Thursday, October 16, 2014

Blood. It’s What’s For Dinner.

Halloween will soon be upon us, and our streets will once again be filled with ghosts, zombies, Lady Gagas, and other terrifying creatures of the night. And you can “count” on seeing a few vampires as well, lurking through the shadows in search of blood.

Okay, so maybe not all vampires are scary. If you have trouble sleeping Halloween night, check out this movie and “howl” with laughter.
The practice of feeding on blood, known as hematophagy, is actually a lot more common than you might realize. A wide variety of creatures suck blood, including bats, ticks, leeches, vampire finches, politicians, and so on. Similar to milk, blood is an easily accessable liquid meal containing many proteins and lipids – it does a body good. Many people who are not undead also consume blood, either directly or cooked in foods like sausages, pancakes, and soups. As seen on an episode of the hit reality TV show, Survivor (Africa), the Maasai of Tanzania get their blood straight out of the tap. They cut the neck of cattle just enough to collect blood to make a milk-blood cocktail, and then allow the wound to heal for another drink in the future.  

But not all creatures can easily digest blood. Plasmodium, the single-celled parasite that causes malaria, had to evolve some clever strategies to deal with the toxic byproducts that accumulate during the breakdown of hemoglobin, the oxygen-carrying molecule that comprises approximately 96% of the red blood cells’ dry content by weight in mammals.

(a) The malaria parasite is injected into the host’s bloodstream by another bloodsucker, the mosquito. (b) Sporozoites migrate to the liver and develop into merozoites that invade red blood cells (c). (d) Gametocytes then develop in red blood cells that can be taken up by another mosquito, which will bite a new host to continue the cycle. Life cycle image from:   

While in the red blood cell, the parasite replicates like mad. That feverish replication requires a lot of raw materials, like amino acids to build new parasite proteins. Fortunately for the parasite, those red blood cells are rich in hemoglobin, which can be broken down into amino acids the parasite can use. However, as any malarial parasite (or Dr. Dan Goldberg) will tell you, the digestion of hemoglobin is not trivial. As the parasite’s enzymes break it down, the free heme molecules that are released as by-products within the parasite’s food vacuole are highly toxic. If these heme molecules are not disposed of properly, the parasites would die in their own waste.

Bloodsucking humans have an enzyme called heme oxygenase, which can degrade toxic heme; so unlike the malaria parasite, vampires do not need to worry about heme toxicity. But they do have trouble keeping their teeth clean!

So how does Plasmodium solve this problem? If heme were lemons, hemozoin would be the lemonade. The parasite neutralizes the toxic heme subunits by sticking them together into an inert crystal structure called hemozoin. Hemozoin crystals are non-toxic and provide decorative conversation pieces to dress up the parasite’s food vacuole. Probably looks a lot like Shirley MacLaine’s house.

Hemozoin crystals formed within the food vacuole of the malarial parasite.

Incidentally, the process of building hemozoin turns out to be an Achilles’ heel for malaria, as a number of antimalarial drugs work by interfering with hemozoin formation. Unfortunately, the malarial parasite is remarkably adaptive and has evolved multiple ways to become resistant to several drugs in this family.

Contributed by:  Bill Sullivan
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Goldberg, D. (2013). Complex nature of malaria parasite hemoglobin degradation Proceedings of the National Academy of Sciences, 110 (14), 5283-5284 DOI: 10.1073/pnas.1303299110

Gorka AP, de Dios A, & Roepe PD (2013). Quinoline drug-heme interactions and implications for antimalarial cytostatic versus cytocidal activities. Journal of medicinal chemistry, 56 (13), 5231-46 PMID: 23586757

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