So a couple of months ago I started experimenting with a new studying style; handwriting instead of typing. I actually wrote a blog a couple of years ago about which is better, and handwriting was the winner; it was actually one of the first blogs I ever wrote and I’m as obsessed with the topic then as I am now. Yet after over two years of pre-med studies, I’ve stuck with typing. But I realized not a lot of what I’m learning is sticking and I want to fix that. So I started reading the Pearson Biochemistry book because that’s apparently what I do in my spare time, and have been handwriting notes as I go through.
I actually started with this frustration about concepts such as glycolysis; it’s a topic I’ve studied for years yet I feel I can’t truly explain it in plain language; or any language for that matter. So I went back and spent some time with glycolysis, for no other reason but my own knowledge; I actually started all the way back in my biology textbook. And I handwrote what I learned. And over the next couple of days I practiced recalling the key ideas behind glycolysis. And… I think it worked. I mean, I had to review my notes just before writing this, but most of what I recalled was there. I wanted to, for the sake of finally committing this to memory, and creating a place that I can access in case that memory lapses, talk about glycolysis.
Glyco– comes from Greek glykýs, meaning “sweet” and “lysis” means… you know, to break apart. The idea here is to break a six-carboned sugar, glucose, into two, three-carboned sugars which are called glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP) but they aren’t really important here. There is, however, a 3-carbon compound that’s very important: pyruvate.
The main goal of glycolysis is to create two molecules of pyruvate. Pyruvate is a negatively charged, conjugate base of pyruvic acid. Pyruvic acid is a cool molecule, because it’s a combination of a carboxylic acid and ketone functional group. Before I talk about what happens next to pyruvate, I want to talk about oxidation. The age-old mnemonic for me is LEO / GER, where LEO stands for “lose electron oxidation.” And this is what we do to fuel, we harvest its electrons to give us energy. And a key fuel for us are carbohydrate polysaccharides like sucrose, lactose, and starch. First, however, our digestive system must hydrolyze these polysaccharides into the monosaccharide glucose before glycolysis can begin. The chemical formula for glycolysis is glucose + oxygen to create carbon dioxide, water, and “energy.” Oxygen is the oxidizer here; it plucks electrons from glucose. Unlike an acid/base reaction (glycolysis is technically a combustion reaction), however, it’s not just an electron that is being harvested, the proton goes with it or, in other words, an entire hydrogen atom; this is sort of where all of the carbon dioxide comes from. Oxygen is electronegative because it has a large number of protons in relation to its valence electrons, giving it a nice healthy positive charge that attracts electrons like crazy. Oxygen is not only the indirect oxidizer (electron harvester) of glycolysis (NAD+ is technically the oxidizing agent of glycolysis), it’s the ultimate electron receptor at the end of oxidative phosphorylation, where we get most of our ATP.
Okay, so glycolysis occurs in the cytosol. And now that we have pyruvate, which is a product of the oxidation of glycolysis (there are a bunch of steps to get there) it enters the mitochondrion (via active transport since it’s charged) and then it’s further oxidized into a high-energy compound called acetyl coenzyme-A or acetyl CoA. To become acetyl-CoA, Pyruvate is actually oxidized this time by something called NAD+, which becomes NADH because it is picking up a hydrogen. Acetyl CoA is… massive; it has 89 atoms in total! The only resemblance to pyruvate is that it’s just the lopped off ketone part, now called an acetyl group. Okay so I mean most of acetyl CoA is coenzyme A. Enzymes are proteins; they are long chains of amino acids. We’re getting serious now. It’s acetyl CoA that then enters into the citric acid cycle.
I want to talk about whether glycolysis is an aerobic or an anaerobic process. Here’s the deal. Glycolysis will oxidize pyruvate whether oxygen is present or not. If oxygen is available, then we can continue forward into the citric acid cycle; it’s about electronegative oxygen driving the cycle and the electron transport chain. If oxygen is not available then glycolysis can continue onto fermentation, an extension of glycolysis. And here’s the crazy thing, in alcohol fermentation, pyruvate is converted to ethanol.
Let’s take a step back for a second. Under aerobic conditions, NAD+ is recycled because NADH transfers its electrons into the electron transport chain. However, in the absence of oxygen, NADH can transfer its electrons directly to pyruvate. The purpose of this is to regenerate NAD+ as an oxidizer which can then further harvest electrons; that’s fermentation. There are two types: lactic acid fermentation, and alcohol fermentation.
In alcohol fermentation, pyruvate is converted to acetaldehyde which is then reduced by NADH, regenerating NAD+, the purpose of fermentation, to ethanol. Alcohol fermentation does not occur in humans, however we certainly use this process for baking and brewing.
Lactic acid fermentation, however, does occur in humans. We use this process when oxygen is scarce, like during strenuous exercise. It’s been mistakenly thought that lactic acid build up is what causes muscle soreness, but this isn’t the case (it’s likely just the stress and trauma from tearing muscle fibers). In lactic acid fermentation, pyruvate is reduced directly by NADH to form lactate, the conjugate base of lactic acid (remember the relationship between pyruvic acid and pyruvate). Lactic acid fermentation also has non-human uses and is utilized to create cheese and yogurt.
So there you have it! I found this all very interesting. Fermentation, specifically is a process I remember hearing about and “learning” about so often but I never grasped what its purpose was. Hopefully committing this all to a blog will help me remember this all!