Energy Supply: How Your Muscles Produce ATP
1. Introduction
Whether it's nerve cells transmitting electrical impulses or muscle cells performing mechanical work, every cell in the human body needs energy. This energy is stored inside the cells in the form of adenosine triphosphate (ATP) and is released when ATP splits into adenosine diphosphate (ADP) and free phosphate (Pi). Since only a very limited supply of ATP is stored in the muscles, it must constantly be replenished by converting ADP and Pi back into ATP. This regeneration takes place via 3 different systems, whose expression is matched to the properties of the muscle fibres (essentially the MyHC isoform, "in other words, the muscle fibre type"). The systems are
- the phosphagen system (highest metabolic power but lowest capacity
- the glycolytic system (lower metabolic power but higher capacity than the phosphagen system)
- mitochondrial respiration (lowest metabolic power, but by far the greatest capacity)
2. The phosphagen system
ATP resynthesis via the phosphagen system takes place in the cell plasma and comprises two chemical reactions through which the muscle fibre can recover ATP relatively quickly (the creatine kinase and adenylate kinase reactions). 85% of the system's already modest capacity is limited by the size of the intracellular phosphocreatine stores (PCr), while the remaining 15% comes from energy production via the adenylate kinase reaction.
- Creatine kinase (an enzyme) catalyses the reaction of ADP and PCr to ATP and creatine (the creatine kinase-PCr system)
- Adenylate kinase (an enzyme) converts 2 parts ADP into 1 part ATP and 1 part AMP (adenosine monophosphate)
AMP and its breakdown products play a central role as intracellular signalling molecules. For example, AMP indirectly stimulates the transport of glucose and fatty acids into the muscle cells as well as the metabolism of these energy substrates in the mitochondria. It also indirectly stimulates the breakdown of glycogen. Finally, it's linked to mitochondrial biogenesis, and the intracellular concentrations of ADP and creatine stimulate mitochondrial respiration. The breakdown products of ATP splitting and the components of the phosphagen system therefore directly influence the other two energy supply systems. Because the phosphagen system is supported by the other two systems right from the start, it can contribute significantly to energy supply for more than 20 s. If it were left on its own, the PCr stores would already be exhausted after 10 s. The phosphagen system is what lets us buffer fast, short-term changes in ATP demand in everyday life (e.g. getting up from a chair, going from walking to sprinting, etc.). The phosphagen system is particularly well developed in type II muscle fibres compared with type I muscle fibres.
3 The glycolytic system
The glycolytic system comprises the biochemical process of glycolysis. Like the processes of the phosphagen system, this takes place in the cell plasma. The starting point of glycolysis is
glucose-6-phosphate, which can come either from free glucose (blood sugar from food intake, broken-down liver glycogen, or gluconeogenesis from amino acids in the liver) or from the direct breakdown product of muscle glycogen. Like the phosphagen system, the glycolytic system is better developed in type II muscle fibres than in type I muscle fibres, with type II muscle fibres also having larger glycogen stores than type I muscle fibres and being better able to break down glycogen. Type II muscle fibres are therefore geared towards "processing" ATP via the glycolytic system. Intensive muscular strain such as muscle training therefore means that, because the large motor units are recruited, it's primarily the glycogen stores of the type II muscle fibres that are depleted, whereas endurance training mainly depletes the glycogen stores of the type I fibres.
At the end of the 10 steps of glycolysis stands the molecule pyruvate. This can now either be converted into lactate in the cell plasma or channelled into the citrate cycle in the mitochondria.
If the pyruvate from glycolysis is converted into lactate, this is called anaerobic glycolysis. This isn't because no oxygen is present, but simply because these reactions don't require any oxygen at all. The conversion of a) pyruvate to lactate and b) the reverse is catalysed by different forms of the enzyme lactate dehydrogenase, with, for example, a) predominating in type II muscle fibres and b) in type I muscle fibres. Put simply, the glycolytic muscle fibres produce lactate and release it into the blood. The oxidative muscle fibres then take up the lactate, convert it back into pyruvate and oxidise it. Other organs also take up lactate from the blood and use this energy-rich molecule as a starting substance for metabolic processes (liver: gluconeogenesis and energy production; heart, brain, kidneys: energy production). Contrary to popular belief, lactate is therefore not a waste product of anaerobic metabolism. It always leaves the glycolytic muscle cell and enters the blood in combination with a proton, via specific transporters (uptake into the oxidative muscle fibres also happens via transporters).
If the pyruvate isn't converted into lactate, it enters the mitochondrion and is converted via pyruvate dehydrogenase into acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is the starting substance for aerobic energy supply in the mitochondrion. This is why, in this case, we speak of aerobic glycolysis ("using oxygen", not "in the presence of oxygen"). In addition to being produced from pyruvate, acetyl-CoA can also be produced in the mitochondria from fatty acids via the process of β-oxidation. The fatty acids reach the muscle fibres from the blood via fatty acid transporters, with type I muscle fibres better equipped with these transporters than type II muscle fibres. In the cell plasma of the muscle fibres, the fatty acids are activated and then transported into the mitochondria. For this purpose, they're briefly bound to carnitine. Carnitine therefore acts as a shuttle in fat metabolism. Without carnitine, no fat could be metabolised. Carnitine also buffers acetyl-CoA whenever high muscular strain produces more acetyl-CoA than can be fed into the citrate cycle in the short term. A backlog of acetyl-CoA inhibits the oxidation of fatty acids and increases the production of lactate.
4 Mitochondrial respiration
Inside the mitochondria, acetyl-CoA is now produced from the activated fatty acids via β-oxidation. It's then metabolised further in the citrate cycle, just like the acetyl-CoA from pyruvate, ultimately using ADP and Pi to regenerate ATP. In the citrate cycle, acetyl-CoA gives rise to carbon dioxide (CO2; diffuses into the blood and is exhaled via the lungs) and reducing equivalents
(molecules that transfer hydrogen and/or electrons). The reducing equivalents then travel along the inner mitochondrial membrane from protein complex to protein complex and are ultimately transferred to oxygen, releasing water and heat in the process. This complex process creates an electrochemical potential, the energy of which is used for ATP resynthesis. Mitochondrial oxygen consumption therefore determines the body's oxygen requirement.
