Does fluoroacetate inhibit glycolysis?

Does fluoroacetate inhibit glycolysis?

Citrate and fluorocitrate are allosteric inhibitors of phosphofructokinase-1 (PFK-1), a key enzyme in glycolysis.

What is fluoroacetate why is it used?

Sodium fluoroacetate is an acute toxicant predacide which is used against coyotes which prey on sheep and goats. Registered end-use products are injected into the rubber reservoirs of the Livestock Protection collars, also referred to as the “toxic collar”, which are strapped to the throats of sheep or goats.

How does fluoroacetate affect cellular respiration?

Fluoroacetate enters the tricarboxylic acid (Krebs) cycle in place of acetate and is converted to fluorocitrate, which competitively inhibits aconitase and thereby prevents the conversion of citrate to isocitrate. This leads to citrate accumulation, reducing glucose metabolism, energy stores, and cellular respiration.

Where does fluoroacetate come from?

Background. Sodium fluoroacetate is the salt of a naturally occurring toxin which is found in Australia, Brazil, and Africa. Naturally occurring fluoroacetate can be found in Gastrolobium minus (family: Fabaceae), a flowering plant in Western Australia and often referred to as the ‘poison pea.

How does sodium fluoroacetate work?

Fluoroacetate combines with coenzyme A (CoA-SH) to form fluoroacetyl CoA, which can substitute for acetyl CoA in the tricarboxylic acid cycle and reacts with citrate synthase to produce fluorocitrate, a metabolite of which then binds very tightly to aconitase, thereby halting the cycle.

What type of inhibitor is fluoroacetate?

Fluoroacetate has been called a “Trojan horse inhibitor.” It enters the citric acid cycle and is converted by acetyl-CoA-synthetase to fluoroacetyl-CoA which is converted by citrate synthase to fluorocitrate. It isn’t inhibitory until it reacts with aconitase and blocks the citric acid cycle.

What plants contain fluoroacetate?

All of the plants containing fluoroacetate belong to the families Fabaceae, Rubiaceae, Bignoniaceae, Malpighiaceae and Dichapetalaceae [11]. Fluoroacetate is found in these tropical and subtropical plants generally at low concentrations although some are able to accumulate fluoroacetate in high concentrations [12].

What are rodenticides used for?

Rodenticides are pesticides that kill rodents, including mice and rats. They are often formulated as baits with attractive substances like peanut butter or molasses. Rodenticide baits can provide short-term control of rodent infestations.

What enzyme is inhibited by sodium fluoroacetate?

enzyme aconitase
Sodium Fluoroacetate This inhibits the enzyme aconitase, which inhibits conversion of citrate to cis-aconitic acid/isocitrate. This inhibition will lead to a buildup of citric acid resulting in convulsions and death from cardiac failure or respiratory arrest.

What kind of inhibitor is fluoroacetate?

Trojan horse inhibitor
Fluoroacetate has been called a “Trojan horse inhibitor.” It enters the citric acid cycle and is converted by acetyl-CoA-synthetase to fluoroacetyl-CoA which is converted by citrate synthase to fluorocitrate. It isn’t inhibitory until it reacts with aconitase and blocks the citric acid cycle.

What are the advantages of rodenticides?

With rodenticides, you can control and get rid of more pests with less bait. Child Resistant — Some rodenticide bait stations, like the VictorⓇ Fast-Kill BrandⓇ Mouse and Rat Bait Stations, come with features to give you peace of mind when placing rodenticides in a house with children.

How effective are rodenticides?

The low-dose baits (25 ppm) were consequently tested under field conditions in two populations showing 95.7% and 99.8% efficacy. The obtained results highlighted the good efficacy of the new baits based on low-dose brodifacoum in non-resistant mouse populations.

What is the pathophysiology of fluoroacetate poisoning?

The features of fluoroacetate poisoning are primarily the consequences of severe impairment of oxidative metabolism by impairment of the tricarboxylic acid cycle, as well as inhibition of mitochondrial citrate transport leading to accumulation of citrate.

What is the reaction between oxaloacetate and fluoroacetate?

Fluoroacetate, which is considered to be nontoxic, is metabolized to monofluoroacetic acid by hydrolysis and reacts with coenzyme A to form fluoroacetyl CoA. This product combines with oxaloacetate in the Krebs cycle and is converted to fluorocitrate, a toxic metabolite.

What is the effect of fluoroacetate on the Krebs cycle?

Krebs cycle needs sufficient amount of oxygen to proceed. Fluoroacetate causes patients to have symptoms such as hard to breathe, which will cause less intake of oxygen. Krebs cycle will be inhibited. Due to ATP depletion, It will also inhibit high-energy consuming reactions such as gluconeogenesis.

How is fluoroacetate excreted from the body?

Fluoroacetate is converted to the ultimate toxicant, fluorocitrate. Fluoroacetate is distributed to lipid-rich organs, such as the liver, brain, and kidneys. Fluoroacetate is primarily eliminated through urine. Up to 50% of the fluoroacetate is excreted unchanged in the urine by 72 h following administration.

author

Back to Top