It is curious that although glucose, fructose and galactose have identical chemical compositions, they are processed very differently by the human body, going down quite significantly different metabolic pathways controlled by different enzymes.
Glucose is metabolised via glycolysis, a pretty complex 10-step enzymatic process that involves the decomposition of glucose into pyruvate which is then oxidised by the cells for energy and ending up later mostly as CO2 and water. Glycolysis occurs constantly throughout the body and provides the main source of energy for the whole organism.
Galactose is metabolised via a specific metabolic pathway called the Leloir Pathway – this is a four-stage process using a different set of enzymes which ends up with an end molecule called glucose 6-phosphate. Depending on blood sugar levels, this end molecule is then stored as glycogen or converted back to glucose for use in glycolysis.
The slightly odd one out
Fructose deserves a special mention. As a monosaccharide, it is also a reducing sugar (ie. its chemical structure is prone to losing electrons in a process called oxidisation) and it is metabolised by a process similar to glycolysis called fructolysis.
The major differences are that fructolysis occurs almost exclusively in the liver, and a significant portion of the metabolised fructose is stored as liver fat. As such, it can be considered that fructose may be more damaging to the liver than other monosaccharides.
One other side effect of fructose is the development of leptin tolerance – an issue initially discovered in mice. As leptin is the hormone that signals to the body that it has ingested enough food and calories, it is feasible that fructose can promote overeating by limiting the effect of leptin.
There is also a study which implicates fructose in the increased incidence of gout – however, this evidence is not necessarily conclusive.
The other curious news is that fructose has a much lower Glycaemic Index (GI) than other sugars and hence may be a better sugar for ingestion by diabetics.
Why fructose is processed differently and stored so preferentially by the human body may have its origins in our evolution. While supplies of glucose and galactose can be maintained relatively constant throughout the seasons, fructose tended to be available only during times of seasonal fruit harvests.
Hence, it may have been desirable to be able to store the energy from fructose to cover for the periods when fruits are not available. This may explain why fructose inhibits leptin and allow humans to gorge on fruits – and also why fructose is so selectively metabolised with the resulting fats stored in the liver.
For Palaeolithic man, it is highly likely that such liver fats would be used up in periods when the food supply is low. However, in modern times, fruits are available all year round and to make matters worse, the widespread use of High Fructose Corn Syrup (HFCS) in commercially-produced food is potentially causing people to (seriously) overconsume fructose.
It may be interesting to learn that a very common dining custom may be influenced by fructose: the sweet dessert or syrupy fruit salad at the end of large meals.
It is quite common for restaurants to offer a fructose-rich dessert of some kind at the conclusion of large meals – this has the effect of reducing the bloated effect of overeating (due to the fructose suppression of leptin), and allows the diners to waddle off home more comfortably after a heavy meal.
And this trick still works even if the desserts are made with sucrose (cane sugar) because the body breaks sucrose down into more or less equal amounts of glucose and fructose – and to get more fructose into the body, the pastry chef just has to make the dessert extra sweet with normal sugar. So now you know.
Please don’t think that fructose is somehow a “worse” sugar compared to other sugars – the truth is that persistent overconsumption of all kinds of sugar is simply a bad idea.
Why have fat when we have glycogen?
Excess blood glucose can be converted and stored as glycogen via a process called glycogenesis – this is so that the body has a constant reserve of energy throughout the day.
After all, it is not really practical to snack all day and night, and besides, the digestive system also needs a rest.
So it is interesting why the body needs fat as well. The simple reason is that the body is not really able to store a lot of glycogen – this reserve is mainly stored in the muscles and the liver and it is not readily transportable.
For example, the glycogen around the leg muscles cannot be sent to the arm muscles – however, the liver has a mechanism which uses an enzyme called glucose-6-phosphatase which can break down its glycogen into glucose and send this into the blood stream. The reserve of glycogen in humans is quite limited, around 2,000 calories’ worth of energy, or around a day of normal activity.
