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How to pronounce fructosuria in English?

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The purpose of this video is to describe the normal pathway of fructose metabolism
and then use this information to show the metabolic disturbance in hereditary fructose intolerance and its biochemical consequences
First off, fructose is a monosaccharide that is widely found in nature in fruits, vegetables, and honey
It can be ingested as free fructose, or come from sucrose
which is digested by brush-border enzyme sucrase
to form 1 unit each of glucose and fructose
It is then absorbed across the small intestinal enterocytes in a process
facilitated by the GLUT 5 and GLUT 2 transport proteins.
Our capacity for fructose absorption in each individual varies but is often incomplete.
So when someone consumes too much fructose
it exceeds their capacity for absorption in the small intestine
and the unabsorbed fructose travels to the colon
Here it is fermented by colonic bacteria, producing gas and fluid,
leading to symptoms similar to that seen in lactose intolerance.
While this is often labeled as dietary fructose intolerance, it is not a disease,
and should not be confused with hereditary fructose intolerance.
All fructose absorbed into the blood must travel first to the liver,
where roughly 75% is taken up by liver cells through a similar transport mechanism.
The remainder enters then systemic circulation,
from which the kidney and small intestine absorb and metabolize what is left.
So how is fructose metabolized in these tissues?
The enzyme fructokinase first catalyzes the phosphorylation of fructose to fructose-1-phosphate.
From here, Aldolase acts on F-1-P to split it into DHAP (dihyroxyacetone phosphate),
and glyceraldehyde (GA).
Aldolase B is only found in liver, kidney, and small intestine,
as is triokinase, which catalyzes phosphorylation of glyceraldehyde to glyceraldehyde 3-phosphate (GA 3-P).
From here, GA 3-P and DHAP are actually intermediates in the pathways of glucose metabolism,
so fructose has the same metabolic fate when the pathway is running normally.
GA 3-P can either undergo the final reactions of glycolysis to produce pyruvate,
which is metabolized and enters the Krebs cycle.
Alternatively, it can undergo the aldolase-mediated reversible conversion of GA 3-P
and DHAP to fructose-1,6-bisphosphate, which subsequently can complete gluconeogenesis
and form glucose.
Finally, shown here is the pathway for glycogen breakdown aka glycogenolysis
which is important in mobilizing glucose from the liver.
Note that the aldolase enzyme has been mentioned in 2 enzymatic steps. It comes in 3 isoforms.
Aldolase A and C are expressed in muscle and brain, and catalyze reversible cleavage of fructose-1,6-bisphosphonate as steps in gluconeogenesis and glycolysis.
Aldolase B isoform, however,
is limited to liver, kidney and small intestine and catalyzes both aldolase reactions,
Its role as a fructose-1-phosphate aldolase is not duplicated in other tissues,
and will be of great interest as we move on to discuss
hereditary fructose intolerance, an important disorder of fructose metabolism.
Hereditary fructose intolerance, or HFI, occurs in 1 in 20,000 individuals,
and is a result of mutations in the aldolase B gene (ALDOB) on chromosome 9.
More than 40 disease-causing mutations have been identified,
all of which result in a dysfunctional aldolase B protein
whose enzymatic activity is reduced to less than 15% of normal values.
The clinical and biochemical manifestations of this condition result from acute or chronic exposure to fructose
or sugars that are metabolized to fructose such as sucrose and sorbitol.
As mentioned, most issues in HFI relate to the resulting inability of altered
aldolase B to cleave fructose-1-phosphate to DHAP and glyceraldehyde.
Here’s the crux of the problem.
In that first fructokinase reaction in fructose metabolism, ATP is consumed.
Aldolase B cleavage of the fructose-1-phosphate is needed
to produce DHAP and glyceraldehyde, intermediates that can enter the glycolytic pathway
to regenerate ATP and reclaim inorganic phosphate in the form of ATP.
Unfortunately in HFI, because enzyme activity is so low,
phosphate becomes trapped in the fructose-1-phosphate substrate,
which accumulates in the cell following fructose ingestion.
This trapping takes phosphate out of the intracellular pool,
and leads to net ATP consumption.
Meanwhile, the deficient aldolase B can also no longer condense
DHAP and GA 3-P, which normally promotes endogenous glucose production
through gluconeogenesis. The consequences all stem from these primary abnormalities.
Hypophosphatemia occurs because the liver sequesters phosphate from the serum
in adaptation to intracellular phosphate depletion.
Hypoglycemia, the other prominent feature after fructose ingestion, occurs because of inhibition of gluconeogenesis and glycogenolysis.
ATP/phosphate depletion impair glycogenolysis, which requires these substrates
Gluconeogenesis is inhibited because of the primary enzyme deficiency.
Fructose-1-phosphate accumulation may also directly inhibit enzymes in these pathways.
As a result, hypoglycemia ensues as the liver cannot produce or mobilize glucose.
Another consequence of this is that after chronic ingestion, the liver stores excess glycogen,
leading to hepatomegaly and steatosis.
Intracellular depletion of ATP and phosphate also promotes AMP deaminase,
And other enzymes involved in purine degradation,
leading to increased production of uric acid,
hyperuricemia, and increased urinary excretion of uric acid.
Magnesium is bound to intracellular ATP,
so increased Mg release following ATP depletion may lead to hypermagnesemia.
ATP depletion also leads to reduction in all cellular processes within the affected tissues,
and fructose-1-phosphate accumulates at what is thought to be toxic intracellular levels.
The combination of these factors is thought to lead to cell necrosis in both the kidney and liver.
The liver is often injured acutely, with serum ALT and AST often increased by more than two-fold after fructose ingestion.
Young infants often present acutely with liver impairment associated with prolonged INR,
edema, and conjugated hyperbilirubinemia,
but acute liver failure is exceedingly rare.
Liver disease can be progressive, however, as older infants and children can present after chronic fructose consumption
with hepatomegaly and failure to thrive, and later chronic liver failure.
Acute and/or chronic renal disease have also been documented,
specifically, proximal tubular dysfunction.
Usually, this disturbance resolves when fructose intake stops.
The same is true for the liver as long as the disease is caught early
although sometimes, even once fructose is eliminated
hepatomegaly and hepatic steatosis may persist for a considerable time
Finally, fructose-1-PO4 accumulation provides negative feedback
to fructokinase, resulting to a build up of intracellular fructose,
which limits hepatic fructose uptake because of a change in concentration gradient.
This results in fructosemia (high fructose in the blood) and fructosuria.
This concludes the screencast.
I hope this was helpful in explaining some of the concerns that arise and noted in HFI.