Folate enterohepatic circulation

Some of the unusual features of folic acid noled by investigators include (I) folic acid antagonists used in cancer therapy with temporary remissions (2) lolic acid occurs in chromosomes (3) folic acid is distributed throughout cells (4) needed for mitotic step metaphase to anaphase (5) antibody formation decreased in lolic acid deficiency (6) choline-sparing effects (7) analgesic in humans—pain threshold is increased (8) antisulfonatnide effects (9) enterohepatic circulation of folate (10) synthesized by psittacosis virus (11) concentrated in spinal fluid. 

A further problem with studies in patients maintained on long-term total parenteral nutrition is that they are not normal healthy subjects - there is some good medical reason for their treatment Furthermore, they will have little or no enterohepatic recirculation of vitamins, and hence may have considerably higher requirements than normal there is considerable enterohepatic circulation of folate (Section 10.2.1) and vitamin B12 (Section 10.7.1). 

There is considerable enterohepatic circulation of folate, equivalent to about one-third of the dietary intake. Methyl-tetrahydrofolate is secreted in the bUe, then reabsorbed in the jejunum together with food folates. In experimental animals, bUe drainage for 6 hours results in a reduction of serum folate to 30% to 40% of normal (Steinberg et al., 1979). There is very litde loss of folate jejunal absorption is very efficient, and the fecal excretion of 450 nmol (200 /xg) of folates per day largely represents synthesis by intestinal flora and does not reflect intake to any significant extent. 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

Protein-free plasma folate is filtered at the glomerulus and most is reabsorbed by the proximal renal tubules. Consequently, intact urinary folate is only a small percentage of intake. Folate is predominantly excreted by catabolism foUowing cleavage of the C9-N10 bond to produce p-aminobenzoylpolyglutamates, which are then hydrolyzed to monoglutamates and hT-acetylated before excretion. Biliary excretion of folate has been estimated at about 100 Xg/day, but much of this is reabsorbed in an enterohepatic circulation. Fecal losses have been studied by radiolabeling and have been found to be similar in type and quantity to urinary losses. ... 

A6. Anonymous, Alcohol and the enterohepatic circulation of folate. Nutr. Rev. 38, 220-223... 

Folate deficiencies frequently occur in individuals with chronic alcoholism. A number of factors are involved inadequate dietary intake of folate direct damage to intestinal cells and brush border enzymes, which interferes with absorption of dietary folate a defect in the enterohepatic circulation, which reduces the absorption of folate liver damage causing decreased hepatic production of plasma proteins and interference with kidney resorption of folate. 

The hver, which stores half of the body s folate, takes up much of the folate from the portal circulation uptake may be through active transport or receptor-mediated endocy-tosis. Within the liver, FH4 is reconjugated to the polyglutamate form before being used in reactions. A small amount of the folate is partially degraded, and the components enter the urine. A relatively large portion of the folate enters the bile and is subsequently reabsorbed (very similar to the fate of bile salts in the enterohepatic circulation). 

FIG. 2. Schematic diagram of whole-body folate metabolism. Dietary forms of polyglutamyl folates are deconjugated in the jejunum (vertical rectangle on left) by mucosal and, to a lesser extent, pancreatic hydrolases. Secretion of folate in bite accounts for an enterohepatic circulation that has not been incorporated into modeling. Tissues behave, at least superficially, as a large, kinetically slow, pool. 

The liver rapidly absorbs from 10 to 20% of dietary folate, with a preference for non-methylated and non-reduced derivatives, while peripheral tissues are enriched in reduced and methylated functional derivatives. Folate is mainly stored in the liver. Hepatic folates are partly excreted into the bile enterohepatic circulation and reabsorbed (Steinberg et al. 1979). This is one of the mechanisms involved in the recirculation of folate. Regarding renal elimination, folate is filtered by the glomerulus and reabsorbed into the proximal tubule. The daily urinary excretion of intact folates is between 1 to 12 pg. When the serum plasma folate concentration is very high, it is possible to overwhelm the renal reabsorption capacity in this case, folate derivatives are excreted in the urine. Due to the possible production by the gut microflora, fecal folate levels are quite high. 

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