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Fat To Glucose Pathway

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Pathways In The Coordination Of Cellular Glucose And Fat Metabolism

Pathways in the coordination of cellular glucose and fat metabolism Last Updated on Sat, 04 Mar 2017 | Fatty Acids The metabolism of fat and carbohydrate are closely linked; optimal oxidation of fat and conservation of glucose occur in the fed state and the opposite in the fasted state. Current theory identifies two major biochemical pathways as central components of this integrated coordination of energy metabolism . These are the glucose-fatty acid cycle first described in 1963 (Randle et al., 1963) and the malonyl CoA / carnitine palmitoyl transferase (CPT)-1 pathway which was suggested by the studies of McGarry and coworkers in the late 1970s (McGarry et al., 1977). Importantly, these two pathways complement each other (Fig. 2.1). The glucose- fatty acid cycle links carbohydrate and fat metabolism and was one of the first theories to describe how fatty acids influence glucose metabolism . It centres on the proposition that increased beta-oxidation (utilisation) of fatty acids in skeletal muscle results in a reduced uptake and oxidation of glucose (Fig. 2.1), offering additional fine-tuning to the 'coarse' control of glucose and fat utilisation that is enforced at whole body le Continue reading >>

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  1. manohman

    Why can't fat be converted into Glucose?

    So the reason cited is that beta oxidation/metabolism of fats leads to formation of acetyl coa, a 2 carbon molecule, and that because of that it cannot be converted back into glucose.
    Why exactly is that the case?
    If Glucogenic amino acids can be converted into citric acid cycle intermediates and then turn back into glucose via gluconeogensis, then why cant Fatty Acids which yield Acetyl Coa. Can't you just have Acetyl Coa enter the citric acid cycle and produce the same intermediates that the glucogenic amino acids creat?

  2. Czarcasm

    manohman said: ↑
    So the reason cited is that beta oxidation/metabolism of fats leads to formation of acetyl coa, a 2 carbon molecule, and that because of that it cannot be converted back into glucose.
    Why exactly is that the case?
    If Glucogenic amino acids can be converted into citric acid cycle intermediates and then turn back into glucose via gluconeogensis, then why cant Fatty Acids which yield Acetyl Coa. Can't you just have Acetyl Coa enter the citric acid cycle and produce the same intermediates that the glucogenic amino acids creat?
    Click to expand... Both glucose and fatty acids can be stored in the body as either glycogen for glucose (stored mainly in the liver or skeletal cells) or for FA's, as triacylglycerides (stored in adipose cells). We cannot store excess protein. It's either used to make other proteins, or flushed out of the body if in excess; that's generally the case but we try to make use of some of that energy instead of throwing it all away.
    When a person is deprived of nutrition for a period of time and glycogen stores are depleted, the body will immediately seek out alternative energy sources. Fats (stored for use) are the first priority over protein (which requires the breakdown of tissues such as muscle). We can mobilize these FA's to the liver and convert them to Acetyl-CoA to be used in the TCA cycle and generate much needed energy. On the contrary, when a person eats in excess (a fatty meal high in protein), it's more efficient to store fatty acids as TAG's over glycogen simply because glycogen is extremely hydrophilic and attracts excess water weight; fatty acids are largely stored anhydrously and so you essentially get more bang for your buck. This is evolutionary significant and why birds are able to stay light weight but fly for periods at a time, or why bears are able to hibernate for months at a time. Proteins on the other hand may be used anabolically to build up active tissues (such as when your working out those muscles), unless you live a sedentary lifestyle (less anabolism and therefore, less use of the proteins). As part of the excretion process, protein must be broken down to urea to avoid toxic ammonia and in doing so, the Liver can extract some of that usable energy for storage as glycogen.
    Also, it is worth noting that it is indeed possible to convert FA's to glucose but the pathway can be a little complex and so in terms of energy storage, is not very efficient. The process involves converting Acetyl-CoA to Acetone (transported out of mitochondria to cytosol) where it's converted to Pyruvate which can then be used in the Gluconeogenesis pathway to make Glucose and eventually stored as Glycogen. Have a look for yourself if your interested: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002116.g003/originalimage (and this excludes the whole glycogenesis pathway, which hasn't even begun yet).
    TLDR: it's because proteins have no ability to be stored in the body, but we can convert them to glycogen for storage during the breakdown process for excretion. Also, in terms of energy, it's a more efficient process than converting FA's to glycogen for storage.

