Carbohydrates in the form of glucose is the main source of energy for the body. Energy is needed for two types of metabolic processes; anabolism and catabolism. Anabolism is the process of making larger molecules using smaller molecules e.g. using fatty acids to make fats, or amino acids to make protein. Catabolism accomplishes the opposite i.e. break down of larger molecules to smaller ones e.g. breakdown of fats to fatty acid and glycerol, or breakdown of proteins to amino acids. Energy in the body is stored in the form of Adenosine Triphosphate (ATP) this is a high-energy molecule that releases energy when it is broken down. ATP production occurs either in the cytosol of the cell or mitochondria. Before we jump into how energy is produced, it is important to known some basic processes that typically occurs during metabolic reactions. These include condensation, hydrolysis, phosphorylation and oxidation-reduction (Redox) reactions.
- Condensation (or dehydration reaction): Reaction resulting in loss of water
- Hydrolysis: Compound-splitting reactions using water
- Phosphorylation: Reaction involving exchange of phosphate group
- Oxidation-Reduction (Redox): Reaction involving simultaneous loss of electron or hydrogen (oxidation) and gain of electron or hydrogen (reduction)
Metabolic reactions occur with the help of many enzymes. Enzymes are proteins that catalyze chemical reactions without being changed themselves. Many enzymes cannot work without the help of cofactors (non-organic substances such as minerals) and coenzymes (organic substances such as vitamins).
Energy Production (Aerobic Respiration)
Following absorption of glucose in the small intestine, glucose has several fates. It may either be:
- Stored as glycogen
- Metabolized in the liver for energy
- Metabolized in the liver to make other compounds
- Released for circulation into the blood
- Stored in fat (adipose) cells
The other monosaccharides (galactose and fructose) are either converted to glucose or channeled into the glycolysis pathway; the process that I will talk about next. Energy production is completed via three steps. These are glycolysis, the tricarboxylic acid (TCA) cycle, (also called the citric acid or Kreb cycle), and the electron transport chain.
Glycolysis is a series of 10 enzyme-dependent steps occurring in the cytosol of the cell. The process is responsible for converting glucose to pyruvate, the raw material for the TCA Cycle. The first and third steps require inputs of energy in the form of ATP. Later on, four ATP molecules are made (steps 7 and 10) resulting in a net production of 2 ATPs. In addition, glycolysis makes 2 molecules of nicotinamide adenine dinucleotide (NADH) which will be used in ATP production later on.
Pyruvate from glycolysis may be converted back to glucose through an oxygen-depended process called gluconeogenesis if energy is not needed right away. Otherwise, it proceeds to the TCA cycle. Unlike glycolysis which can occur without oxygen, the TCA cycle needs oxygen. If there is none, pyruvate is converted to lactate in the muscles. This happens when your muscles are fatigue from exercise. This can be very painful as you know. Lactate is used to create a small amount of energy to keep you going by regenerating NADH which is needed for glycolysis. Since glycolysis produces only 2 ATPs, the process is not very efficient. So before long you will have to strop stressing your muscles and take a rest. The process of making energy from lactate in the absence of oxygen is called anaerobic fermentation. During rest and recovery, lactate is converted back to glucose in the liver. This cycle is known as the Cori Cycle.
The TCA Cycle
At the end of glycolysis, pyruvate moves out of the cytosol and into the matrix (inner part) of mitochondria where it is oxidized resulting in the production of acetyl coenzyme A (CoA) and NADH as a byproduct. Acetyl CoA then combines with oxaloacetate to form citrate. This is the reason the cycle is also called the citric acid cycle. Oxaloacetate by the way is only produced from carbohydrate food sources. Hence a low-carb diet can leave you feeling tired and lethargic. As the cycle progresses, 1 ATP, 3 NADH and 1 flavin adenine dinucleotide (FADH2) are produced along with 2 CO2 which we breath out. Since two pyruvate molecules are made in glycolysis, the TCA cycle will produce twice this yield. NADH and FADH2 are important molecules used in the next step (electron transport chain) to make ATP. NADH is derived from the B vitamin niacin (B3), while FADH2 is derived from the B vitamin riboflavin (B2).
