Okay, after a little while, I am checking back in my blog. I hope you have been taking good notes in class on your own in the meantime. In this article, I will go over the stuff we talked about earlier this week. I covered metabolism. As I told you, this is a big topic – the stuff that complicated biochemistry courses are made of. However, we are going to look at things at a high level. We are flying over the forest at 30,000 feet. Think ‘big picture’.
What is metabolism?
Metabolism is a word you might have heard before. I am told I am skinny because my body has a high metabolic rate. Someone may have said that to you too. What they are saying is that I,…or you, burn energy fast. This is true of some people and not of others. We burn food at different rates which may affect how efficiently we gain or lose weight. That’s a subject for another time though. Metabolism is really all the biochemical reactions that take place in your body, and there are lots..LOTS of them. When all your metabolism stops, guess what? Yeah….. you’re dead.
The two categories of metabolism you should know are anabolism and catabolism. Anabolic metabolism pathways are those in which your body is making things, e.g. taking glucose and making glycogen for energy storage. Catabolism is when the body is breaking down things. For example, taking glycogen and breaking it down to glucose so that we can have energy when we need it.
Steps in Energy Metabolism
The purpose of eating is to gain energy. We get energy from a pathway that involves glycolysis, the tricarboxylic acid (TCA) cycle (also known as the citric acid and Kreb cycle), and the electron transport chain. Where are these things happening? Glycolysis occurs in the cytoplasm of the cell. That’s the inside of the cell where all the organelles hang. the TCA cycle and the electron transport chain happen in the mitochondria. You may remember from high school biology that the mitochondria are the “powerhouse of the cell”. That’s because that’s where most of the energy that we make comes from.
Regulation of Pathways
Just like how we need stoplights, stop signs, and traffic police officers to direct traffic on the road, metabolic pathways (like roads) need to be regulated. We control them using hormones and enzymes. For example, when we eat a meal, insulin is secreted, which binds to a receptor on our tissue cells. This opens a door (a certain protein) at another location on the cell called GLUT4. When GLUT4 is open, glucose flows into the cell. We have already talked extensively about enzymes so you know how important they are. For example, when we drink alcohol, we depend on alcohol dehydrogenase to break down ethanol to acetoacetate and then another called acetoacetate dehydrogenase to convert acetoacetate to acetate.
ATP – The Energy Currency of the Cell
So, as I said, the reason why we eat is to get energy. But what does energy look like? Well, you can’t really see it, just like how you can’t see electricity but know it’s there. In the cell, chemical energy is bound up in a molecule called ATP which stands for adenosine triphosphate. It is a high-energy molecule consisting of 3 phosphate groups attached to it. When the phosphate is broken…POWWWW!!!!…..you get a release of energy that can be used for work in the cell. As I illustrated in class, think of an elastic band stretched to the max. Now take a scissor and cut it. What do you think will happen? Better not hold on to it, because it’s gonna sting. The cutting of the elastic is like what happens when a phosphate bond in ATP is cut – it releases energy – lots… LOTS of it!
Let’s go ahead now and talk about the steps in the energy-producing pathway.
Glyco-lysis – what does this mean? What does it sound like? ‘Lysis’ means to break, and ‘glyco’ refers to glucose. So in glycolysis, glucose is what is being broken down. By the way, is this a catabolic or anabolic pathway? That’s right, it is catabolic since we are breaking down glucose.
The goal of glycolysis is to take glucose and convert it to two units of another molecule called pyruvate. The process takes a number of steps, each requiring a different enzyme. But, remember we are flying above the forest at 30,000 feet. As your pilot, I may need to take a slight dip to get you closer to something in the forest canopy, but otherwise, we are pretty much staying up in the clouds.
In order to make the two pyruvates, two ATP are invested in the process. Hey, you have to put in money to make money. Right? Yeah, that’s how glycolysis works. Aint gonna get nothing if you don’t put in something. We put in 2 ATP, but in the end, we made 4. That’s a profit of 2 ATP. Cool! You will also notice that glycolysis produces two molecules of NADH (Nicotinamide Adenine Dinucleotide + Hydrogen). When you see NADH think Chi-Ching!! You are making money (well…energy in our case). That’s because later down the line we can “cash out” NADH for ATP. They go for an “exchange rate” of 1 NADH to 2.5 ATP.
Aerobic and Anaerobic Pathways
OK. So we have made 2 pyruvates. What’s next? The next step is typically the TCA cycle. This step is part of an aerobic pathway since it is oxygen-dependent. But, what happens when there isn’t enough oxygen? Let’s say for example you are running a marathon. You have been pacing yourself for the last hour but now you are feeling extremely tired and your leg muscles are starting to burn. What’s happening is that your muscles are becoming oxygen-depleted. As a result, pyruvate is converted to an acid called lactate which is responsible for that burning sensation. The conversion of pyruvate to lactate is an alternate anaerobic pathway that the body switches to in order to keep supplying a bit more energy to keep you in the race. Otherwise, you would just stop, unable to finish at all. Lactate migrates from your tissues to the liver where it is converted to glucose to supply you with the energy you need.
Let’s talk about the aerobic pathway.
