Principles of Metabolic Pathway Regulation

Question 1

fate of glucose-6-phosphate in hepatocytes

Answer 1

glycolysis, pentose-phosphate pathway, polysaccharide synthesis, glucose, other sugar synthesis, FA or sterol synthesis

Question 2

allocation of metabolites to

Answer 2

maintain homeostasis (requires energy)
manage precursor supplies
changing energy demands
dynamic steady state maintenance (intermediates are formed and consumed at equal rates)
ex. nutrients –> blood glucose –> glucose utilization
different cells have different metabolic needs

Question 3

cells can have transient needs or permanent ones like:

Answer 3

Maintenance of homeostasis due to transient input

If not transient, requires production of components, permanent change of components

Cells require different metabolic pathways
RBC example of non-transient perturbation (nucleus removal)

Question 4

10 principles of enzyme regulation

Answer 4

1-6 related to enzymes can be measured in enzymatic levels (Western blot)
1. extracellular signal
2. transcriptional regulation (TF phosphorylation/dephosphorylation and interactions)
3. mRNA stability
4. mRNA translation
5. protein stability/half-life
6. enzyme localization

7-10 cannot be measured
7. changes of levels of substrate
8. allosteric effectors (enzyme binding)
9. covalent modifications leading to conformational change (phosphorylation for example)
10. interactions with regulatory proteins

Question 5

Extracellular signal regulation

Answer 5

enzyme quantity, regulation of activity of an existing molecule

Question 6

transcription factor regulation

Answer 6

phosphorylation/dephosphorylation
TF can change number of enzymes in a pathway
can bind directly to DNA or alter a ligand
TF interactions

Question 7

Protein stability regulation

Answer 7

Protein half lives varying significantly depending on tissue location

Ex. Cyclin ubiquitin covalently attached so the protein is degraded very quickly
Rate of protein degradation is stable

Question 8

enzyme localization regulation

Answer 8

Sequestration of enzyme inside an organelle restricts activity of that enzyme
ex. mitochondrial enzymes

Question 9

Common regulatory mechanisms at the organism level

Answer 9

• Opposite pathways are not favored simultaneously (1 path will dominate)
• maximization of product utilization (glycolysis and gluconeogenesis)
• partitioning of metabolites into different pathways
• draw on fuel best suited to need
• negative feedback of synthesis when products build up

Question 10

cells regulate their metabolism by

Answer 10

either changing activity of existing enzymes or changing number of specific enzymes

Question 11

changes in transcriptome (full range of molecules expressed by a cell) lead to

Answer 11

changes in proteome (complete set of proteins made by a cell) and metabolome (totality of metabolism) of cell

Question 12

dynamic steady state maintenance

Answer 12

intermediates are formed and consumed at equal rates