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Flavin metabolism during respiratory infection in mice
S Brijlal1, A V Lakshmi, M S Bamji
1Department of Biochemistry, National Institute of Nutrition, Jamai Osmania, Hyderabad, India.
Abstract:
Previous control studies carried out in children showed that respiratory infection alters riboflavin metabolism and leads to excessive urinary losses of the vitamin. In order to understand the nature of biochemical changes in riboflavin metabolism during respiratory infection, a study was carried out using the mouse as the experimental model, and Klebsiella pneumoniae as the infective organism. Mice were fed on either a low (0.5 mg/kg)- or high (13.3 mg/kg)-riboflavin semi-synthetic diet. Infection resulted in a 5-6-fold higher excretion of riboflavin in the urine of mice fed on the low-riboflavin diet. Higher erythrocyte FAD levels and lower liver FAD levels were also observed during infection. Of the four enzymes involved in the synthesis and breakdown of the flavin coenzymes studied, the activity of hepatic flavokinase (ATP: riboflavin 5'-phosphotransferase; EC 2.7.1.26) was significantly lower, and that of FAD synthetase (ATP: FMN adenylyltransferase; EC 2.7.7.2) was higher during riboflavin restriction and infection. The activity of FMN (acid) phosphatase (EC 3.1.3.2) was unchanged, whereas FAD (nucleotide) pyrophosphatase (EC 3.6.1.9) activity was significantly higher both with the low-riboflavin diet and during infection. Thyroid hormone is known to modulate flavokinase activity and, hence, thyroid status was assessed. Plasma triiodothyronine (T3) levels were not affected, but thyroxine levels were lower in the mice fed on the low-riboflavin diet. However, plasma T3 was significantly lower during infection, suggesting a mechanistic role for the hormone in the reduction of flavokinase activity.
Insights
Respiratory infection in mice alters riboflavin metabolism, increasing urinary losses and affecting key enzyme activities. Thyroid hormone levels, particularly triiodothyronine, may play a role in these biochemical changes.
Area of Science:
- Biochemistry
- Nutritional Science
- Infectious Disease
Background:
- Respiratory infections in children are known to disrupt riboflavin metabolism, causing increased urinary excretion.
- Understanding the biochemical mechanisms of riboflavin metabolism alterations during infection is crucial for nutritional management.
Purpose of the Study:
- To investigate the biochemical changes in riboflavin metabolism in a mouse model during Klebsiella pneumoniae infection.
- To identify specific enzyme activities and hormonal factors involved in altered riboflavin metabolism.
Main Methods:
- Mice were fed either a low or high riboflavin diet and subsequently infected with Klebsiella pneumoniae.
- Urinary riboflavin excretion, erythrocyte and liver FAD levels, and the activity of four key flavin-metabolizing enzymes were measured.
- Thyroid hormone levels (T3 and thyroxine) were assessed to evaluate their potential role.
Main Results:
- Infection significantly increased urinary riboflavin excretion, especially in mice on a low-riboflavin diet.
- Erythrocyte FAD levels increased while liver FAD levels decreased during infection.
- Hepatic flavokinase activity decreased, FAD synthetase and FAD pyrophosphatase activities increased during infection and/or riboflavin restriction.
- Plasma triiodothyronine (T3) levels decreased during infection, suggesting a role in reduced flavokinase activity.
Conclusions:
- Respiratory infection significantly alters riboflavin metabolism in mice, characterized by increased urinary losses and changes in FAD levels.
- Specific enzyme activities, including decreased flavokinase and increased FAD synthetase/pyrophosphatase, are implicated in these metabolic shifts.
- Reduced plasma T3 levels during infection may mechanistically link thyroid status to the observed decrease in flavokinase activity.