Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 438 - Introductory Biochemistry - Spring 2013

Lecture Notes 4:

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Thermodynamics in Metabolism, cont.

Remember that for chemists and biologists the thermodynamic term generally of most interest is the Free Energy for a reaction, that is the energy available to do work.

Since free energy depends on conditions, chemists tabulate free energies under Standard Conditions, (DeltaG°): 298 K, 1 atm., with all concentrations at 1 M.

 K log K DeltaG°' (calories) DeltaG°' (joules)
10-3 -3 4,089 17,100
10-1 -1 1,363 5,700
1 0 0 0
103 3 -4,089 -17,100

For non-equilibrium situations we can find the energy available for work using DeltaG = DeltaG° ' + RT lnQ, where Q is the mass action expression, Q = ([C][D])/([A][B]) for the reaction A + B equilibrium arrows C + D.

One advantage of using free energy is that it is easier to evaluate the overall equilibrium/energy for a series of sequential reactions (its additive instead of multiplicative): DeltaGtot = Sigma [DeltaG]. Often use to predict feasibility of pathways, possible energy yields, and to determine when individual reactions are not at equilibrium (important for determining potential control steps etc.).

Note that the overall free energy determines spontaneity of the reaction - the pathway doesn't matter! As noted above thermodynamics is pathway independent. Thus can drive unfavorable reactions by linking with favorable reactions. This can be done:

    1. Sequentially: sequentially coupled reactions diagram, where the reaction of B to C pulls A to B; or
    2. In parallel: parallel coupled reactions diagram, where the two reactions are linked

Example: glucose + phosphate to G-6-P (DeltaG= +3300 cal) and ATP + water to ADP + Pi (DeltaG= -7600 cal); mix together, no G-6-P (DeltaG= -4300 cal). But link with enzyme, Glu + ATP equilibrium arrows G-6-P + ADP (DeltaG= -4300 cal). All of metabolism depends on such coupled reactions. In essence catabolic reactions drive anabolic reactions etc. via direct, and more commonly, indirect, multi-step, coupling.

Metabolism would be extremely complex if coupled processes directly, however. Instead use an intermediate energy carrier: ATP. Thus catabolic processes make ATP which can then be used for anabolic processes, locomotion, pumping ions across cell membranes (major contribution to basal metabolic rate or BMR), etc. Note that ATP is not used to store energy however. (Often compared to electricity's role in our culture).

FYI – Origin of Life

The oldest fossil evidence for life on Earth dates to about 3.7 by (billion years ago). The Earth itself formed about 4.5 by with the formation of our solar system. It is thought that the Earth was too hot and chaotic to support life until perhaps 3.8 by (intense bombardment of the earth did not end until 3.9 by, thus life arose quite quickly, essentially as soon as possible!

How did this occur? Obviously guess work - no one was there, and there is no record in the rocks that we could even be certain of. However, we have good guesses as to Earth's early environment (atmosphere of H2O, NH3, CO2 and smaller amounts of CH4, NH3, SO2, and H2. If you treat such an atmosphere with any high energy source in the laboratory (as was first done by Miller in 1953) you will get a mixture of organic molecules including many important to organisms today. Interestingly, we also find small precursor molecules all over the Universe - in ancient rocks, meteors, comets etc. Evidence of small precursor molecules (amino acids, nitrogenous bases etc.) also occurs in interstellar space, the atmospheres of carbon stars, gas giant planets etc.

The formation of polymers is more problematic. A major difficulty is that biopolymers are all thermodynamically unstable relative to their hydrolysis products. Some theories, but no certainty as to how polymers may have formed, though polymers have been synthesized under conditions which may have occurred on the early Earth.

The biggest problem for the origin of life is the issue of how we go from polymers to living "systems."

