Sufficient to saturate FAD sites of glutathione reductase (GR)
GR activity measured* with FAD (A)
GR activity measured* without FAD
Insufficient to saturate FAD sites of glutathione reductase (GR)
GR activity gr activity measured* measured*
with FAD without FAD
Figure 3 Basis of the glutathione reductase for riboflavin status: (A) riboflavin sufficient; (B) riboflavin deficient. *Reaction of oxidized glutathione with reduced nicotinamide adenine dinucleotide phosphate.
and graded supplements can be given to estimate human requirements.
There are minor operational differences among different published versions of the analytical procedure for 'EGRAC,' which result in small between-laboratory differences in the interpretation of the normal range and there are also some instances of specific factors that cause ambiguity of interpretation. The best known of these is the human genetic variant resulting in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase EC 22.214.171.124) deficiency. Both homo-and heterozygotes are affected, and in such subjects erythrocyte glutathione reductase becomes almost saturated with FAD, even when they are riboflavin deficient. Other tests of status, such as high-performance liquid chromatography (HPLC) measurement of riboflavin in blood fractions, are then required.
Some groups of people have increased requirements for riboflavin, which is related to special metabolic states. There is, for instance, a progressive increase in requirement during pregnancy, followed by a decrease during lactation. Babies exposed to phototherapy for neonatal jaundice also have increased requirements. In certain circumstances, the use of oral contraceptives may increase requirements, but the evidence is conflicting. The largest and most dramatic increases in requirements have been seen (as noted above) in a subgroup of people with inborn metabolic errors leading to dicarboxylicaciduria and associated clinical abnormalities. Although certain drugs are known to affect riboflavin status indices, there is no clear consensus on the question of the need for supplements by people who are prescribed such drugs - clearly this area needs further study.
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