Download Fructose metabolism

Effect of excess fructose

major feature that distinguishes fructose metabolism from glucose entry into
glycolysis is the lack of feed back inhibition of fructokinase by its product F-1-P

Normally the rate limiting step in fructose metabolism is entry of fructose into the
cell, upstream of fructokinase

When blood fructose levels increase, for eg during infusion with fructose, entry into
the cell ceases to be rate limiting and the rate limiting step is shifted to aldolase B, ie
F-1-P is produced at a faster rate than it can be converted to DHAP and
glyceraldehyde. Under these conditions, even though F-1-P accumulates it cannot
inhibit its own production and it continues to increase.

Accumulation of F-1-P results in the trapping of Pi in F-1-P, depleting cellular Pi
and limiting the ability of cells to make ATP.

The resulting drop in ATP and increase in ADP and AMP activates PFK I increasing
glycolytic flux from glucose.

Increased glycolytic flux produces NADH at a rate greater than the "shuttle" systems
can regenerate NAD and excess pyruvate is converted to lactic acid leading to lactic
acidosis.

Although the increased glycolytic flux from glucose helps to restore ATP levels, the
low levels of Pi continue to be a limiting factor for glycolyis (why?) and ATP levels
continue to drop leading to possible liver damage.

Excess production of pyruvate may also result in “fatty liver”.