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Inhibitors of Metabolite Synthesis: How Sulfa Drugs Work

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  • 0:05 Metabolism
  • 1:15 Sulfa Drugs
  • 3:34 Synergism with Trimethoprim
  • 4:35 Lesson Summary
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Lesson Transcript
Instructor: Katy Metzler

Katy teaches biology at the college level and did her Ph.D. work on infectious diseases and immunology.

In our weight-conscious society today, there's a lot of talk about metabolism and how to speed it up. In this lesson, learn what metabolism really is and how antibiotics can work together to inhibit the bacterial metabolism.

Metabolism

When you hear the word 'metabolism,' you might think of skinny and not-so-skinny people and how people say things like, 'She has a super-fast metabolism; that's why she can eat whatever she wants and still look that good.'

What is metabolism, anyway? Metabolism is all of the chemical reactions that occur inside an organism to sustain its life. When people talk about speeding up their metabolism, they are talking about the chemical reactions involved in turning food into energy and burning calories. But, there are many other kinds of metabolism, too, since there are many chemical reactions and transformations that occur in all of our cells.

Bacteria have metabolisms too; that's how they turn the nutrients that they take in from the environment into all of the useful molecules they need for their day-to-day lives. And, the metabolism of bacteria has some major differences compared to our cells' metabolism. That means that, you guessed it, antibiotics that inhibit bacterial metabolism can be selectively toxic.

In this lesson, we'll learn about two antibiotics that inhibit bacterial metabolism: the sulfa drugs and trimethoprim.

Sulfa Drugs

Sulfa drugs are a class of synthetic drugs that all have a sulfonamide chemical group. These drugs have many different uses, but in this lesson, we will focus on the ones that are antibacterial. They are often used to treat bladder infections because they reach high concentrations in the urine. Sulfa antibiotics inhibit the pathway that bacteria use to synthesize folic acid, which is an important metabolite, or substance formed by metabolism for all cells.

Folic acid is a vitamin that is needed in order to make nucleotides and many amino acids. So basically, without folic acid, cells wouldn't be able to make DNA, RNA or most proteins. It's a pretty important metabolite.

We humans get folic acid from what we eat, such as leafy green vegetables, beans, nuts, and fruits. We can even buy it as a nutritional supplement. For example, women who are pregnant or who are hoping to become pregnant take folic acid to prevent birth defects in their new babies.

Pathway of folic acid synthesis in bacteria
diagram of folic acid synthesis in bacteria

But, bacteria have to make folic acid on their own. Above is the pathway that leads to folic acid synthesis in bacteria. You can see the enzymes involved and the metabolites that are made along the way. Drugs that inhibit folic acid synthesis are bacteriostatic because the bacteria can't reproduce if they don't have enough folic acid to make new DNA, RNA and proteins. They are also broad-spectrum drugs - they are effective against many types of bacteria.

Sulfa drugs like Sulfamethoxazole inhibit the enzyme that catalyzes the first step of this pathway. Sulfa drugs are competitive inhibitors of this enzyme, meaning that they compete with the real substrate of the enzyme, which is para-aminobenzoic acid and is called PABA for short.

Chemical structures of PABA and a sulfa drug
sulfa and paba structures

If we compare the structures of PABA and a sulfa drug, seen above, we can easily see how these drugs can be competitive inhibitors. They look a lot alike to us - and to the enzyme, too. If most of the copies of this enzyme in the bacterial cell are busy binding to sulfa drugs instead of to PABA, not much of the next metabolite in the pathway can be produced.

However, some of the next metabolite could be made, because chances are at least some of the enzymes will bind to PABA instead of the sulfa drug. That means that some folic acid could still be produced.

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