  • Consider the probelm of protein biosynthesis:
    • Going from DNA (information archive) to RNA (usable information) requires a rather complex system to assure accurate transcription today. However, we could assume a much simpler system in the early, low-competition, Earth.
    • Going from RNA to protein incredibly complex:
      • Need adaptor molecules (t-RNA) because there isn't any natural relationship between RNA codes (sequences) and particular amino acids.
      • Need enzymes to match specific amino acids to specific tRNA's because even the tRNA's are not specific to amino acids in term of recognizing them.
        • as a result, need 20 tRNAs + 20 proteins!
      • Need a complex molecular machine, the Ribosome, to read off the mRNA message using the tRNAs and make proteins:
      • Ribosome consists of
        • 1-2 small RNAs + two large, complexly folded, RNAs,
        • 50-100 accesory proteins.
    • The chance of such a system arising spontaneously is truly infinitesimal.
  • "RNA World" has been potulated to solve these dificulties.
    • In this scenario RNA-based life preceeds "modern" life.
    • First "life" combined information and catalytic properties in single RNA-protein molecules.
    • Later there was a transition where proteins took over much of machinery over time.

Pre-Cambrian Life:1

  • 3.8 - microfossils?
  • 3.46 - stomatolites (Australia) [3.5-3.3 microfossils of cyanobacteria?]
  • 2.8 kerogens with low 13C/12C indicative of O2 use by methanogens
  • 2.7-2.5 2-methyl-hopane "fossils" (cyanobacterial markers); steranes (eukaryotic molecular marker, oxygen needed for synthesis)
  • 2.5 -> stromatolite reefs rivaling modern reefs in size and architecture
  • 0.6 Ediacaran fauna
  • 0.54 Phanerozoic begins with deposits of "small shelly fossils" in early Cambrian
    • 0.53-0.52 "Cambrian explosion" – the invention of all or nearly all animal body-plans (basis of animal phyla)

1A slightly enhanced treatment, with photos of specimens at our natural history museum is available by clicking on the link.

Cells and Organelles

Systems Biology

Let's look at a couple of the concepts of systems biology:

1) Robustness

Complex, generalized organisms such as E. coli exhibit an amazing level of redundancy in enzymes etc. For example, of the approximately 4,000 genes in E. Coli less than 300 have been found to be "essential," where essential means the organism cannot grow on rich medium if the gene is deleted. Many genes also appear to be "silent: under more restrictive conditions as well - that is the organism often has more than one pathway to accomplish a given metabolic activity. (Cornish-Bowden & Cárdenas, Nature 14 Nov 2002, p 129)

2) Modularity

We will see that cells are designed at a number of hierarchical levels in a modular fashion, including functional localizations within cells as shown in cell structure.

There are two main cell types: prokaryote and eukaryote.

A typical idealized prokaryote cell is shown in Figure 2.7 on p 39 of Text.

Let's review E. coli for a moment just to recall its size, and also to get an idea of the sizes of various molecules Moodle pics.

prokaryote cell image

public domain image via Wikipedia Creative Commons

Cool facts about E. coli :70% water, 15% protein, 7% nucleic acids, 3% polysaccharides, 3%, lipids, 1% inorganic ions, & 0.2% metabolites.

Complex, generalized organisms such as E. coli exhibit an amazing level of redundancy in enzymes etc. For example, of the approximately 4,000 genes in E. Coli less than 300 have been found to be "essential," where essential means the organism cannot grow on rich medium if the gene is deleted. Many genes also appear to be "silent: under more restrictive conditions as well - that is the organism often has more than one pathway to accomplish a given metabolic activity. (Cornish-Bowden & Cárdenas, Nature 14 Nov 2002, p 129)

Compartmentation in Eukaryotes

As mentioned earlier we will be focusing on eukaryotes in the rest of this course. Eukaryotes differ from prokaryotes in having a nucleus and cell organelles (their cells are physically compartmentalized). As a point of reference, an E. coli cell is about the size of a typical mammalian mitochondria.

Eukaryote cells: anatomy and organelles – Power Point presentation of McKee Chap 2b - Eukaryote Cells.

Let's look at where different major metabolic pathways occur in a "typical" liver cell.

eukaryote cell image

public domain image via Wikipedia Creative Commons

 

Not shown - Glycogen Granules: enzymes of glycogen synthesis and breakdown. including branching and debranching.

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Last modified 30 January 2013