  3. soccerman93

    This is where biochem comes in handy. Czarcasm gives a really good in depth answer, but a simpler approach is to count carbons. The first step of gluconeogenesis(formation of glucose) requires pyruvate, a 3 carbon molecule. Acetyl Co-A is a 2 carbon molecule, and most animals lack the enzymes (malate synthase and isocitrate lyase) required to convert acetyl co-A into a 3 carbon molecule suitable for the gluconeogenesis pathway. The ketogenic pathway is not efficient, as czarcasm pointed out. While acetyl co-A can indeed be used to form citric acid intermediates, these intermediates will be used in forming ATP, not glucose. Fatty acid oxidation does not yield suitable amounts of pyruvate, which is required for gluconeogenesis. This is part of why losing weight is fairly difficult for those that are overweight, we can't efficiently directly convert fat to glucose, which we need a fairly constant supply of. Sorry, that got a little long-winded

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What Is Gluconeogenesis? How Does Does It Control Blood Sugars?

What is gluconeogenesis? How does does it control blood sugars? by breaknutrition | Sep 12, 2017 | Ketogenic Diets | 8 comments Step into the low-carb world and soon enough youll hear the term GlucoNeoGenesis. GNG for short, is your bodys ability to construct glucose, a kind of sugar, out of molecules that arent glucose. It does this to ensure that, if you dont eat any carbs, the cells in your body that need glucose will still get enough of it. Its one reason why humans are so good at fasting or delaying death from starvation for weeks or months. We can meet our own need for glucose by producing it ourselves. What do I mean by cells in your body that need glucose? I mean a reliance on glucose to accomplish its basic physiological tasks over a long time maybe a lifetime. You then might ask, but is there a difference when meeting your glucose needs with GNG versus by eating carbs? Fair question. You could also ask although no one seems to is it better to meet your glucose needs through GNG than by eating carbs? Also a fair question I think but one people will most likely scoff at. These questions deserve more space than Im according them here, so theyll have to be wrestled with in a Continue reading >>

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Popular Questions

  1. manohman

    Why can't fat be converted into Glucose?

    So the reason cited is that beta oxidation/metabolism of fats leads to formation of acetyl coa, a 2 carbon molecule, and that because of that it cannot be converted back into glucose.
    Why exactly is that the case?
    If Glucogenic amino acids can be converted into citric acid cycle intermediates and then turn back into glucose via gluconeogensis, then why cant Fatty Acids which yield Acetyl Coa. Can't you just have Acetyl Coa enter the citric acid cycle and produce the same intermediates that the glucogenic amino acids creat?

  2. Czarcasm

    manohman said: ↑
    So the reason cited is that beta oxidation/metabolism of fats leads to formation of acetyl coa, a 2 carbon molecule, and that because of that it cannot be converted back into glucose.
    Why exactly is that the case?
    If Glucogenic amino acids can be converted into citric acid cycle intermediates and then turn back into glucose via gluconeogensis, then why cant Fatty Acids which yield Acetyl Coa. Can't you just have Acetyl Coa enter the citric acid cycle and produce the same intermediates that the glucogenic amino acids creat?
    Click to expand... Both glucose and fatty acids can be stored in the body as either glycogen for glucose (stored mainly in the liver or skeletal cells) or for FA's, as triacylglycerides (stored in adipose cells). We cannot store excess protein. It's either used to make other proteins, or flushed out of the body if in excess; that's generally the case but we try to make use of some of that energy instead of throwing it all away.
    When a person is deprived of nutrition for a period of time and glycogen stores are depleted, the body will immediately seek out alternative energy sources. Fats (stored for use) are the first priority over protein (which requires the breakdown of tissues such as muscle). We can mobilize these FA's to the liver and convert them to Acetyl-CoA to be used in the TCA cycle and generate much needed energy. On the contrary, when a person eats in excess (a fatty meal high in protein), it's more efficient to store fatty acids as TAG's over glycogen simply because glycogen is extremely hydrophilic and attracts excess water weight; fatty acids are largely stored anhydrously and so you essentially get more bang for your buck. This is evolutionary significant and why birds are able to stay light weight but fly for periods at a time, or why bears are able to hibernate for months at a time. Proteins on the other hand may be used anabolically to build up active tissues (such as when your working out those muscles), unless you live a sedentary lifestyle (less anabolism and therefore, less use of the proteins). As part of the excretion process, protein must be broken down to urea to avoid toxic ammonia and in doing so, the Liver can extract some of that usable energy for storage as glycogen.
    Also, it is worth noting that it is indeed possible to convert FA's to glucose but the pathway can be a little complex and so in terms of energy storage, is not very efficient. The process involves converting Acetyl-CoA to Acetone (transported out of mitochondria to cytosol) where it's converted to Pyruvate which can then be used in the Gluconeogenesis pathway to make Glucose and eventually stored as Glycogen. Have a look for yourself if your interested: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002116.g003/originalimage (and this excludes the whole glycogenesis pathway, which hasn't even begun yet).
    TLDR: it's because proteins have no ability to be stored in the body, but we can convert them to glycogen for storage during the breakdown process for excretion. Also, in terms of energy, it's a more efficient process than converting FA's to glycogen for storage.

