November 30, 2011
Just some casual energy storage

“My name is glycogen, short term energy source of short term energy sources:
Look on my α-1,6 glycosidic bonds, ye Mighty, and despair!”

Or something to that effect anyway. It sounded way better in my head.

Glycogen is a rather gnarly molecule which stores glucose. We absorb free, individual glucose molecules from the food we ingest, but we may not want to use all the glucose all at once - so we store some of it as glycogen. The glucose molecules can be stored as a polymer known as glycogen.

I felt compelled to share this wondrous molecule with the tumblrverse for the main reason that it has the most beautiful structure, almost fractal-like in its branching. Linear chains of glucose form the foundations of the glycogen molecules, where they are linked via α-1,4-glycosidic bonds, and the branches form from α-1,6 glycosidic bonds.

The carbons in glucose are specifically numbered, as shown above - which is where we get those names for the glycosidic bonds. Like in the diagram below!

The branched structure means we don’t need to store glucose in long linear chains which would just take up space. Might as well utilise more spatial dimensions than just one, after all. It’s a quick source of energy compared to fat as it takes a relatively simple chain of reactions from stimulus to glucose release to energy utilisation(glucagon, adrenaline etc, which indicate low blood glucose and energy expenditure respectively). Glycogen phosphorylase is an enzyme which releases a single glucose molecule from the chain, via attack of the glycosidic 1,4 bond with a phosphate. This cleaves off one glucose molecule with a phosphate attached to it, which is called glucose-1-phosphate.

Close up diagrams of the glucose chains which make up glycogen. Many of these add together to give the initial picture I started this post with.

The glucose-1-phosphate is then isomerised by an enzyme called  phosphoglucomutase to glucose-6-phosphate (which means that the phosphate group is now attached to the 6th Carbon, as opposed to the 1st Carbon as it was when initially cleaved from glycogen), and this can enter straight into the glycolytic pathway for metabolising in order to release energy. Of course, many glycogen phosphorylase molecules will be recruited at once when required, and they’ll act at the various branches to systematically cleave glucose molecules off the glycogen to release vast quantities of glucose at once (the branching of glycogen provides a large surface area for glycogen phosphorylase enzymes to act, for simulataneous large scale release of glucose).

The glucose from glycogen is an immediate, first line source of energy in this way and is used up relatively rapidly, making time for the metabolism to prepare for the sustained, high energy release of fatty acid metabolism which is what the body inevitably switches too. Metabolising a fat takes longer than metabolising glucose molecules, but it releases looooads more energy and water.

But let’s not shift the attention from glycogen here. The majority of the brain’s energy comes from free-floating glucose in the blood, which is odd because the brain is such an energy expensive organ. There’s very little, if any, metabolically active fat in the brain, reason being that there just isn’t anywhere to store it in the compact cranial space. BUT there is some glycogen, stored in a type of non-neuronal brain cell called an astrocyte (part of a group of cells known as glia (or gleeeaaaa as my Scottish glia lecturer/dissertation supervisor says it, cause he’s awesome)). When neurons are highly active, possibly in response to some kind of experience the person is having, the free glucose in the blood is just not enough to sustain the neuronal function. Enter, astrocytes and their glycogen.

Electron micrograph of astrocytes in the brain. Red arrows are pointing to glycogen granules within the astrocytes.

Astrocytes can break down their glycogen to release glucose in times of high neuronal activity. The glucose is anaerobically metabolised into lactate - which is shuttled from the astrocyte into the neuron as a portable energy source to sustain the activity of, and power the changes in the neuron that occur in response to experience-related activity - in essence, driving neuronal plasticity - or even more in-essence, driving the processes that form memories.

To further this point, experiments in rats have shown that inhibiting brain glycogen metabolism impairs long term memory formation - BUT long term memory formation can be rescued by administering extra lactate to the rats brain! One hypothesis for sleep is that it gives the brain an opportunity to replenish depleted glycogen stores, which is one reason why sleep may be so important for memory formation and cognitive function.

Glia, glycogen and glucose - some winning players in brain function.

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