Question

Leukotricnes A. synthesis begins with the addition of a hydroperoxy group to arachidonic acid. B. are inactivated by conversion to HPETEs. C. have an internal ring structure. D. are highly unstable, lasting only a fcw minutes. E. are converted to lipoxins.

Short answer

Answer: No, leukotrienes are not inactivated by conversion to HPETEs. HPETEs are actually intermediates in the synthesis of leukotrienes.

Step-by-step solution

Statement A

True. The synthesis of leukotrienes starts with the addition of a hydroperoxy group to arachidonic acid. Arachidonic acid is converted into a 5-hydroperoxyeicosatetraenoic acid (5-HPETE) intermediate by the enzyme 5-lipoxygenase. This is the first step in the formation of leukotrienes.

Statement B

False. Leukotrienes are not inactivated by conversion to HPETEs. In fact, HPETEs are intermediates in the synthesis of leukotrienes. The conversion of HPETEs to leukotriene A4 (LTA4) is facilitated by the enzyme leukotriene A4 hydrolase.

Statement C

True. Leukotrienes have an internal ring structure. Specifically, they have a conjugated triene structure, which possesses a carbon ring. This internal ring structure differentiates them from other eicosanoids, like prostaglandins.

Statement D

True. Leukotrienes are highly unstable and have a short lifespan, lasting only a few minutes. Due to their instability, they act locally at the site of inflammation, promoting a rapid response.

Statement E

True. Leukotrienes can be converted to lipoxins, which are anti-inflammatory lipid mediators. The conversion occurs through a process called transcellular biosynthesis, where leukotrienes produced in one cell are metabolized by enzymes in other nearby cells to form lipoxins. This conversion helps regulate the inflammatory response.

Key concepts

Arachidonic Acid

Arachidonic acid serves as a fundamental building block in the formation of various inflammatory mediators, including leukotrienes. Found within the phospholipids of cell membranes, this polyunsaturated fatty acid becomes available through the action of phospholipase A2, an enzyme activated during cellular injury or other initiating inflammatory stimuli.

Once freed, arachidonic acid enters pathways that lead to the synthesis of eicosanoids – a group of biologically active compounds. Of particular interest is the lipoxygenase pathway, where arachidonic acid is transformed into leukotrienes, known for their role in inflammation and allergic reactions. The initial step in leukotriene synthesis is arachidonic acid's conversion to a 5-hydroperoxyeicosatetraenoic acid (5-HPETE) intermediate, a reaction catalyzed by the enzyme 5-lipoxygenase.

Eicosanoids

Eicosanoids are a diverse group of signaling molecules, derived from arachidonic acid and other polyunsaturated fatty acids. They include prostaglandins, thromboxanes, leukotrienes, and lipoxins. These compounds play a pivotal role in the body's inflammatory and immune responses.

As local hormones, they typically act near the site of their production and are rapidly metabolized, which speaks to their short-lived nature. Considering their involvement in various physiological processes, such as vasodilation, clot formation, and modulation of the immune system, an imbalance in eicosanoid synthesis can lead to pathophysiological conditions, including asthma, arthritis, and cardiovascular disease.

Lipoxins

Lipoxins are a class of eicosanoids known for their anti-inflammatory and pro-resolving actions, and they are synthesized from arachidonic acid through the action of lipoxygenase enzymes. What distinguishes lipoxins is their contribution to the resolution phase of inflammation, where they facilitate the termination of the inflammatory response and promote healing.

Unlike leukotrienes that exacerbate inflammation, lipoxins counterbalance these effects, reflecting their role in maintaining homeostasis within the body's immune response. Their production is enhanced through transcellular biosynthesis, where intermediates produced in one cell type are taken up and converted by neighboring cells to lipoxins, exemplifying a coordinated cellular interaction during inflammation.

Inflammatory Mediators

Inflammatory mediators are substances that are released by cells in response to a variety of stimuli, including infection, tissue damage, or allergic reactions. These mediators, which include the likes of histamine, cytokines, leukotrienes, and prostaglandins, orchestrate the inflammatory process by attracting immune cells to the injury site, inducing fever, and causing pain and swelling.

While inflammation is essential for healing, unchecked or chronic inflammation can lead to tissue damage and contribute to diseases such as atherosclerosis, rheumatoid arthritis, and other chronic inflammatory conditions. Understanding the synthesis and regulation of inflammatory mediators is crucial for developing treatments for such inflammatory diseases.

5-Lipoxygenase

5-Lipoxygenase is an enzyme of critical importance in the metabolism of arachidonic acid to leukotrienes. This enzyme catalyzes the initial steps in the conversion of arachidonic acid into leukotrienes, including the production of the 5-hydroperoxyeicosatetraenoic acid (5-HPETE) intermediate.

Leukotrienes synthesized by this pathway are potent inflammatory mediators involved in allergic and inflammatory responses, with actions such as bronchoconstriction and the promotion of vascular permeability. The enzyme itself is regulated by a variety of factors and is a target for drugs aiming to manage conditions like asthma and other inflammatory disorders where leukotrienes play a significant role.