Transport and rate phenomena in biological systems
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Transport and Rate Phenomena in Biological Systems. Redux. Molecules. They can only do two things: They react They move They are the most important elements in biological systems. Atoms acquire meaning only in molecules.

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Molecules
Molecules

  • They can only do two things:

    • They react

    • They move

  • They are the most important elements in biological systems.

    • Atoms acquire meaning only in molecules.

    • All larger-scale entities acquire their ultimate meaning and explanation in molecules.


Molecules deliver
Molecules deliver:

  • Messages

  • Material – mass, energy

    Molecular delivery is particularized by packaging what is to be delivered (message or material) so that only intended recipients are reached. Compare with path-particularized systems.


Molecular motion
Molecular Motion

  • Convection

  • Diffusion

  • Convective diffusion

  • Compartments


Compartment representations
Compartment Representations

  • Input and output via convection, permeation – passive, permease-driven, active and coupled transport

  • Accumulation with and without volume change

  • Reaction: equilibrium, power-law, enzymatic.


Reaction
Reaction

  • A few reactions among many are rate limiting. Others equilibrate either with reactants or products of rate-limiting processes.

  • In processes involving both reaction and transport, rate-limiting step may be of either type.


Enzyme reactions
Enzyme reactions

  • Linear in enzyme concentration.

  • Regulatible ('allosteric effectors')

  • Substrate dependencies:

    • First-order at low concentration

    • Zero-order at high concentration

  • Enzyme reactions are usually irreversible.

  • Enzymes are catalysts – they never change an equilibrium– only the rate.


Permeases
Permeases

  • Can be regarded as enzymes that facilitate transport rather than reactions.

  • Unlike enzymes, permeases do show reversible behavior.

  • Models exist for both facilitated (not active) and active transport.


Ionic equilibria and membranes
Ionic equilibria and membranes

  • Not considered in these lectures.

  • May be important – especially in neural cells.


Cooperativity
Cooperativity

  • Desirable biological function that supports homeostasis.

  • Generated by multiple mechanisms.

  • Expressed in terms of "Hill Functions":


Steady state
Steady State

  • All variables of interest have the same value at all moments of observation

  • Steady state is a property of the system and the frame of reference.

  • Steady state means, at the most fundamental level, no change in accumulation.

  • Cyclic and "practical" steady states.


Cells
Cells

  • A cell

  • Cohorts of cells

    • normally asynchronous

    • synchronization

    • cyclic and sequential behavior is concealed in cohort-scale measurements.


When is a cell not one compartment
When is a cell not one compartment?

  • When it is a nerve cell

  • When its "organelles" must be considered:

    • Nucleus

    • Mitochondria

    • Processing elements

  • When related chemical species are considered: finite-rate chemical transformations define compartments, too.


Macroscopic problems cell aggregates organs
Macroscopic Problems: Cell Aggregates, Organs

  • All basic representations are useful if properly reinterpreted:

    • What goes in, plus what is made, minus what goes out, is always what accumulates. But one must measure what is defined, or define what is measured!

    • The art (kunst) that must be added to the science (wissenschaft) of macroscopic analysis is picking the right compartments and the right "entities" to follow.


Genomics
Genomics

  • The concept of the genome and the cells.

  • Regulation of homeostasis

  • Control of Development

    • Reversibility of the normally unidirectional development pathway.


The goodwin equations
The Goodwin Equations

  • Gene transcription

  • mRNA translation

  • Product synthesis.

  • Feedback to the genome.


Gene transcription
Gene transcription

  • one or two genes are transcribed to mRNA by RNAP's controlled by transcription factors.

    • (Constituitive genes)

    • Inducing and repressing transcription factors

    • Attenuation

    • "Cross-talk" among genes.


Mrna translation
mRNA translation

  • mRNA's are generated by transcription, destroyed by a first-order reaction, exist at a steady-state level. Normal and abnormal destruction kinetics – apoptosis.

  • Ribosomes copy instructions in mRNA into proteins. Some of these are final products. Many are catalysts (enzymes, permeases, signal molecules) that control the formation of a 'final' product.


Product synthesis
Product Synthesis

  • Some synthesized products are molecules that feed back information to regulate the geneome: transcription factors. Transcription factors are frequently in "apo" form (incomplete, inactive) and must combine with small molecules to become active.

  • All products are candidates for destructive processes that may be 'smart' or 'dumb'.


Goodwin equations as a feedback system
Goodwin Equations as a feedback system

  • Equations thus constitute a genome-cell feedback system.

  • Positive feedback is not seen as destructive in biological systems because of saturation phenomena and developmental requirement.

  • Intercellular feedback – to synchronize clones and inter-relate different cell lines.


Tissue engineering
"Tissue Engineering"

  • "Ultimate*" solutions in the repair of deformed, damaged, or prematurely aged tissue.

    • Redirect the natural system.

    • Timing issues

    • New cells, old cells, transitional states.

* If you are going to predict the future, do it often. J.K. Galbraith


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