Membrane flow and membrane biogenesis
- Where are membrane lipids incorporated into membranes?
- Where are membrane proteins synthesized?
- What happens to them in the ER lumen?
- What happens to them in the golgi apparatus?
- Note the relationships to inside of organelles to the cell exterior.
- How do proteins get into membranes?
- How do they get from organelle to organelle?
- How to they get incorporated into the plasma membrane?
- What are lipoproteins? What do they do?
Introduction to Metabolism
Overview of Metabolism
Catabolism. Anabolism. Autotroph.
What is thermodynamics? What can it
tell you about a process? Pathway independent.
- G What is G
- G° (definition)
- G° ' (definition)
- G = H-
- What does it indicate about energy availability?
- What does G tell you about a
- G = G°
'+ RT lnQ.
- G° ' = -RT lnKeq.
- Know how to solve simple problems using thermo relationships.
- How do you find G for a series
of reactions? Keq?
- Driving reactions by coupling:
- in parallel. (Note special function of enzymes in this case.)
Metabolic Pathways: sequences of consecutive enzyme catalysed reactions which are readily studied and traced.
- Pathways are thermodynamically favored.
- Note that individual reactions may be favorable or unfavorable.
- Some reactions are sequentially coupled to create favorable process.
- Some reactions are coupled in parallel to create favorable process.
- Parallel coupling has advantage of using a common intermediate (e.g. ATP, NADH) and reducing overall complexity of process.
- Pathways often are "inefficient" in sense that much energy is "thrown away" as heat.
- Necessary to assure completion of pathway process and enable effectiveness.
- Pathways are regulated by enzymes catalyzing reactions which:
- highly favor the products, and
- are held far from equilibrium in the cell.
Characteristics of pathways:
- First committed step (flux generating step)
- Localized in eukaryotes
- Catabolic and anabolic pathways are generally distinguished by coenzymes and/or compartmentalization.
- Hydrolysis of polymers to monomers.
- Monomers metabolized to Pyruvate and/or Acetyl CoA (some amino acids go to/via Kreb's Cycle intermediates).
- Acetyl CoA is oxidized to carbon dioxide and reducing equivalents (NADH and FADH2).
- Reducing equivalents are oxidized with molecular oxygen to water with the capture of energy as ATP (takes place in Mitochondria in eukaryotes).
Energy capture in catabolism: ATP is the common energy "currency" of metabolism.
- Why ATP?
- Phosphoric acid anhydride bond is unstable to hydrolysis (thermodynamically unstable)
- However, Phosphoric acid anhydride bond is not readily hydrolyzed (kinetically stable)
- Shifting Equilibria (deltaG) with ATP.
- "Hi Energy".
- What do we mean by "hi energy?" (The compound has a large negative deltaG° ' of hydrolysis)
- High free energy defined as equal to or greater than the energy of hydrolysis of ATP to ADP.
- Low free energy defined as less than the energy of hydrolysis to ATP to ADP.
- NAD(P)+ and Flavins as "universal" carriers for electrons.
- Note chemically active vs. recognition portions of these molecules.
3 stages :
Stage I - preparatory (Glu F-1,6-bisP)
- Energy is invested.
- "Semi-symmetrical" molecule is formed, which can
be cleaved into two three carbon-one phosphate trioses in next
Stage II - oxidative phosphorylation (F-1,6-bisP 2 x 3-PGA)
- Triose phosphates formed by cleavage reaction, then isomerized
to single aldotriose phosphate.
- Aldotriose is oxidized using NAD+ to create a
high energy phosphoric-carboxylic mixed acid anhydride.
- High energy phosphate is transferred from mixed acid anhydride
to ADP to give ATP (2x) and a low energy phosphoglycerate.
Stage III - energy generation (2 x 3-PGA 2 x Pyr)
- Primary phosphate ester in 3-PGA is isomerised to a secondary ester (2-PGA).
- Low energy secondary ester is dehydrated (alcohol elimination) to create a high energy enol phosphate.
- High energy phosphate is transferred from enol
to ADP to give ATP (2x) and and an enol.
- The enol tautomerizes spontaneously to Pyruvate, removing the enol product of the previous reaction and driving it forward.
Need to regenerate NAD+
©R A Paselk
Last modified 16 March 2011