Summary: Medical Biochemistry And Pathophysiology

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  • Feedback inhibition

  • What is the committed step?

    The committed step is the first irreversible reaction in a biosynthetic pathway. It is usually inhibited by the final product in the pathway.
  • Drug development

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  • What doe cytochrome P450 (CYP) enzymes do?

    They are mono-oxygenases. They oxidize the substrate and incorporate oxygen atoms into it (So oxygen is part of the reaction).
  • How do CYP enzymes assist in the metabolism of foreign substances such as drugs?

    CYP enzyme can metabolize foreign chemicals like drugs. The drugs receive an oxygen (mono-oxidized) and therefore can form better hydrogen bonds so they can be more easily excreted. 
  • What happens to the NAD/NADH ratio in the liver cell when ethanol is oxidized? And what are the consequences for the citric acid cycle and gluconeogenesis?

    There will be more NADH. The ratio depends on how many electrons are available and how many food molecules are getting oxidized. The citric acid cycle is inhibited because the cycle needs NAD+ to oxidize intermediates. This results in the modification of pyruvate (which can't enter the CAC) into lactate, so you won't have pyruvate to make glucose. 
    Gluconeogenesis can't tale place. There will be little glucose in the blood (hypoglycemia).

    So, there are 2 consequences: hypoglycemia and lactate acidosis.

    * Because lactate accumulates in the liver, it will also accumulate in the blood (lactate acidosis).
  • Why do persons who consume excessive amounts of alcohol develop a fatty liver?

    The citric acid cycle is blocked because of a shortage of NAD+ . So, you will have high levels of acetyl-CoA and NADH, both stimulating fatty acid synthesis. As a result, you will get storage of fats in the liver (fatty liver).
    The fat breakdown is also inhibited because of sufficient amounts of NADH. 
  • On what does the Absorption rate of a drug depend?

    - Solubility
    - If it can cross a membrane (hydrofobic)
    - Molecular weight (<500)
    - Number H-bond donors (<5)
    - Number H-bond acceptors (<10)
    - Partition coofficient log(P) <5

    * Partition coofficient is a way to measure solubility in water relative to organic (needs to cross the membrane)
    * Rules of 5
  • How does the distribution of drugs go?

    Hydrophobic compounds binds to albumin (they do not dissolve freely in the blood)
  • How does the Metabolism of drugs go?

    In 2 phases, first oxidation and then conjugation. 
    - Phase I: make them more soluble (with the help of CYP enzymes)
    - Phase II: 'flag' them for transport/removal (glutathione, glucoronic acid & sulfate).
  • How are drugs excreted?

    Drugs go via the portal vein into the liver. They are there oxidized and conjugated and go through the bile duct. Some drugs can pass this cycle multiple times (enterohepatic cycling).
  • Enzyme Inhibitors

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  • What is an irreversible inhibitor?

    An irreversible inhibitor dissociates very slowly from its target enzyme because it has become tightly bound to the enzyme (covalently & noncovalently) 


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