I think biochemistry is pretty sweet, but how “sweet”’s your blood after you eat? For people with diabetes, that’s something they might need to measure, and teaching you the science behind it would be my pleasure! The ability of glucose to reduce allows glucometers to deduce, the concentration of sugar after you drink juice, helping diabetics know how much insulin to infuse!
Insulin is a hormone (chemical messenger) your body uses to help control blood sugar levels. I’m grateful that I don’t have diabetes, but, for people who do, their body has a hard time making and/or “hearing” insulin’s call to “let glucose in!” As a result, they have trouble controlling blood sugar levels, so they often use devices called glucometers to measure blood glucose levels.
Diabetes is a disease where the body either doesn’t make (type 1 diabetes (T1D)) or can’t use effectively (type 2 diabetes (T2D)) a hormone called insulin. Hormones are chemical messengers that can relay messages throughout & between cells in your body. Different hormones are made of different building blocks & relay different messages.
Insulin is a peptide hormone, so it’s made up of amino acids (these are the same “letters” as proteins us but proteins are more like novels while peptide hormones are like “text messages”). The text sender is an organ called the pancreas, & the message it relays is – there’s a lot of sugar in the blood – let’s take some into the cells, use some, & store some, why don’t we?
The pancreas basically sends out a “mass text” to cells throughout the body in the form of insulin. The cells respond by opening their doors to glucose (the main monosaccharide (single sugar unit)), importing it from the bloodstream into the cells thus lowering the amount of glucose in the blood. Since glucose is hydrophilic (water-loving), it needs help getting through the hydrophobic, fatty membranes surrounding a cell. Help is provided via specialized transporter proteins that provide a channel through. These transporters are stored in membrane-bound vesicles inside the cell – when the cell gets insulin’s message (by insulin binding to receptors on the cell surface), those vesicles fuse with the outer membrane, inserting these transporters into it and thus providing a path in.
Additionally, insulin tells cells in the liver to “turn on” an enzyme called glycogen synthase, which strings excess glucose into chains (polysaccharides) called glycogen for storage. more on glycogen here: http://bit.ly/2JwIuRV
Too much sugar is hypERglycemia (remember ovER). Too little sugar is hyPOglycemia (remember below). Both are bad. Which is why having a properly-functioning “early alert” system through insulin signaling is so important. It gives your cells time to prepare & avert a crisis.
But T1D is like the text message never being sent and T2D is like the text gets sent but the phones have the caller on their block list so they never hear the message. If cells are phones, it’s not that they’re completely turned off – they can still get other messages fine, but their bodies have become “desensitized” to it.
Without a functional natural “early alert” system, diabetics need an “unnatural” way to measure how much glucose is in their blood and, if appropriate, inject/infuse insulin (if sugar’s too high) or eat some sugar if it’s too low. But in order to know what, if any, correcting is required, you need to know what your blood sugar level currently is.
And common ways to do this take advantage of glucose’s ability to act as a reducing agent. Molecules interact through their electrons (negatively-charged subatomic particles that whizz around the atoms’ positively-charged nucleus). Reduction and oxidation (redox) are just fancy terms to describe the movement of electrons between them.
You can remember which is which with OIL RIG: Oxidation Is Loss (of electrons) and Reduction is Gain (of electrons). Much more here: http://bit.ly/2XBhNUQ
Reducing agents are agents of reduction – they cause something to be reduced and are oxidized in the process. So in order to serve as a reducing agent, a molecule has to be able to be willing and able to give up an electron(s), reducing the thing it gives it to and getting oxidized in the process.
Since glucose is a reducing agent, it will donate electrons, and if we can measure how many electrons are getting transferred – either directly (electron movement is current so you can measure current produced) or indirectly (e.g. transfer them from something that changes color upon losing them) – we can figure out how much glucose there is. The former is the rationale behind the glucose monitors diabetics often use (glucometers) whereas the latter is commonly utilized in organic chemistry labs with the color-changer being a metal in tests like Benedict’s test.
So how do they work? What makes glucose reducing? We talked about what insulin is, but what’s glucose? Glucose is a sugar and it’s one of the “monosaccharide” “building blocks” of carbohydrates. Sugars are basically really alcoholic hydrocarbons. An alcohol is just a hydroxyl (-OH) group and sugars have about 1 of these for every carbon. Sugars also have (or at least have under certain conditions) a carbonyl group, which is a C=O. Where’s the carbonyl?
In ketones (present in ketoses) it’s monKEy in the middle – > the carbonyl is sandwiched between carbons. Whereas an aldehyde (present in aldoses like glucose) is “AL Done” -> the carbonyl is at the end – there’s just a hydrogen on the other side.
