The hydrosome: an imaginary organelle for ammonia detoxification

¶ … a&P Lab

Design Project -- A&P Lab

Ammonia (NH3) is produced by cells located throughout the body; most of the production occurring in the intestines, liver, and the kidney, where it is used to produce urea. Ammonia is particularly toxic to brain cells, and high levels of blood ammonia can also lead to organ failure. The imaginary organelle referred to as a hydrosome functions in a manner that decreases the blood ammonia levels in people, thereby circumventing the need for medications such as to treatment to prevent hepatic encephalopathy and conditions associated with a failing liver. The hydrosome functions similarly to a primary lysosome, also containing a highly acidic interior with lytic enzymes called hydrolases. However, the waste disposal that the hydrosome conducts serves to convert ammonia to a water-soluble waste that is then excreted by the kidneys.

About this Organelle

I came up with the idea for this organelle because many diseases and disorders appear to be associated with high blood ammonia levels, and because hyperammonemia is a life-threatening medical emergency. If the human body contained an organelle with the capacity and function to reduce high levels of ammonia in the blood, it would be a tremendous help to people who have damaged livers or have contracted a disease that results in symptomatic high blood ammonia (Prasad, et al., 2007). Several drugs are useful in the treatment of hyperammonemia, including benzoate and phenylacetate (Prasad, et al., 2007). Both of these medications work by converting ammonia into water-soluble forms that the kidneys eliminate effectively (Prasad, et al., 2007).

The imagined organelle is referred to a hydrosome, as it functions similarly to a lysosome, and also contains a highly acidic interior with lytic enzymes called hydrolases, just as the lysosome does ("Interactive Concepts"). However, the waste disposal that the hydrosome conducts serves to convert ammonia to a water-soluble waste ("Interactive Concepts"). The hydrosome specializes in the breakdown of protein, which in turn triggers conversion of the ammonia by product ("Interactive Concepts"). In other words, the hydrosome enables the body to utilize proteins by breaking them down through the action of a specialized enzyme complex, but the hydrosome completes the process by eliminating the ammonia byproduct ("Interactive Concepts"). Here, the benefit of a labeled eukaryotic cell is apparent, as the cell could not survive the action of destructive enzymes without their containment in the membrane-bound lysosome. ("Interactive Concepts").

The inspiration for this imaginary organelle is the laxative called Lactulose that has a secondary use for the treatment of hepatic encephalopathy (Sharma, et al., 2009). However, the realism of a lactulose treatment regimen is questionable as it induces unstable bowel functioning and creates substantive social and management difficulties for the patient (Sharma, et al., 2009). A more acceptable, less intrusive way to address high blood ammonia levels in individual experiencing cirrhosis of the liver is highly desirable (Sharma, et al., 2009). Suspending disbelief -- as one does when watching a fantastical movie -- imagine that the cells of the body hold the answer to addressing potential liver failure (Sharma, et al., 2009). In this scenario, the organelle known as hydrosome makes radical drug therapies unnecessary.

Lactulose works to reduce the bacterial production of ammonia in the intestines, and the draws ammonia from the blood to the colon, from which it is purged with waste (Sharma, et al., 2009). Hydrosome acts in a more direct manner, acting directly on the proteins and the waste product of the protein breakdown (Sharma, et al., 2009). The membrane-bound hydrosome organelles are co-located within eukaryotic cells with lysosomes, to which they are morphologically similar (Sharma, et al., 2009). In the same manner as lysosomes, hydrosomes use endocytosis to engulf and break down proteins ("Interactive Concepts").

The enzymes complex releases a compound functions chemically like sodium phenylacetate and sodium benzoate, and that serves as an alternative to urea for the excretion of nitrogen waste (Batshaw, et al., 2001; Haberle, et al., 2012). The released compound has a nitrogen content that is identical to that of urea (i.e., two moles of nitrogen) (Batshaw, et al., 2001; Haberle, et al., 2012). Two moles of nitrogen are removed per mole of the phenylacetate-like compound that is conjugated with glutamine. One mole of nitrogen is removed per mole of the benzoate-like conjugated with glycine (Batshaw, et al., 2001; Haberle, et al., 2012). Both the glutamine and the glycine that are "used in these reactions are replaced by synthesis, which has the effect of reducing the nitrogen pool and attenuating the risk of ammonia and glutamine-induced neurotoxicity" (Batshaw, et al., 2001; Haberle, et al., 2012).

Considering This Assignment

This assignment served to entice study of the different organelles, but as the human cell is a maximally efficient system under normal circumstances, it was difficult to concoct a scenario that sounded at all feasible, yet was entirely imaginary. And, too, the assignment encouraged a review of drug therapies designed to assist with the production of an alternative to urea, which gave rise to the concept of a compound that would be released by the hydrosome as it worked to break down proteins. Fantastical though it was, the assignment did cause me to think about aspects of cellular functioning -- and particularly about the functioning of organelles that I otherwise would not have so fully addressed.

Works Cited:

Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. Journal of Pediatrics. 2001; 138: S46-55.

Haberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, Servais A, Valayannopoulos V, Lindner M, Rubio V, and Dionisi-Vici C. "Suggested guidelines for the diagnosis and management of urea cycle disorders." Orphanet Journal of Rare Diseases 2012: 7, 32. doi:10.1186/1750-1172-7-32. PMC 3488504. PMID 22642880 Retrieved http://www.ojrd.com/content/7/1/32

Interactive Concepts in Biochemistry - Interactive Animations. John Wiley & Sons Publishers, Inc. 2002. Retrieved http://www.wiley.com/legacy/college/boyer/0470003790/animations/cell_structure/cell_structure.htm

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. "Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy." Hepatology 2007: 45 (3): 549 -- 59.

Sharma BC, Sharma P, Agrawal A, and Sari SK. "Secondary Prophylaxis Of Hepatic Encephalopathy: An Open-Label Randomized Controlled Trial Of Lactulose vs. Placebo." Gastroenterology, 2009; 137: 885 -- 891. doi:10.1053/j.gastro.2009.05.056

Retrieved http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508509009044.pdf