Fructosephosphates
Fructose phosphates are sugar phosphates based upon fructose, and are common in the biochemistry of cells.[1] A fructose phosphate is formed when fructose is phosphorylated through the addition of an inorganic phosphate group (Pi).
Fructose is a naturally occurring monosaccharide and is referred to as a “fruit sugar” due to existing in virtually every fruit.[2] Fructose is a six-carbon molecule and can be drawn as a linear chain (Fischer Projection) or a ring-like structure (Haworth Projection), consisting of carbon and hydroxyl groups. Inorganic phosphate is an anion that plays a fundamental role in various key biological processes.[3]
Fructose phosphates play integral roles in many metabolic pathways, particularly glycolysis, gluconeogenesis, oxidative phosphorylation, and lipogenesis.[4] Furthermore, biomedical research has increasingly demonstrated the role of fructose phosphates in metabolic processes and how dysregulation of their production or metabolism can contribute to several human diseases.[5]
Role in Metabolism
[edit]Fructose phosphorylation and dephosphorylation events involve specific enzymes that either add or remove phosphate groups depending on the cellular context. All known enzymatic phosphorylations of fructose (i.e., hexokinase, fructokinase, or phosphofructokinase-1) are ATP-dependent.[6] All of these enzymes use Adenosine Triphosphate (ATP) as the phosphate donor to transfer the γ-phosphate to fructose or fructose-derivatives under normal physiological conditions.[7] On the other hand, dephosphorylation reactions of fructose are not ATP-dependent, but rather are hydrolytic and catalyzed by phosphatases (e.g., fructose 1,6-bisphosphatase, fructose 2,6-bisphosphatase, or phosphoprotein phosphatase).[6] Furthermore, these reactions do not require ATP due to being energetically favorable, and thus, use water to cleave the phosphate ester bond and release a Pi.
Examples of major biologically active fructose phosphates are:
- Fructose 1-phosphate
- Fructose 2-phosphate
- Fructose 3-phosphate
- Fructose 6-phosphate
- Fructose 1,6-bisphosphate
- Fructose 2,6-bisphosphate
Each fructose phosphate plays a specific role in metabolism. For example, fructose 2,6-bisphosphate is an important allosteric regulator for the correlated regulation of glycolysis and gluconeogenesis based on hormonal nutritional signals.[6] However, if fructose 2,6-bisphosphate levels become unregulated and result in a decrease in its production, gluconeogenesis is favored over glycolysis, which contributes to hepatic glucose output in diabetes.[8]
Real-World Applications
[edit]Because of fructose phosphates' critical role in metabolism, their relevance spans to clinical, dietary, and therapeutic contexts.
(1) Metabolic Disorders[5]
- Hereditary Fructose Intolerance (HFI)
- Fructose 1,6-Bisphosphate Deficiency
- Metabolic Syndrome and Obesity
(2) Nutritional Science and Guidelines[9]
- Dietary fructose should be consumed in moderate amounts from around 25-40 g/day. However, the value may be different according to an individual's body structure and composition.
- Excessive intake of fructose may result in negative health outcomes, but should not be taken to be the only factor for any metabolic disease.
(3) Therapeutic and Pharmacological Applications[10]
- Targeting the inhibition of ketohexokinase as potential therapeutic strategy for fructose-induced metabolic disease.
- Involvement of pharmaceutical companies to develop the appropriate drugs for clinical trials.
References
[edit]- ^ Dikow, A. L; Lolova, I; Ivanova, A; Bojinov, S (1969). "Biochemical and histochemical studies of fructosephosphate aldolase in tumors of the nervous system. Isoenzymes of fructosephosphate aldolase. 8". Zeitschrift für klinische Chemie und klinische Biochemie. 7 (6): 606–13. PMID 4312415.
- ^ Shintani, Tomoya; Lema-Perez, Laura; Shintani, Hideya (2021-09-01), James Martins, Ian (ed.), "The Sugars with the Potential to Prolong Human Life" (PDF), Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic, IntechOpen, doi:10.5772/intechopen.97885, ISBN 978-1-83881-121-1, retrieved 2025-05-05
- ^ Mustaev, Arkady (2023-06-21), Ameen, Sadia; Shaheer Akhtar, Mohammad; Shin, Hyung-Shik (eds.), "Inorganic Phosphate: The Backbone of Life", Functional Phosphate Materials and Their Applications, IntechOpen, doi:10.5772/intechopen.109117, ISBN 978-1-80356-800-3, retrieved 2025-05-05
- ^ Sun, Sam Z; Empie, Mark W (2012). "Fructose metabolism in humans – what isotopic tracer studies tell us". Nutrition & Metabolism. 9 (1): 89. doi:10.1186/1743-7075-9-89. ISSN 1743-7075. PMC 3533803. PMID 23031075.
- ^ a b Hannou, Sarah A.; Haslam, Danielle E.; McKeown, Nicola M.; Herman, Mark A. (2018-02-01). "Fructose metabolism and metabolic disease". Journal of Clinical Investigation. 128 (2): 545–555. doi:10.1172/JCI96702. ISSN 0021-9738. PMC 5785258. PMID 29388924.
- ^ a b c Hue, L.; Rider, M. H. (1987-07-15). "Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues". The Biochemical Journal. 245 (2): 313–324. doi:10.1042/bj2450313. ISSN 0264-6021. PMC 1148124. PMID 2822019.
- ^ Furuya, E; Yokoyama, M; Uyeda, K (January 15, 1982). "Regulation of fructose-6-phosphate 2-kinase by phosphorylation and dephosphorylation: possible mechanism for coordinated control of glycolysis and glycogenolysis". Proceedings of the National Academy of Sciences. 79 (2): 325–329. Bibcode:1982PNAS...79..325F. doi:10.1073/pnas.79.2.325. ISSN 0027-8424. PMC 345719. PMID 6281764.
- ^ Wu, Chaodong; Okar, David A.; Newgard, Christopher B.; Lange, Alex J. (2002-01-01). "Increasing fructose 2,6-bisphosphate overcomes hepatic insulin resistance of type 2 diabetes". American Journal of Physiology. Endocrinology and Metabolism. 282 (1): E38–45. doi:10.1152/ajpendo.2002.282.1.E38. ISSN 0193-1849. PMID 11739081.
- ^ Agarwal, Vishal; Das, Sambit; Kapoor, Nitin; Prusty, Binod; Das, Bijay (2024-11-21). "Dietary Fructose: A Literature Review of Current Evidence and Implications on Metabolic Health". Cureus. 16 (11): e74143. doi:10.7759/cureus.74143. ISSN 2168-8184. PMC 11663027. PMID 39712814.
- ^ Herman, Mark A.; Birnbaum, Morris J. (2021-12-07). "Molecular aspects of fructose metabolism and metabolic disease". Cell Metabolism. 33 (12): 2329–2354. doi:10.1016/j.cmet.2021.09.010. ISSN 1550-4131. PMC 8665132. PMID 34619074.
External links
[edit]- Fructosephosphates at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Pubchem - fructose-6-phosphate
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