  3. soccerman93

    This is where biochem comes in handy. Czarcasm gives a really good in depth answer, but a simpler approach is to count carbons. The first step of gluconeogenesis(formation of glucose) requires pyruvate, a 3 carbon molecule. Acetyl Co-A is a 2 carbon molecule, and most animals lack the enzymes (malate synthase and isocitrate lyase) required to convert acetyl co-A into a 3 carbon molecule suitable for the gluconeogenesis pathway. The ketogenic pathway is not efficient, as czarcasm pointed out. While acetyl co-A can indeed be used to form citric acid intermediates, these intermediates will be used in forming ATP, not glucose. Fatty acid oxidation does not yield suitable amounts of pyruvate, which is required for gluconeogenesis. This is part of why losing weight is fairly difficult for those that are overweight, we can't efficiently directly convert fat to glucose, which we need a fairly constant supply of. Sorry, that got a little long-winded

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Gluconeogenesis - An Overview | Sciencedirect Topics

Gluconeogenesis is the process that leads to the generation of glucose from a variety of sources such as pyruvate, lactate, glycerol, and certain amino acids. Larry R. Engelking, in Textbook of Veterinary Physiological Chemistry (Third Edition) , 2015 Gluconeogenesis occurs in the liver and kidneys. Gluconeogenesis supplies the needs for plasma glucose between meals. Gluconeogenesis is stimulated by the diabetogenic hormones (glucagon, growth hormone, epinephrine, and cortisol). Gluconeogenic substrates include glycerol, lactate, propionate, and certain amino acids. PEP carboxykinase catalyzes the rate-limiting reaction in gluconeogenesis. The dicarboxylic acid shuttle moves hydrocarbons from pyruvate to PEP in gluconeogenesis. Gluconeogenesis is a continual process in carnivores and ruminant animals, therefore they have little need to store glycogen in their liver cells. Of the amino acids transported to liver from muscle during exercise and starvation, Ala predominates. b-Aminoisobutyrate, generated from pyrimidine degradation, is a (minor) gluconeogenic substrate. N.V. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry , 2011 Gluconeogenesis refers to synthesis of ne Continue reading >>

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Popular Questions

  1. Christian

    I read conflicting views about whether or not the human body can create glucose out of fat. Can it?

  2. David

    Only about 5–6% of triglyceride (fat) can be converted to glucose in humans.
    This is because triglyceride is made up of one 3-carbon glycerol molecule and three 16- or 18-carbon fatty acids. The glycerol (3/51-to-57 = 5.2–5.9%) can be converted to glucose in the liver by gluconeogenesis (after conversion to dihydroxyacetone phosphate).
    The fatty acid chains, however, are oxidized to acetyl-CoA, which cannot be converted to glucose in humans. Acetyl-CoA is a source of ATP when oxidized in the tricarboxylic acid cycle, but the carbon goes to carbon dioxide. (The molecule of oxaloacetate produced in the cycle only balances the one acetyl-CoA condenses with to enter the cycle, and so cannot be tapped off to gluconeogenesis.)
    So triglyceride is a poor source of glucose in starvation, and that is not its primary function. Some Acetyl-CoA is converted to ketone bodies (acetoacetate and β-hydroxybutyrate) in starvation, which can replace part — but not all — of the brain’s requirement for glucose.
    Plants and some bacteria can convert fatty acids to glucose because they possess the glyoxylate shunt enzymes that allow two molecules of Acetyl-CoA to be converted into malate and then oxaloacetate. This is generally lacking in mammals, although it has been reported in hibernating animals (thanks to @Roland for the last piece of info).

  3. blu potatos

    To be more detailed it is the irreversibly of the reaction carried by Pyruvate dehydrogenase that makes the conversion of the fatty acid chains to glucose impossible. The fatty acids chains are converted to acetyl-CoA.
    Acetyl-CoA to be converted into pyruvate need an enzyme that can do the Pyruvate Dehydrogenase's inverse reaction (in humans there is no such enzyme). Than the pyruvete inside the mitochondria is converted into glucose(gluconeogenesis).

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