Fructose and Galactose Metabolism and carbohydrate metabolism in tissues P d phosphorylated Pase Phosphatase With fructose and galactose once consumed we will be using them as energy or convert them to glucose Once we have glucose we can go through glycolysis for energy or glucose can be used to regulate blood glucose levels This part is going to be short answer The liver is going to be the major site for Fructose and Galactose metabolism Why We have Hexokinase in all cells of our body which is always saturated with Glucose It can metabolize Fructose and Galactose Hexokinase has a low KM for glucose high affinity but has a high KM for Fructose and Galactose low affinity Since Hexokinase is saturated at all times we will have to have different enzymes acting upon those substrates Those enzymes are found in the liver Hexokinase is the first step for the metabolism of fructose while Galactokinase is responsible for catalyzing the first step in Galactose metabolism Both Fructokinase and Galactokinase have low KM for Fructose and Galactose respectively So once these two are consumed they go through the circulation to the liver where the first metabolism step occurs Question will probably be on KM and you will have to explain all the enzymes Pretty much everything I just wrote First one we will look at is the fructose metabolism The purpose of a kinase is to add a P So we know that phosphorylation is what will be happening to those two substrates once they enter the liver Fructose will be P d on carbon one with Fructokinase to form F1P This needs an ATP to rip the phosphate from so we also form an ADP The second step has F1P ADP being broken down into two Trioses using Aldolase B The two Trioses are DHAP and Glyceraldehyde which is similar to the breakdown of F1 6BP to DHAP and G3P in glycolysis Anyway these two trioses can go through glycolysis and gluconeogenesis Glyceraldehyde has to be converted into G3P first This is done by using an ATP and Glyceraldehyde kinase Triokinase and then can go into glycolysis DHAP can enter glycolysis directly We can also have those two enter gluconeogenesis Now we have Aldolase A being used for Glyceraldehyde this is possible because it is a reverse reaction so we can use the same enzyme The A or B just suggests differentiation between the pathways in which the enzyme is being used She said really pay attention and take notes on this What is the rate limiting step in glycolysis The one catalyzing it is PFKI which is the rat controlling enzyme The Trioses are entering glycolysis after the PFKI step This means that it is past the rate controlling enzyme So if we have a lot of Fructose it will decrease the rate of glycolysis but actually increase It is increased because it enters past the controlling step so without rate control your rate of glycolysis increases Pyruvate is the product of glycolysis and it goes to Acetyl CoA after So if you increase the amount of Pyruvate and Acetyl CoA you are forming you are also increasing FA synthesis And remember that all the excess of nutrients in our body will be stored in our body will be stored at fat in adipose tissue So if you are storing the FA in what form are they being stored TG This then leads to an increase in esterification The process of combining the FA with the G3P is called esterification Increased TG synthesis increases VLDL VLDL is responsible for carrying TG in our body which raises serum TG Once those TG are delivered to some tissues VLDL becomes LDL in your bloodstream LDL delivers cholesterol to tissues in our body that has receptors for LDL This increases serum cholesterol This can cause increased risk of heart disease She kind of skipped already discussed this slide in talking about the other stuff We can have deficiencies of some enzymes specifically a lack of Fructokinase This can lead to Fructosemia or Essential Fructosuria Fructosuria meaning decreased amount of Fructose in your urine Fructose Intolerance is hereditary and is the lack of Aldolase If we don t have Aldolase we can phosphorylate Fructose because we have Fructokinase but now you don t have Aldolase to break down F1 6BP to Trioses This is resulting in hypoglycemia So if you don t have that enzyme to metabolize that you are probably wondering why you are ending up with hypoglycemia then if we still have glycogen stores in the liver which we can break down to glucose Well what happens is F1P is a negative allosteric inhibitor for Glycogen Phosphorylase so a buildup of F1P will actually inhibit Glycogen Phosphorylase so we won t be able to break down glycogen to glucose for regulation of blood glucose levels Now we are going onto Galactose metabolism Galactokinase will phosphorylate Galactose to Galactose 1P with the use of an ATP Our second step is a little like glycogen metabolism Your Galactose 1P is going to go to UDP galactose In order to do that it will require UDP Glucose Galactose 1P Uridyl Transferase will transfer a P to the glucose in the UDP glucose forming Glucose 1P as the UDP is transferred to the Galactose forming UDP Galactose Now you have your UDP Galactose This will be converted to UDP glucose by UDP Galactose 4 Epimerase in a reversible reaction From UDP Glucose you can have Glycogen Synthase form Glycogen Galactose is not an essential nutrient so if you figure out you are Lactose intolerant it is because you have low activity or lack the enzyme of Lactase Lactase s purpose is to break down Lactose into Glucose and Galactose Even though people who find this out need to go on lactose free diets you would think that they don t have galactose but our body can form lactose but how By lactose synthase The two things you would need are Glucose and Galactose You would get UDP Galactose through this reaction Glycogen will break down to G1P then that Glucose can be activated with UDP to get UDP Glucose This is converted to UDP Galactose it combines with Glucose to form Lactose If you have Glycogen it can go through glycogenolysis Glycogen will be converted to G1P with Glycogen Phosphorylase Then G1P will be converted to G6P with Phosphoglucomutase G6P then is converted to Glucose with G6Pase UDP glucose can feedback to supply substrate in Galactose metabolism As we saw Galactose 1P is converted to UDP Galactose and UDP Galactose is converted to UDP Glucose That UDP Glucose is shuttled back and reused in the first reaction from Galactose 1P to UDP Galactose This will make the process go a little faster rather than
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