Julianne Zedalis; John Eggebrecht

Learning Objectives

In this section, you will explore the following questions:

What are the differences in the ways aquatic animals and terrestrial animals can eliminate toxic ammonia from their systems?
What are the major byproducts of ammonia metabolism in mammals compared to fish, reptiles, birds, and insects?

Connection for AP^® Courses

Much information in this section is outside the scope for AP^®. However, the concepts provide an opportunity to apply concepts explored in previous chapters, including chemistry. Of the four macromolecules in biological systems, both proteins and nucleic acids contain nitrogen. During the breakdown (catabolism) of nitrogen-containing macromolecules, carbon, hydrogen, and oxygen are extracted and stored in the form of carbohydrates and fats. However, excess nitrogen must be excreted from the body because nitrogenous wastes tend to form toxic ammonia, which raises the pH of body fluids and disrupts homeostasis. The formation of toxic ammonia requires energy in the form of ATP and large quantities of water to dilute it out of a biological system. Aquatic animals, such as fishes, can release ammonia directly into the environment. Animals that excrete ammonia are said to be ammonotelic. Terrestrial animals, including mammals, must detoxify ammonia by converting it into relatively nontoxic forms such as uric acid or urea. Animals that secrete urea as the primary nitrogenous waste material are called ureotelic animals. Birds and reptiles excrete uric acid, a water-insoluble form of nitrogenous waste, thus reducing water loss. From an evolutionary standpoint, life likely started in an aquatic environment, so it not surprising that biochemical pathways like the conversion of ammonia to urea typical in mammals evolved to adapt to terrestrial conditions; more arid conditions probably led to the evolution of the uric acid pathway as a means of conserving water.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 2 of the AP^® Biology Curriculum Framework. The AP^® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP^® Biology course, an inquiry-based laboratory experience, instructional activities, and AP^® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 2	Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis.
Enduring Understanding 2.D	Growth and dynamic homeostasis of a biological system are influenced by changes in the system’s environment.
Essential Knowledge	2.D.2 Homeostatic mechanisms reflect both common ancestry and divergence due to adaptation in different environments.
Science Practice	6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices.
Learning Objective	2.25 The student can construct explanations based on scientific evidence that homeostatic mechanisms reflect continuity due to common ancestry and/or divergence due to adaptation in different environments.
Essential Knowledge	2.D.2 Homeostatic mechanisms reflect both common ancestry and divergence due to adaptation in different environments.
Science Practice	5.1 The student can analyze data to identify patterns or relationships.
Learning Objective	2.26 The student is able to analyze data to identify phylogenetic patterns or relationships showing that homeostatic mechanisms reflect both continuity due to common ancestry and change due to evolution in different environments.
Essential Knowledge	2.D.2 Homeostatic mechanisms reflect both common ancestry and divergence due to adaptation in different environments.
Science Practice	7.1 The student can connect phenomena and models across spatial and temporal scales.
Learning Objective	2.27 The student is able to connect differences in the environment with the evolution of homeostatic mechanisms.

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and excreted in urine. The overall chemical reaction by which ammonia is converted to urea is 2 NH₃ (ammonia) + CO₂ + 3 ATP + H₂O → H₂N-CO-NH₂ (urea) + 2 ADP + 4 P_i + AMP.

The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea, as shown in Figure 32.13. The amino acid L-ornithine gets converted into different intermediates before being regenerated at the end of the urea cycle. Hence, the urea cycle is also referred to as the ornithine cycle. The enzyme ornithine transcarbamylase catalyzes a key step in the urea cycle and its deficiency can lead to accumulation of toxic levels of ammonia in the body. The first two reactions occur in the mitochondria and the last three reactions occur in the cytosol. Urea concentration in the blood, called blood urea nitrogen or BUN, is used as an indicator of kidney function.

