329

https://link.springer.com/chapter/10.1007%2Fb137745 or even more recently). Typically,

such enzymes are located at the beginning or end of a metabolic pathway. Equally impor­

tant is the exactness of the coding (see above, e.g. Task 7.1.). If the enzymes involved have

a broader specificity or the enzyme is poorly positioned (for example, at a metabolic

branch), several pathways are thus altered at once, but this is sometimes biologically

intended.

Question 7.12

Several enzymes are radically switched (“moonlighting”). As long as there is sufficient

substrate, they function as metabolic enzymes. If there is too little substrate, however,

these enzymes become regulatory active. A nice example is aconitase, which normally

produces isocitrate from citrate as the first step in the citric acid cycle. In the case of iron

deficiency, the iron-sulfur cluster in the active site is missing, and the enzyme then func­

tions instead as iron-responsive element-binding protein 1 and binds to RNA, namely iron-­

responsive elements.

A good link to this are moonlighting databases, for example: https://www.moonlight­

ingproteins.org (even the cover image fits there ☺). Also nice is: https://www.uniprot.org/

database/DB-0189.

Question 7.13

(a) On the one hand, this can be used for energy production, for example glycolysis

and gluconeogenesis occur simultaneously (“futile cycles”). Happens in the brown

fat of newborns (and other young mammals). This leads to a much more sensitive

response to metabolic changes when both pathways run simultaneously (again, like

the initial example of glycolysis and gluconeogenesis). Therefore, it is even pos­

sible to determine the futile cycles with the help of software such as Metatool or

YANA (see Chap. 4), and the enzymes involved there are then quite often the

enzymes that play a special role in regulation.

(b) For example, flow 100 in BOTH directions. Net result is then zero, nothing is

moved. But if I now have 10% enzyme change, without the futile cycle I would

only have 10% change in one direction. So now that I have sacrificed some meta­

bolic energy through the futile cycle, I get a much higher sensitivity: execution

changes from 100 to 110%. But the reverse direction changes from 100 to 90%. So

now the net difference is twice as much, 20% regulation. Of course, this also goes

further “down” for each real situation, so e.g. glycolysis is just at 110% and gluco­

neogenesis at 90%, the net result for glycolysis is then 20%. If I now have another

10% change in regulation, glycolysis changes to 120% and gluconeogenesis only

has 80%, but with that even a total of 40% difference and increase to glycolysis.

20.7  How to Better Understand Signal Cascades and Measure the Encoded Information