Sunday, February 10, 2019

Introduction to Metabolism

Have a basic understanding of metabolism and the roles of the metabolic pathways presented. Appreciate the role of enzymes, “high energy” carriers, cofactors & coenzymes in metabolism. Appreciate how metabolic pathways are linked to provide the body with useful fuels.


Understand the need for controlling enzyme activity, including: allosterism, inhibitors, inhibition and feedback.

It is important to control enzyme activity because, as mentioned here, controlling enzyme activity controls which reactions are taking place within the cell. Furthermore, if you are trying to build molecules up, you don't want the reactions that destroy those same molecules to be taking place at the same time, otherwise your efforts at making molecules would be in vain. Thus, it is important to make sure that synthesis and degradation reactions aren't proceeding at exactly the same time.

  • Allosterism- Sometimes substances can bind to enzymes in a place other than the active site. When that happens, the enzyme might become more or less able to carry out its function.
  • Inhibitors- Inhibitors are substances that bind to an enzyme and stop it from working. They can be competitive (bind to the active site), noncompetitive (bind to a site other than the active site), or uncompetitive (bind both the enzyme and the substrate at the same time).
  • Inhibition- Preventing an enzyme from carrying out its normal role.
  • Feedback- Sometimes, the products of a reaction can provide feedback to the enzymes, inhibiting further production of product. This is important for making sure that cells don't waste their energy producing something if there is already a lot of it in the cell.

Know the classes of enzymes and their functions.

Most enzymes end with -ase and have fairly logical names. For instance, oxidoreductases catalyse oxidations and reductions, transferses catalyse the transfer of functional groups, and proteases break down proteins. Two classes to be particularly careful about are kinases and phosphatases: kinases ADD (not remove!) a phosphate group, while phosphatases remove phosphate groups.

Appreciate the role of redox reactions.


Know that NADH & FADH2 are important electron carriers.

NADH and FADH2 are essential for the electron transport chain (a part of the process of producing ATP)- see here.

Understand the significance of Redox Potential values.

Redox potentials are a measure of how readily a substance will donate electrons. The more negative the redox potential (E') value, the more readily the substance donates electrons. See here for an example of redox potentials in action.

Have a basic understanding of the metabolic pathways in glucose catabolism.


Realise acetyl CoA is an important metabolic intermediate.

Acetyl CoA is a product of the breakdown of carbohydrates, lipids, AND proteins. It is able to enter the TCA cycle, which is where lots of ATP is produced. It is also able to be turned into ketone bodies, which can be a useful alternative fuel source if glucose is unavailable. Hence, acetyl CoA is an important metabolic intermediate.

Know the metabolic events which occur in different organs: liver, muscle, brain, red blood cell, adipose.

Liver

The liver is basically a one-stop-shop for metabolism. It can perform glycolysis, gluconeogenesis, make ribose via the Pentose Phosphate Pathway, synthesise and degrade fatty acids, make ketone bodies, and so on. Pretty much the only thing it can't do is use the ketone bodies that it makes, as that would require ketone bodies to be converted back to acetyl CoA before entering the TCA cycle.

Muscle

Skeletal muscle is basically a huge glucose hog, as it can store loads of glycogen but can't export it to share with any other tissues. It can also use fatty acids and ketone bodies. Cardiac muscle also has a glycogen store (though relatively small), and can also use fatty acids and ketone bodies, but fatty acids are the fuel of choice when at rest.

Brain

Glucose is the primary fuel of the brain, as it cannot use fatty acids. The brain can, however, use ketone bodies for fuel- desperate times call for desperate measures!

Red blood cells

Red blood cells have no mitochondria, so they can only perform pathways that take place in the cytosol. Specifically, they pretty much only perform the pentose phosphate pathway to make NADPH (a crucial component of the red blood cell membrane), and glycolysis to form lactate (as the pyruvate cannot enter the TCA cycle).

Adipose

The main function of adipose (fat) tissue is to store and release fatty acids. It can, however, also perform glycolysis and the pentose phosphate pathway, as well as store small amounts of glycogen.

Know the general consequences of enzyme deficiency on metabolic pathways.

If an enzyme is deficient, the chemical reactions that it catalyses will not proceed (at least not at a reasonable rate). Hence, you may get a build-up of the substrate or too little of the product. Either or both of these instances can be detrimental to the cell.

Know the “common” symptoms of inborn errors of metabolism.

Most of the common symptoms of inborn errors of metabolism are pretty vague and non-specific, such as vomiting, lethargy, and respiratory distress. Sometimes, though, there might be a more specific sign, such as an unusual odour.

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