Chapter 13: Overview of Metabolism - PowerPoint

I. Thermodynamics of Phosphate Compounds

A. Life Requires energy to Drive Endergonic Chemical Reactions

1. Biosynthetic reactions which produce proteins, nucleic acids, and carbohydrates

2. Reactions to maintain concentrations gradients, membrane potentials etc.

3. Energy is provided by oxidation of nutrients, e.g. glucose, by O2, nutrients contain H2, the more H2, the greater the energy to be obtained by oxidation.

4. Energy from oxidations is stored in high energy intermediates, principally ATP
Fig. 13-3

B. Phosphoryl Transfer Reactions

1. Prototype reaction: R1-O-PO3-2 + R2-OH == R1-OH + R2-O-PO3-2

2. This class or reaction is of enormous emportance in Biochemistry

  • energy for biosynthesis of proteins, nucleic acids and carbohydrates
  • energy for active transport--> concentration gradients and membrane potentials

3. The most important involve ATP

C. Other High Energy Compounds

1. Acyl Phosphates: e.g. acetyl phosphate and 1.3-Bisphosphoglycerate

2. Enolphosphates: e.g. phosphoenol pyruvate; enol hydrolysis product is less stable than the keto tautomer giving the reaction extra energy

3. Phosphoguanides: phosphocreatine and phosphoarginine Fig. p367

4. Glucose-6-phosphate or glyceraldehyde-3-phosphate: lower in energy because they do not have high charge densities or resonance stabilization compared to their hydrolysis products.

D. The Role of ATP

1. ATP is intermediate in energy ==> it serves as an energy conduit between high energy and low energy phospho-compounds

2. The highly exergonic phosphoryl transfer reactions of nutrient degradation are coupled to formation of ATP rom ADP + Pi

3. Consumption of ATP

  • early stages of sugar breakdown producing low energy phosphate compounds
  • interconversion of nucleoside triphosphates: ATP + NDP == ADP + NTP
  • physiological processes such as muscle contration and active transport agains concentration gradients
  • additional phosphoanhydride cleavage: ATP ==AMP + PPi followed by PPi == 2PI
    pyrophosphate cleavage provides extra energy for fatty acyl-CoA synthesis and nucleic acid biosynthesis

4. formation of ATP

  • substrate level phosphorylation--diret transfer from a high energy compound
  • oxidative phosphorylation & photosynthesis--involves H+ gradient intermediate
  • adenylate kinase: AMP + ATP == 2 ADP

5. Rate of ATP turnover--ATP is a free energy transmitter not a reservoir

  • ATP pool can supply energy for about 1 minute
  • at rest a human turns over ATP at a rate of approximately 1.5 kg/hour
  • brain cells have only a few sec supply of ATP

6. Phosphocreatine provides a "high energy" reservoir for ATP formation

ATP + creratine == Phosphocreatine + ADP DG = +12.6 kJ/mole

Chapter 14 - Glycolysis

II. The Glycolytic Pathway: Living organisms all metabolize glycose by essentially identical pathways.

A. Overview of Glycolysis

1. phosphorylate glucose

2. convert phosphorylated intermediates to compounds with high phosphate group transfer potential

3. couple hydrolysis of these high energy compounds to ATP synthesis Fig. 14-1

Stage I: Reactions 1-5 involve phosphorylation of a hexose and cleavage to form two molecules of glyceraldehyde-3-phos; this process uses 2 ATP

Stage II: 2 glyceraldehyde-3-phos --> 1 pyruvate + 4 ATP - 2 ATP (used in Stage I) = net production of 2 ATP/hexose

Overall Reaction:
Glucose + 2NAD+ + 2ADP + 2Pi == 2NADH + 2pyruvate + 2ADP + 2H2O + 2H+

4. NAD+ must be regenerated / recycled, it is the primary oxidizing agent in glycolysis

Anaerobic muscle: NADH is reoxidized when reducing Pyruvate ---> Lactate

Anaerobic yeast: Pyruvate decarboxylase ---> Acetaldehyde which NADH reduced to CH3CH2OH + NAD+

Aerobic conditions: mitochondria oxidize NADH --> NAD+ using O2 as an oxidant and producing ATP

B. The Reactions of Glycolysis Fig. 14-1

Stage I

1. Hexokinase: Glucose + ATP --> Glucose-6-Phosphate
glucose causes the active site to close on substrates preventing non productive hydrolysis of ATP by H2O
Fig. p386 & 14-2

2. Phosphoglucose isomerase: Glucose-6-phos == Fructose-6-phos; catalyzed by general acid-base mechanism Fig. 14-3

3. Phosphofructokinase--2nd ATP utilization, similar to hexokinase; this is the rate determining step and a site of regulation of glycolysis

4. Aldolase: FDP == Glyceraldehyde-3-Phos + Dihydroxyacetone phosphate (DHAP)
This is the aldol cleavage of fructose diphosphate producing two three carbon sugar phosphates (Note: if aldolase cleaved glucose it would produce fragments of two different sizes.
Fig. 14-5

5. Triosephosphate Isomerase (TIM): similar to hosphglucose isomerase with an Enediol intermediate; concerte general acid base catalysis. TIM is a perfect enzyme and is diffusion controlled; this means that DHAP and glyceraldehyde-3-Phos are kept in equilibrium.Fig. p391

Stage II

6. Glyceraldehyde-3-phosphate Dehydrogenase: first high energy intermediate formed

Glyceraldehyde-3-Phos + NAD+ + Pi == 1,3, Bisphosphoglycerate + NADH + H+
Fig. 16-14

7. Phosphoglycerate Kinase
1,3-Bisphosphoglycerate + ADP == 2-phosphoglycerate + ATP
Fig. p395

Reactions 6 and 7 are an example of coupled reactions:

endergonic: GAP + Pi + NAD+ == 1,3, BPG + NADH D G°' = +6.7 kJ/mole

exergonic: 1,3,-BPG + ADP == 3 PG + ATP D G°' = -18.8 kJ/mole

GAP + Pi + NAD+ + ADP --->3 PG + NADH + ATP DG°' = 6.7 kJ/mole

8. Phosphoglycerate Mutase Fig. 14-12

9. Enolase--second high energy "intermediate formation Fig. p398

10. Pyruvae kinase -- 2nd ATP Generation-