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Can Fatty Acids Be Converted To Glucose?

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Evolving Health: Why Can't We Convert Fat To Glucose?

As evident by many sugar-laden soda pop "potbellies" of North America, lipogenesis can obviously occur from drinking and eating too much sugar (1). Wouldnt it be just grand to reverse the process and be able to lose all that fat via gluconeogenesis? Unfortunately mammals do not have the ability to synthesize glucose from fats (1). The fact is that once glucose is converted to acetyl coA there is no method of getting back to glucose. The pyruvate dehydrogenase reaction that converts pyruvate to acetyl CoA is not reversible (1p252). Because lipid metabolism produces acetyl CoA via beta-oxidation, there can be no conversion to pyruvate or oxaloacetate that may have been used for gluconeogenesis (1p252). Further, the two carbons in the acetyl CoA molecule are lost upon entering the citric acid cycle (1p252). Thus, the acetyl CoA is used for energy (1p252). There are some fatty acids that have an odd number of carbon atoms that can be converted to glucose, but these are not common in the diet (1p253). Maybe they should be made more common. Do they taste good? 1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009. 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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