So far we have covered digestion, glycolysis and the TCA cycle. The whole point of these processes is really to make ATP. Yes, that’s the fireworks, the grand finale! However we have seen that there is not a lot of ATP produced up to this point, but we have made a fair amount of NADH and couple of FADH2. These compounds will be used as ingredients to make ATP. So here is what we have so far.
|Respiration Step||Net ATP||Net NADH||Net FADH2|
|Oxidation of Pyruvate||0||2||0|
The next step of energy production, is called oxidative phosphorylation which occurs in the membrane of the mitochondria (recall that the TCA cycle occurs in the matrix (inside) of the mitochondria and not in the membrane. Oxidative phosphorylation is a process whereby ATP, a phosphate-containing energy molecule, is made. It is also referred to as the electron transfer chain (ETC) since it resembles a chain reaction involving the transfer of electrons from one step of the chain to the next.
The diagram below illustrates how the ETC works, following the chemiosmosis or chemiosmotic model. Chemiosmosis is the movement of ions across a semi-permeable membrane which is what occurs in the ETC. I’ll explain. The model includes the following components:
- NADH dehydrogenase (Complex I)
- Succinate dehydrogenase (Complex II)
- Cytochrome oxidoreductase (Complex III)
- Cytochrome oxidase (Complex IV)
- ATP synthase (Complex V)
- Coenzyme Q (CoQ) or Ubiquinone
- Cytochrome c
NADH from the TCA cycle interacts with Complex I and gives up two electrons to form NAD+. These electrons are snatched up by the CoQ electron carrier and carried over to Complex III. Another carrier, Cyt c snatches the two electrons and carries them across to Complex IV. The electrons then travels down Complex IV and delivers the electrons to oxygen. At the same time, oxygen reacts with hydrogen protons to form water. We give off some of this water when we perspire.
Electron transfer result in protons (hydrogen) being pumped from the matrix into the intermembrane space (space between inner and outer membrane) of mitochondria, creating a chemiosmotic gradient. Specifically, for every two electrons transferred to the chain, there are 4, 4 and 2 protons pumped out of the membrane by Complex I, III and IV respectively. To create balance, protons are pumped back into the matrix via the complex IV (ATP Synthases). For every 4 protons that ATP synthase accepts, 1 ADP is converted to ATP. Oh by the way, I have not mentioned Complex II in this whole transaction. Well, Complex II is very much involved. Remember that FADH2 is also produced in the TCA cycle. FADH2 hand over two electrons to Complex II in the ETC to form FAD. These two electrons are also snatched up by CoQ and then shuttled off along the chain to also contribute to ATP production in just about the same way as NADH2. However the only difference is that FADH2 contributes to 1.5 ATPs for every two electrons compared to NADH which contributes to 2.5 ATPs for every two electrons it transfers. That is,
NADH produces 10 protons for ATP to pump back in: 10/4 = 2.5 ATPs,
FADH2 produce 6 protons for ATP to pump back in: 6/4 = 1.5 ATPs
Therefore what’s the total number of ATPs produced by aerobic cellular respiration? Here it is:
|Respiration Step||Calculated ATPs|
|Glycolysis||2 ATP = 2 ATP, 2 NADH x 2.5 = 5 ATP|
|Oxidation of Pyruvate||2 NADH x 2.5 = 5 ATP|
|TCA Cycle||2 ATP = 2 ATP, 6 NADH x 2.5 = 15 ATP, 2 FADH2 x 1.5 = 3 ATP|
Reference: Thompson,& J., Manore, M., Vaughan, L. (2020). The science of nutrition (5th ed.). New York. Pearson