1. Contact me at kgahern@davincipress.com / Friend me on Facebook (kevin.g.ahern) 2. Download my free biochemistry book at http://biochem.science.oregonstate.edu/biochemistry-free-and-easy 3. Take my free iTunes U course at https://itunes.apple.com/us/course/biochemistry/id556410409 4. Check out my free book for pre-meds at http://biochem.science.oregonstate.edu/biochemistry-free-and-easy 5. Lecturio videos for medical students - https://www.lecturio.com/medical-courses/biochemistry.course 6. Course video channel at http://www.youtube.com/user/oharow/videos?view=1 7. Check out all of my free workshops at http://oregonstate.edu/dept/biochem/ahern/123.html 8. Check out my Metabolic Melodies at http://www.davincipress.com/ 9. My courses can be taken for credit (wherever you live) via OSU's ecampus. For details, see http://ecampus.oregonstate.edu/soc/ecatalog/ecourselist.htm?termcode=all&subject;=BB 10. Course materials at http://oregonstate.edu/instruct/bb450 Glycolysis II/III 1. Other sugars than glucose can be metabolized by glycolysis, if they are converted to intermediates of glycolysis. 2. Entry of fructose to the glycolysis cycle may be problematic in some cases. Fructose can be converted to F6P by hexokinase. Fructose can also be converted to fructose-1-phosphate (F1P) by fructokinase. Conversion of F1P to glyceraldehyde and DHAP allows fructose to be metabolized by glycolysis without being controlled by PFK. Ingestion of a lot of fructose (via high fructose corn syrup in many foods) may be a factor in obesity. 3. Galactose can enter glycolysis by being converted to galactose-1phosphate followed by converstion (ultimately) to glucose-1-phosphate and subsequently to glucose-6-phosphate, which is a glycolysis intermediate. 4. Deficiency of galactose conversion enzymes results in accumulation of galactose (from breakdown of lactose). Excess galactose is converted to galactitol (a sugar alcohol). Galactitol in the human eye lens causes it to absorb water and this may be a factor in formation of cataracts. 5. Deficiency of the enzyme lactase leads to lactose intolerance. 6. Regulation of glycolysis is controlled by three enzymes - hexokinase, PFK, and pyruvate kinase. Hexokinase's regulation is a bit complicated and is controlled partly by accumulation of product. 7. PFK is very unusual in being negatively regulated by a molecule (ATP) that is also a substrate. This is possible because the enzyme has an allosteric binding site for ATP in addition to the substrate binding site and the Km for the allosteric site is higher than the substrate binding site.PFK is also regulated by fructose 2,6 bisphosphate (F2,6BP), which strongly activates the enzyme at low concentrations. 8. Pyruvate kinase is regulated both allosterically and by covalent modification (phosphorylation/dephosphorylation). Phosphorylation of the enzyme by a protein kinase turns the enzyme activity down, whereas F1,6BP acts as an allosteric activator. This activation is known as feedforward activation. 9. Hypoxia refers to the condition where cells are short of oxygen. Since oxygen is necessary for maximum energy production from glucose, they must respond to this condition. One way they respond is by making a transcription factor known as Hypoxia Induction Factor 1 (HIF-1). HIF-1 activates transcription of genes involved in glucose transport and glycolysis. Cancer cells are frequently hypoxic and induce HIF-1, as well. Another way cancer cells battle hypoxia is to stimulate the growth of blood vessels to them by making another factor known as angiogenin. Blocking HIF-1 and angiogenin are anti-cancer therapies. 10. Gluconeogenesis accomplishes the reverse of glycolysis - synthesis of glucose from pyruvate using four different enzymes to replace three energetically unfavorable reactions in glycolysis. 11. Gluconeogenesis does not occur in all tissues of the body. The primary gluconeogenic organs of the body are the liver and part of the kidney. 12. The enzymes unique to gluconeogenesis Pyruvate Carboxylase and PEP carboxykinase (PEPCK) instead of Pyruvate Kinase of glycolysis, Fructose 1,6 Bisphosphatase (F1,6BPase) instead of Phosphofructokinase (PFK) from glycolysis, and Glucose-6-phosphatase (G6Pase) instead of Hexokinase from glycolysis. 13. F1,6BPase and G6Pase act by similar mechanisms, clipping a phosphate from their substrates and thus avoiding synthesis of ATP, which is what would be required if the glycolysis reactions were simply reversed. 14. One reaction of gluconeogenesis occurs in the mitochondrion. It is catalyzed by pyruvate carboxylase and yields the four carbon intermediate, oxaloacetate. The carboxyl group is added in forming oxaloacetate thanks to the coenzyme biotin, which carries carbon dioxide for attachment. The remaining reactions all occur in the cytoplasm, except for the G6Pase reaction, which occurs in the lumen of the endoplasmic reticulum.

• published: 25 Nov 2014
• views: 4182