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Glycolysis

CARBS

Glycolysis

  • Occurs in the cytoplasm

  • Doesn’t require oxygen (anaerobic)

  • A series of enzyme-mediated reactions that take glucose (6C) and end up with 2 molecules of 3C pyruvate

  • The first requires energy, the second part produces energy

  • There is a net gain overall as it takes 2ATP to run but 4ATP and the odd NADH at the end

  1. Phosphorylation - requires ATP

    (the enzyme is hexokinase)

Glucose-6-phosphate is not a substrate for glucose transporters so it can’t diffuse out of the cell. This means you can maintain the inward gradient for glucose.

For a muscle/fat cell, the insulin-dependent glucose transporter GLUT4 facilitates the entrance of glucose into the cell (down the gradient)

Hexokinase is one of the regulated enzymes

The enzyme is phosphofructokinase (regulated)

This regulation is inhibited by glucagon and stimulated by insulin

This enzyme also makes fructose-1,6-biphosphate which isn’t stable so it splits into 2 3C compounds (glyceraldehyde-3-phosphate)

This is an energy-generating step. The others are also energy-generating steps following this until:

The enzyme is pyruvate kinase.

The enzymes mentioned are essentially irreversible - the processes only run in one direction.

The Carboxylic Acid Cycle (Krebs)

  • Occurs in mitochondria

  • Not directly dependent on oxygen

An example of a tricarboxylic acid is citrate

  • It converts acetyl CoA into CO2 from pyruvate

The link reaction decarboxylases the pyruvate and adds CoA to the acetate

  • Temporarily, the energy is being stored in reducing NAD+ to NADH by the transfer of electrons

It doesn’t directly use oxygen but in oxidative phosphorylation, NADH is oxidised back to NAD+ which is recycled back into the TCA cycle

  • Acetyl CoA can be made from carbohydrates through glycolysis or from the metabolism of fats/lipids in beta-oxidation. Less obviously, you can do the same with proteins if you break them down into amino acids and deaminate them.

If your carbohydrate metabolism is messed up and you have very low levels of insulin/carbohydrates, you can metabolise ketone bodies (from the metabolism of some amino acids) in the complete absence of glucose.

  • The TCA cycle can take all major food groups through acetyl CoA and make them into energy

It produces the NADh for oxidative phosphorylation

Energy from proteins through deamination.

FATS

Beta Oxidation:

  • Occurs in the mitochondrial matrix

It takes fatty acids and makes acetyl CoA which feeds into the TCA cycle to produce energy.

  • It generates FADH2 and NADH

  • The possibility of generating energy through beta-oxidation before you even feed the acetyl CoA into the TCA cycle

  • This is why fats/fatty acids are such high-density energy stores

e.g. Palmitate completely metabolised can get up to 129 ATP molecules compared to 30 from glucose

Urea Cycle:

  • Amino acids have 1 acidic group and 1 amino group

To metabolise an amino acid you:

  • Deaminate the amino acid

    → Leaving the NH2 in solution becomes NH3 (ammonia) which is water soluble, membrane permeable and extremely toxic

  • Kidney cells make ammonia to regulate body pH

    → Embed the amino group into carbamoylphosphate which enters into the urea cycle

  • Urea is produced which is water soluble and much less toxic

  • Urea then circulates the bloodstream to the kidney which removes the urea from there

Ketogenesis

  • Carried out in the liver

→ An alternative way of making and cu=irculating energy that doesn’t involve glucose

Circumstances where glucose may not be available such as malnutrition and alcoholism (and technically diabetes)

  • Low levels of insulin trigger ketogenesis

Ketogenesis is the process where fatty acids and some ketogenic amino acids are converted into ketone bodies

  • Ketone bodies are beta-hydroxybutyrate, aceto-acetate and the breakdown product acetone

    • They are small water-soluble molecules with the characteristic structure of a ketone

    • They can also be easily converted back to acetone

Ketone bodies circulate and enter any tissue where they can be converted into acetyl CoA which can then support the TCA cycle

Ketogenic diets:

  • High protein, low carbohydrate

  • Can smell them as acetone produced can escape through sweat and breath

Oxidative Phosphorylation

  • Occurs in the mitochondria

  • Creates H2O

  • Makes ATP

  • Where cells get their energy from - the TCA cycle and beta-oxidation have been reducing NAD+ and FAD+ by loading them up with electrons. These electrons are then passed through a sequence of proteins in the inner mitochondrial membrane and the energy used in this process is used to push protons across the membrane

  • Most of the energy-generating processes in cells take place in the mitochondria due to having a separate membrane-bound compartment to create a proton gradient

    → Once you have generated this proton gradient, the protons move back across the membrane through ATPase

    → ATPase break down ATP to produce energy for membrane transport systems

In this case, the enzyme system works in the other direction too

  • The proton gradient is used to drive the production of ATP

  • This is known as chemiosmosis

The whole process is called oxidative phosphorylation as:

  • Phosphorylating ADP to make ATP and oxygen is the final electron acceptor

    → the electrons move through the electron transport chain, giving up energy as they go until they bind with oxygen

    → essentially, you end up with water

If you were to start with glucose, you would end up with CO2, H2O and about 30 ATP.

Mitochondria are the result of an endosymbiont event 1.5 billion years ago where 1 prokaryote took to living inside another.

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