H is kinda like a dead end in that it can only form 1 bond, so you can’t connect it to 2 things. So if you stick an H after something you might thing chain’s gotta stop there right? Well, here’s were another special thing about H comes in – the bonds it does form aren’t very strong because, with only a single proton, it doesn’t have much in the way of pulling power.
This is especially noticeable in the case of hydroxyl groups. O is much more electron-hogging (electronegative) than H so it pulls the electrons they share away from the hydrogen, so the hydrogen’s proton can leave as a proton (H+) leaving that electron behind, thus making the O negative. Then that O seeks out something positive (or at least partly positive). And, without that H it can link up to something like O or C that does allow for linking – so turns out H was more of a “temporary cap” than a true dead end!
C is more of a fair sharer when it comes to C-H bonds – usually… But in an aldehyde the C is having electrons pulled away from it by the O, so it’s harder for it to share with the H – in fact, the O is so hoggy that the C is partly positive. So it’s vulnerable to attack by things like that O-.
Since monosaccharides have both hydroxyls (which can be made attacky O- ) and a carbonyl, one of the -OH legs can attack the carbonyl carbon, which we call the anomeric carbon, ring-ifying it. In more sciencey terms, the hydroxyl combines with the aldehyde in a condensation reaction, forming something called a hemiacetal ring structure.
Depending on which direction the carbonyl gets attacked from, the first group can stick up or down from the ring and these are different “stereoisomomers” (β or α). But this reaction’s reversible, so it can keep going back and forth, opening & closing (and potentially switching between β & α in the process (mutarotation)
How does this help us measure glucose?? Only the open form is oxidizable (the aldehyde gets oxidized to a carboxylic acid, “swapping out an H for an OH, turning -(C=O)-H into -(C=O)-OH). Only ~1% of glucose is in the open-chain form at any one time, but, if there’s an oxidizing agent willing to take the electrons, that 1% is enough for reduction to occur. And remember, redox reactions involve electron transfer, which we have ways to measure!
There are several colorimetric tests (something happening makes something change color) you can use to measure reducing sugars like glucose. The basic idea is, get a metal to accept electrons from glucose, oxidizing it from an aldehyde to a carboxylate. When the metal gains the electrons, it changes its structure a bit, so it now absorbs a different wavelength of light. If there aren’t reducing sugars* there’s nothing donating, so the metal has nothing to accept, so the metal stays the same color. But if there are reducing sugars* then the metal will get reduced by them and change color.
I used asterisks because these tests, are basically testing how much reducing agent there is, whatever the source. So reduction might be coming from glucose but it could be coming from a bunch of other stuff as well.
If we want to measure glucose and only glucose, we need something with more specificity. Biochemistry to the rescue! When your body needs to facilitate a reaction & needs high specificity it often turns to molecules called enzymes. Usually these are proteins, sometimes RNA, sometimes both. They are designed to specifically recognize things that need working on (substrates) (and by this I don’t mean they can go “oh hey, it’s bob!” more that they just have shape/charge etc. so that if they bump into bob he’ll stick around, but if they bump into joe they’ll clash).
Glucose test strips have a bunch of layers with space between them for blood to get sucked into. One of those layers is coated with an enzyme called glucose oxidase that’s specific for glucose (it’ll “clash” with other sugars, even if they’re reducing sugars). When you stick a drop of blood on a glucose test strip, glucose lives up to its title as a reducing sugar and does some reducing. With the help of glucose oxidase (GOx) (or glucose dehydrogenase (GDH) in some newer ones), it gives up electrons and takes an O, becoming oxidized to gluconic acid.
By definition, an enzyme speeds up (catalyzes) a reaction without getting used up in the process (it’s a renewable resource). So, by definition, an enzyme can’t keep what it gets or it wouldn’t be able to do it again. So GOx gives the electrons to something else. In it’s normal role, GOx gives them to water & oxygen which take it to make hydrogen peroxide
In a glucose test strip, instead of oxygen, there’s a “mediator” – often a metal complex like potassium ferricyanide, [K3Fe(CN)6] (aka Prussian red) waiting to accept the electrons. Each mediator molecule can accept an electron, making it ferrocyanide. And then each mediator “ships” the electron to a + charged electrode. Moving electrons is electricity, so you generate an electric current. And this is what gets measured. The more glucose there is, the more electrons can be given up and therefore the greater the current and the greater the signal. Then the computer in the glucometer converts that measurement of current into a measurement of glucose.
This is for self-monitoring blood glucose (SMBG) meters: test strips + small blood sample (e.g. finger stick). But there are also continuous glucose monitors (CGMs): sensor implanted under skin – takes readings every few minutes. And a lot of work’s being done on noninvasive glucometers: the future of monitoring? no blood required = measure through skin
more on insulin: http://bit.ly/insulindiabetes