# Metabolism

With Metabolism usually the collection of Metabolites (small molecules) and Metabolite converting enzymes are associated. Sometimes reactions where one or more chemical educt(s) react(s) to form one or more molecule(s) occur(s) spontaneously, but only at very slow rates and many reactions don't occur at all. However, enzymes catalysing these reactions increase the reaction rate significantly. If an enzyme produces a product which is in turn substrate for another enzyme, that a gain produces the substrate for yet another enzyme and so on, the enzymes form a reaction chain that is called a pathway. Sometimes several pathways are highly interconnected and it becomes hard to detect a reaction chain, in this case the term reaction network is more appropriate. Although the structure of metabolism varies among different species, many parts of metabolism are highly conserved and can be found in single celled organisms up to multicellular organisms.

One distinguishes reactions that contribute to the cells energy production by degrading nutrient sources (catabolism) from reactions that construct molecules to produce functional biomass through metabolic reactions (anabolism).

The Central Carbon Metabolism (CCM) contains the essential metabolic reactions an organism needs to produce energy from nutrient sources. It thus contains the so called primary metabolites that are essential the organisms growth and proliferation. Secondary Metabolites on the other hand are employed by organisms to serve a function in a specific ecological niche only.

Central Carbon Metabolism

The CCM is often the starting point for metabolic modelling, as the model can be extended by organism specific reactions. It is therefore worthwhile to elaborate on the function of the CCM and the energy that is produced during the reaction steps.

1. During Upper Glycolysis the six carbon molecule glucose is first phosphorylated and 2 molecules of $ATP$ are invested to then brake the bond and create two three carbon molecules. Each of the three carbon molecules is then degraded to pyruvate in several steps thereby releasing molecules of 2 $ATP$ and 1 molecules of $NADH$. The net energy gain of Glycolysis is therefore 2 $ATP$ molecules and 2 $NADH$ molecules.
2. The product of Glycolysis, pyruvate enters the TCA cycle after decarboxylation to acetyl-coA (two carbons) which give one $NADH$ molecule (2 per glucose) and is converted to citric acid (six carbons). During the further reactions 3 $NADH$, 1 $ATP$ (acctually GTP), 1 $FADH_2$ (times two per glucose molecule) and two carbon molecules in form of $CO_2$ are realised. For one glucose molecule the energy gain is 4 $ATP$ molecules 8 $NADH$ molecules and 2 $FADH_2$ molecule.
3. Cellular Respiration allows to convert $NADH$ and $FADH_2$ into ATP molecules. For each $NADH$ molecule 3 pairs of protons are pumped through the membrane. Each pair produces then one $ATP$ molecule via the ATP Synthase. However, the transport of $NADH$ from Glycolysis into the mitochondria costs one $ATP$. is For each $FADH_2$ molecule 2 pairs of protons are transfered to through the membrane giving 2 $ATP$ molecules per $FADH_2$. Thus the net $ATP$ gain is
• Glycolysis:2 $ATP$ + 2 $NADH$
• TCA cycle:6 $NADH$, 2 $ATP$, 2 $FADH_2$
• Decarboxylation of pyruvate: 2 $NADH$
• Transport from cytosol to mitochondria: 2 $NADH$ -> 2 $ATP$
• Cellular Respiration:10 $NADH$ -> 30 $ATP$ + 2 $FADH_2$ -> 4 $ATP$
• Overall ATP gain per glucose molecule: 2(Glycolysis) + 2(TCA) + 34(Respiration) -2 $ATP$(transport)= 36 $ATP$