Pyruvate to Acetyl CoA
In the aerobic pathway, the first step is the conversion of pyruvate to acetyl Co-enzyme A (Acetyl CoA for short). At this step, carbon dioxide is produced. Not surprising that we make carbon dioxide during energy production. Right? That’s what we breathe out. Also, we produce 2 NADH. When you see NADH, what do you say? CHI-CHING!!. More money (ATP) to cash later.
The TCA Cycle
The TCA cycle is next. We call it a cycle because it starts at one end and then wraps around, going back to where it started. Like glycolysis, it’s a series of many steps, each requiring an enzyme. I won’t make you memorize it. That would be evil. Right? LOL!!. Here is what you need to get. The cycle produces some more carbon dioxide which we will breathe out through our lungs. Also, and more importantly, it produces 1 GTP (GTP and ATP have the same amount of energy so 1 GTP = 1 ATP), 3 NADH, and 1 molecule of a different “currency” called FADH2 (Flavin Adenine Dinucleotide + 2 Hydrogens). This currency is not as “strong” as NADH. It’s like how the Jamaican dollar is weaker than the US dollar but it still has value. So it’s not like CHI-CHING! but more like…..chi-ching. LOL!. 1 FADH2 values 1.2 ATP.
Electron Transport Chain (ETC)
The final stop in energy production is the electron transport chain (ETC). This is the heart of energy production. This is where BIG, BiG MONEY (energy in the form of ATP) is made guys!!. Remember that this happens in the mitochondria, specifically, in the inner membrane of the mitochondria. The ETC is like a money exchange machine. Some airports are equipped with money exchange kiosks. You put in one currency and it spits out another. This is great when you are doing international travel and need to switch currencies. Let’s say you are returning from a visit to Jamaica where you spent 10 days on a fabulous honeymoon. Back in the US, you will have no use for Jamaican dollars so you need to get it converted. What do you do? You find a kiosk. You slide in your, no longer needed Jamaican dollars, and the machine gives you the equivalent in US dollars. By the way, just a tip, for you. It is better to do your money exchange at a bank. Airport kiosks will give you the worst rates.
How do these kiosks work mechanically? Who cares? You just need to get your money. In this lesson, we don’t really care about how the machine works. Catch me in biochemistry class and we can have fun with that. All we need to know is that we put a currency in the machine (NADH or FADH2) and we get paid ATP. For every glucose molecule, we get 32 ATP molecules. Consider the enormous number of ATP that can be produced from a single grain of rice, given that it consists of thousands to tens of thousands of starch granules, each containing thousands to tens of thousands of glucose molecules. The astronomical amount of ATP that we produce from food tells you the insatiable need that the body has for energy.
We have covered the metabolism of carbohydrates so far, focusing only on glucose. What about the other monosaccharides like fructose and galactose? These monosaccharides and others are also broken down by glycolysis. They are either converted to glucose or channeled into the glycolysis pathway at some point (like joining a highway from a side road).
Proteins can be worked into glycolysis or the TCA cycle too. Proteins are first broken down into amino acids. These amino acids, if not utilized for other important purposes can be deaminated (stripped of their amino group), and their carbon skeleton driven from the “side road”, and directed onto the the glycolysis or TCA “highway” to make energy. The amino group that is stripped off is sent to the liver where it is converted to urea. Urea is then sent to the urine to be peed out.
Fats in the form of triglycerides are lysed in a process called lipolysis (lipo + lysis: the name is not surprising, right?) to make glycerol and fatty acids. Glycerol can be sent to the glycolysis pathway to make pyruvate or can be converted to glucose via gluconeogenesis. The fatty acids get broken down through a process called beta-oxidation which produces acetyl-CoA. We get lots more ATP from beta-oxidation than we do from glucose. The longer the fatty acid, the more ATP you can “earn”. For example, a single palmitate fatty acid of 16 carbons will net about 106 ATP compared to the modest 32 from glucose.
When we are fasting, glucose concentration in the blood is low. This is not good for the brain. It uses 20% of the calories that we eat. It always needs energy and lots of it. Therefore, in cases when we are running low on glucose, acetyl CoA is converted to molecules called ketones. The most important one is beta-hydroxybutyrate which is capable of passing the blood-brain barrier, and hence can go to the brain where it is converted back to acety-CoA. You might ask, why not just send acetyl-CoA directly to the brain? The problem is that acetyl-CoA cannot pass the blood-brain barrier to get there.
Another ketone body is acetone which is not used for energy but is breathed out through the lungs. A chemical-like smell on the breath of someone who is hungry or fasting is probably the smell of acetone.
The breakdown of ethanol produces NADH and acetyl CoA. Acetyl-CoA can then be used to make ATP.
As you might expect, if we consume more food than we can burn, the excess will be stored. Energy can be stored in the form of glycogen which is a short-term storage of energy in the muscle and the liver. In the muscle, glycogen supplies immediate energy to the muscle tissue by converting it to glucose. The glycogen in the liver can be released into the blood to travel to other organs that need it. We have about 12-18 hours of glycogen storage. After that, they are pretty much depleted.
Apart from glycogen, energy can be stored in the form of fat in our adipose (fat) tissues). Fat is produced from acetyl-CoA. If you eat in excess, you will have more than enough acetyl-CoA. The excess will turn into fat.