Editing Fructose (section)

== Fructose metabolism ==

All three dietary monosaccharides are transported into the liver by the GLUT2 transporter.<ref>{{cite book | first=R | last=Quezada-Calvillo | title=Carbohydrate Digestion and Absorption | place=Missouri | publisher=Saunders, Elsevier | year=2006 | isbn=978-1-4160-0209-3 | pages=182–185 |author2=Robayo CC |author3=Nichols BL }}</ref> Fructose and [[galactose]] are [[phosphorylation|phosphorylated]] in the liver by [[fructokinase]] ([[Michaelis–Menten kinetics|K<sub>m</sub>]]= 0.5 mM) and [[galactokinase]] (K<sub>m</sub> = 0.8 mM), respectively. By contrast, glucose tends to pass through the liver (K<sub>m</sub> of hepatic glucokinase = 10 mM) and can be metabolised anywhere in the body. Uptake of fructose by the liver is not regulated by insulin. However, insulin is capable of increasing the abundance and functional activity of GLUT5, fructose transporter, in skeletal muscle cells.<ref>{{cite journal|last1=Hajduch|author2=Litherland GJ |author3=Turban S |author4=Brot-Laroche E |author5=Hundal HS |title=Insulin regulates the expression of the GLUT5 transporter in L6 skeletal muscle cells|date=Aug 2003|pmid=12914929|first1=E|volume=549|issue=1–3|pages=77–82|journal=FEBS Letters|doi=10.1016/S0014-5793(03)00773-7|s2cid=25952139 |doi-access=free|bibcode=2003FEBSL.549...77H }}</ref>

=== Fructolysis ===
{{Main|Fructolysis}}

The initial [[catabolism]] of fructose is sometimes referred to as [[fructolysis]], in analogy with [[glycolysis]], the catabolism of glucose. In fructolysis, the enzyme [[fructokinase]] initially produces [[fructose 1-phosphate]], which is split by [[aldolase B]] to produce the [[triose]]s [[dihydroxyacetone phosphate]] (DHAP) and [[glyceraldehyde]]. Unlike glycolysis, in fructolysis the triose [[glyceraldehyde]] lacks a [[phosphate group]]. A third enzyme, [[triokinase]], is therefore required to phosphorylate glyceraldehyde, producing [[glyceraldehyde 3-phosphate]]. The resulting trioses are identical to those obtained in glycolysis and can enter the [[gluconeogenesis|gluconeogenic]] pathway for glucose or glycogen synthesis, or be further catabolized through the lower glycolytic pathway to [[pyruvic acid|pyruvate]].

=== Metabolism of fructose to DHAP and glyceraldehyde ===
The first step in the metabolism of fructose is the phosphorylation of fructose to fructose 1-phosphate by fructokinase, thus trapping fructose for metabolism in the liver. Fructose 1-phosphate then undergoes [[hydrolysis]] by [[aldolase B]] to form DHAP and glyceraldehydes; DHAP can either be [[isomerization|isomerized]] to glyceraldehyde 3-phosphate by triosephosphate isomerase or undergo reduction to glycerol 3-phosphate by glycerol 3-phosphate dehydrogenase. The glyceraldehyde produced may also be converted to glyceraldehyde 3-phosphate by glyceraldehyde kinase or further converted to glycerol 3-phosphate by glycerol 3-phosphate dehydrogenase.  The metabolism of fructose at this point yields intermediates in the gluconeogenic pathway leading to glycogen synthesis as well as fatty acid and triglyceride synthesis.

=== Synthesis of glycogen from DHAP and glyceraldehyde 3-phosphate ===
The resultant glyceraldehyde formed by aldolase B then undergoes phosphorylation to glyceraldehyde 3-phosphate. Increased concentrations of DHAP and glyceraldehyde 3-phosphate in the liver drive the gluconeogenic pathway toward glucose and subsequent glycogen synthesis.<ref>{{cite journal | author1=MA Parniak |author2=Kalant N | title= Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose | year=1988 | journal=Biochemical Journal | volume=251 | pages=795–802 | pmid=3415647 | issue=3 | pmc=1149073 | doi=10.1042/bj2510795}}</ref> It appears that fructose is a better substrate for glycogen synthesis than glucose and that glycogen replenishment takes precedence over triglyceride formation.<ref>{{Cite journal|last1=Jia|first1=Guanghong|last2=Aroor|first2=Annayya R.|last3=Whaley-Connell|first3=Adam T.|last4=Sowers|first4=James R.|date=June 2014|title=Fructose and Uric Acid: Is There a Role in Endothelial Function?|journal=Current Hypertension Reports|language=en|volume=16|issue=6|pages=434|doi=10.1007/s11906-014-0434-z|issn=1522-6417|pmc=4084511|pmid=24760443}}</ref> Once liver glycogen is replenished, the intermediates of fructose metabolism are primarily directed toward triglyceride synthesis.<ref>{{Cite journal|last=Medina Villaamil|date=2011-02-01|title=Fructose transporter Glut5 expression in clear renal cell carcinoma|journal=Oncology Reports|language=en|volume=25|issue=2|pages=315–23|doi=10.3892/or.2010.1096|pmid=21165569|issn=1021-335X|doi-access=free|hdl=2183/20620|hdl-access=free}}</ref>

[[File:Fructose-glycogen.svg|thumb|center|400px|Metabolic conversion of fructose to glycogen in the liver]]

=== Synthesis of triglyceride from DHAP and glyceraldehyde 3-phosphate ===
Carbons from dietary fructose are found in both the [[free fatty acid]] and glycerol [[Moiety (chemistry)|moieties]] of plasma triglycerides. High fructose consumption can lead to excess [[pyruvate]] production, causing a buildup of [[Krebs cycle]] intermediates.<ref name=McGrane>{{cite book | first=MM | last=McGrane | title=Carbohydrate metabolism: Synthesis and oxidation | place=Missouri | publisher=Saunders, Elsevier | year=2006 | isbn=978-1-4160-0209-3 | pages=258–277}}</ref> Accumulated citrate can be transported from the [[mitochondrion|mitochondria]] into the [[cytosol]] of [[hepatocytes]], converted to [[acetyl CoA]] by citrate lyase and directed toward fatty acid synthesis.<ref name=McGrane /><ref name=Sul>{{cite book | first=HS | last=Sul | title=Metabolism of Fatty Acids, Acylglycerols, and Sphingolipids | place=Missouri | publisher=Saunders, Elsevier | year=2006 | isbn=978-1-4160-0209-3 | pages=450–467}}</ref> In addition, DHAP can be converted to glycerol 3-phosphate, providing the glycerol backbone for the triglyceride molecule.<ref name=Sul /> Triglycerides are incorporated into [[very-low-density lipoprotein]]s (VLDL), which are released from the liver destined toward peripheral tissues for storage in both fat and muscle cells.

[[File:Fructose-triglyceride.svg|thumb|center|400px|Metabolic conversion of fructose to triglyceride in the liver]]