The urea cycle begins in the mitochondrion, where bicarbonate (HCO3) is combined with ammonia (NH3) to make carbamoyl phosphate. Two ATP are used in the process. Ornithine transcarbamylase adds the carbamoyl phosphate to a five-carbon amino acid called ornithine to make L-citrulline. L-citrulline leaves the mitochondrion, and an enzyme called arginosuccinate synthetase adds a four-carbon amino acid called L-aspartate to it to make arginosuccinate. In the process, one ATP is converted to AMP and PPi. Arginosuccinate lyase removes a four-carbon fumarate molecule from the arginosuccinate, forming the six-carbon amino acid L-arginine. Arginase-1 removes a urea molecule from the L-arginine, forming ornithine in the process. Urea has a single carbon double-bonded to an oxygen and single-bonded to two ammonia groups. Ornithine enters the mitochondrion, completing the cycle.

Figure 32.13 The urea cycle converts ammonia to urea.

Evolution Connection

Excretion of Nitrogenous Waste

The theory of evolution proposes that life started in an aquatic environment. It is not surprising to see that biochemical pathways like the urea cycle evolved to adapt to a changing environment when terrestrial life forms evolved. Arid conditions probably led to the evolution of the uric acid pathway as a means of conserving water.

Nitrogenous waste is eliminated in which forms?

ammonia and $\text K^+$ only
uric acid and urea only
urea, uric acid, and $\text K^+$
urea, uric acid, and ammonia

Nitrogenous Waste in Birds and Reptiles: Uric Acid

Birds, reptiles, and most terrestrial arthropods convert toxic ammonia to uric acid or the closely related compound guanine (guano) instead of urea. Mammals also form some uric acid during breakdown of nucleic acids. Uric acid is a compound similar to purines found in nucleic acids. It is water insoluble and tends to form a white paste or powder; it is excreted by birds, insects, and reptiles. Conversion of ammonia to uric acid requires more energy and is much more complex than conversion of ammonia to urea Figure 32.14.

Part A shows a photo of a freshwater fish and states that many invertebrates and aquatic species excrete ammonia. The chemical structure of ammonia is NH3. Part B shows a photo of a wood rat and states that mammals, many adult amphibians, and some marine species excrete urea. The chemical structure of urea is shown. Urea has two NH2 groups attached to a central carbon. An oxygen is also double-bonded to this central carbon. Part C shows a photo of a pigeon and states that insects, land snails, birds, and many reptiles excrete uric acid. The chemical structure of uric acid is shown. Uric acid has a six-membered carbon ring attached to a five-membered ring. Each ring has two NH groups embedded in it. An oxygen is double-bonded to each ring.

Figure 32.14 Nitrogenous waste is excreted in different forms by different species. These include (a) ammonia, (b) urea, and (c) uric acid. (credit a: modification of work by Eric Engbretson, USFWS; credit b: modification of work by B."Moose" Peterson, USFWS; credit c: modification of work by Dave Menke, USFWS)

Everyday Connection

Gout

Mammals use uric acid crystals as an antioxidant in their cells. However, too much uric acid tends to form kidney stones and may also cause a painful condition called gout, where uric acid crystals accumulate in the joints, as illustrated in Figure 32.15. Food choices that reduce the amount of nitrogenous bases in the diet help reduce the risk of gout. For example, tea, coffee, and chocolate have purine-like compounds, called xanthines, and should be avoided by people with gout and kidney stones.

Photo shows a toe that is swollen and red.

Figure 32.15 Gout causes the inflammation visible in this person’s left big toe joint. (credit: "Gonzosft"/Wikimedia Commons)

Why does gout often result in pain?

The urethra swells, making urination slower and more painful.
Uric acid crystals build up in the joints, resulting in painful body movements.
Ammonia begins to degrade the linking of the bladder, causing constant pain.
Urea is always highly concentrated, resulting in kidney stones that make urination painful.

Science Practice Connection for AP® Courses

Think About It

In terms of evolution, why is the urea cycle advantageous in terrestrial organisms? Why is it reasonable to conclude that the uric acid cycle of reptiles was an adaptation to arid environments?

Teacher Support

The questions are applications of AP^® Learning Objectives 2.25 and 2.27 and Science Practices 6.2 and 7.1 because the evolution of mechanisms to eliminate nitrogenous waste product reflect both common ancestry and diverge due to adaptation to different environments.

32.4 Nitrogenous Wastes