So the reason for the accumulation of body fats is simply because of the limited storage of glycogen. The process of fat building starts when the body already has an adequate supply of blood glucose and detects the production of a potential excess of pyruvates during glycolysis.
In this situation, the body starts the production of a rather funky protein called fatty acid synthase (FAS). This FAS is a complex bunch of enzymes and plays a big role in lipogenesis, or the creation of fat, using the pyruvate output from the glycolysis metabolic pathway.
The processes by which pyruvate is converted into fatty acids for storage is rather too fidgety to explain here but the end result is a bunch of new fat cells to add to any existing fat cells around the liver, mammary glands, waist and any other part of the body to which such cells can attach.
The rather bad news about fat cells is that there is no theoretical limit as to the numbers that can be produced – at long as there is enough glucose in the blood and an excess of pyruvate, the body will simply create and store fat cells until it dies. It is like graft to a corrupt politician – it never ends, no matter how much money had already been embezzled.
Body fat can get reduced and utilised for energy requirements by a process called fatty acid metabolism (FAM) – in particular a catabolic process called beta-oxidation (also known as lipolysis of free fatty acids). A catabolic process is simply a metabolic pathway that decomposes molecules into smaller units so that energy may be released.
FAM usually begins when the body detects that it has a persistent blood sugar glucose shortage (perhaps as a result of dieting or exercise) and therefore needs to draw from its fat reserves.
The good news is that FAM occurs in most parts of the body, so if you really want to lose some fat, then most of your body can join in and help. The bad news is that the fat loss may not be as easily targeted as you might like, so dieting and exercise may help reduce your thighs but not necessarily your waist unless you persist for an extended length of time.
Why sweeten sugar?
Quite often I notice a rather strange ingredient in commercially-produced food and drinks. Despite already having sugar, some food items still also include artificial sweeteners. There may well be several other good reasons for this but one possible answer may be that sugar is sometimes simply not sweet enough.
There is already some anecdotal evidence that humans today have a rather sweeter tooth than previous generations – despite the abundance of low-fat and low-calorie foods, more and more people have developed a preference for sweeter and sweeter foods.
How did this come about? One explanation could be due to artificial sweeteners – these compounds are fantastically sweeter than sucrose, our normally ingested natural sugar.
A recently FDA-approved artificial sugar, advantame, is 20,000 times sweeter than table sugar – and most other artificial sweeteners range from 200 to 700 times more sweet than cane sugar, despite having practically no calories.
And if these sweeteners get heavily used in our food, then we will become conditioned to expect food and drinks to taste super-sweet – basically, very sweet food and drinks will simply become the new normal.
Developing a preference for really sweet food can have several effects. One is that the body expects a certain amount of calories from sweet food and if the calories are not present due to the use of artificial sweeteners, then it is likely that the body will want to eat more food to make up for the shortage.
Another side effect apparently happens when some artificial sweeteners are mixed with normal sugars, a not unusual combination to have on a daily basis in a modern diet.
The side-effect is that insulin levels are raised rather higher than for the amount of actual real sugar consumed – the body has responded to the artificial sweetener as if it was a real sugar.
However, the overall impact on human health of this effect has yet to be accurately determined and currently there is no firm evidence that this may be a serious health issue or a factor in the development of diabetes.
The comforting news is that, at present, there is no concrete evidence that artificial sweeteners pose any significant health risks to humans, despite their astonishing characteristics.
One other mildly funny effect is that alcohol mixed with diet drinks appears to enter the blood faster than alcohol mixed with real sugar drinks.
The explanation may be that sugary drinks cause the digestive system to retain the liquid in the stomach longer than diet drinks as the stomach needs to digest the sugars.
With diet drinks, it would appear that the alcohol passes into the blood stream with a lot less hindrance from the stomach.
Watch out for Part 3: Why the body prefers glucose