Fructolysis
[7] The products of fructose metabolism are liver glycogen and de novo lipogenesis of fatty acids and eventual synthesis of endogenous triglyceride.
[8] Once liver glycogen is replenished, the intermediates of fructose metabolism are primarily directed toward triglyceride synthesis.
Carbons from dietary fructose are found in both the FFA and glycerol moieties of plasma triglycerides (TG).
Excess dietary fructose can be converted to pyruvate, enter the Krebs cycle and emerges as citrate directed toward free fatty acid synthesis in the cytosol of hepatocytes.
Indeed, fructose may provide the bulk of the carbohydrate directed toward de novo TG synthesis in humans.
[9] Fructose consumption results in the insulin-independent induction of several important hepatic lipogenic enzymes including pyruvate kinase, NADP+-dependent malate dehydrogenase, citrate lyase, acetyl CoA carboxylase, fatty acid synthase, as well as pyruvate dehydrogenase.
Although not a consistent finding among metabolic feeding studies, diets high in refined fructose have been shown to lead to hypertriglyceridemia in a wide range of populations including individuals with normal glucose metabolism as well as individuals with impaired glucose tolerance, diabetes, hypertriglyceridemia, and hypertension.
An accumulation of fructose-1-phosphate following fructose ingestion inhibits glycogenolysis (breakdown of glycogen) and gluconeogenesis, resulting in severe hypoglycemia.
It is symptomatic resulting in severe hypoglycemia, abdominal pain, vomiting, hemorrhage, jaundice, hepatomegaly, and hyperuricemia eventually leading to liver and/or kidney failure and death.
This is why fructose is contraindicated for total parenteral nutrition (TPN) solutions and is never given intravenously as a source of carbohydrate.
Whether or not sufficient amounts of dietary fructose could be absorbed to cause a significant reduction in phosphorylating potential in liver cells remains questionable and there are no clear examples of this in the literature.
