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Saturday, January 16, 2010

Enzymes

I have started to discuss my theory with Gary Taubes and this blog post is intended to go into a bit more detail about how stuff works. Trying to explain the following over the phone with hand-waving is likely to be very difficult, especially when I forget things!

Firstly, see Enzyme. Their name always ends in "ase". The thing about enzymes is that their activity can be increased & decreased by the level of substrate i.e. how much "stuff" there is going in to the reaction and how much "stuff" there is coming out of the reaction. Activation & inhibition can also be produced by other substances not directly involved in the reaction.

To get from Glucose (assuming muscle cells) to Pyruvate involves a multi-step process involving lots of different enzymes and other substances. Here's the first step.

Glucose + 1 molecule of ATP (Adenosine Tri-Phosphate) is converted by Glucokinase (with the aid of 2 Magnesium ions) into Glucose-6-phosphate + 1 molecule of ADP (Adenosine Di-Phosphate) + 1 Hydrogen ion. Here's the last step.

Phosphoenolpyruvate + 1 molecule of ADP is converted by Pyruvate kinase (with the aid of 2 Magnesium ions and 1 Potassium ion) into 1 molecule of Pyruvate + 1 molecule of ATP.

As stated in Everyone is Different , muscle cells at rest derive most of their energy from fat (Tri-Palmitin). Inside the cell mitochondria, molecules of Palmitoyl CoA (from Palmitate from hydrolysed Tri-Palmitin) produce energy starting with a process called beta-oxidation, where Acetyl CoA is repeatedly "snipped-off" yielding a fatty acid that's shorter by 2 carbon groups, 1 molecule of Acetyl CoA, 1 molecule of FADH2 + 1 molecule of NADH+H+ (don't ask!) until all that's left is Acetyl CoA. The molecules of Acetyl CoA enter the Krebs Cycle which produces more energy.

As muscle cells at rest derive most of their energy from Acetyl CoA rather than Pyruvate, Pyruvate accumulates. This inhibits the enzyme Pyruvate kinase causing an accumulation of Phosphoenolpyruvate. This inhibits the enzyme that produces Phosphoenolpyruvate etc etc. This results in an accumulation of Glucose-6-phosphate. This inhibits the enzyme Glucokinase causing an accumulation of Glucose. This inhibits the Glu-T4 transporters making muscle cells temporarily insulin resistant. Blood glucose stops entering muscle cells.

Things change when muscle cells undergoing anaerobic exercise use Pyruvate instead of Acetyl CoA. A lack of Pyruvate activates the enzyme Pyruvate kinase causing a lack of Phosphoenolpyruvate. This activates the enzyme that produces Phosphoenolpyruvate etc etc. This results in a lack of Glucose-6-phosphate. This activates the enzyme Glucokinase causing an lack of Glucose. This activates the Glu-T4 transporters making muscle cells temporarily insulin sensitive. Blood glucose enters muscle cells even if blood insulin level is normal.

The same principle applies to fat cells regarding glycerol-3-phosphate. In conclusion:
Within cells, the biochemical processes that produce "stuff" are not static but vary according to the needs of the cells.

I need a break!

While waiting to get hold of Taube's book Good Calories Bad Calories, I'm reading Toban Wiebe's Complete Notes to Good Calories, Bad Calories by Gary Taubes.

I'm also reading Anthony Colpo's latest articles on http://www.anthonycolpo.com/ . This guy doesn't mince his words!

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