzymes already synthesized
For acute control of enzyme activities (milli-seconds to minutes)
- Turn active site on or off
Control By enzyme turnover Control By enzyme turnover
- Ubiquitin pathway important for control of enzyme turnover
- Moleculeswith the PEST motif survive for only about 2-3 mins
- Proteins lacking PEST motif have a half life of about 10 hours