Glucose metabolism + its regulation

Question 1

Define metabolism

What are metabolites?

What is cellular metabolism required for?

Answer 1

Metabolism: Sum of all highly coordinated chemical transformations taking place within a cell or organism, which ivolves multiple eznyme-catalyzed reactions that are part of metabolic pathways.

Metabolites: products, substrates and intermediates of metabolic pathways that are generated by the metabolism of different nutrients.

Required for:
-generation or storage of energy
-degradation of macromolecular structures
-conversion of disparate forms of carbon into precursors required to generate macromolecules (building blocks)
-polymerization of builsing blocks to generate macromolecular strcutures
-prodcution and break down of specialized molecules used as intracellular messengers.

Question 2

Describe ATP, how its generally made, its use and how it links catabolism and anabolism.

Answer 2

ATP: adenosine triphosphate. Made of adenosine (purine nitrogeneous base), a ribose and 3 phosphate groups.

Generated in mitochondria through oxidative phosphorylation.

Transported in the cell to perform useful work (locomoton, neural activity, heart beat)

Catabolism extracts electrons from carbon to fuel ATP production by phosphorylating ADP.
Anabolism dephosphorylates ATP into ADP to make new carbon bonds between precursor molecules, making macromolecules

Key message: ATP produced by catabolic reactions support and fuel anabolic reactions (cell building rx).

Question 2

What is catabolism and anabolism? Name examples

Answer 2

Catabolism: degradation/break down of metabolites, notably carbon of sugars, fats and AA.
-breaks bonds to release energy trapped within them to generate electron carriers and ATP.
-Ex: AA degradation, ketone bodies, FA oxidation, CAC, oxidative phosphorylation, PPP, glycolysis.

Anabolism: production/biosynthesis of metabolites (simple precursors -> complex molecules)
-forms bonds to make proteins (cell and physiological fct), fats (energy storage, hormones, lipid membrane) and genetic material (DNA, RNA)
-precursors include: AA, acetyl-CoA, sugars
-Ex: glycogenesis, gluconeogenesis, cholesterogenesis, nucleotide production, protein biosynthesis, lipidogenesis, etc..

Question 2

What are redox reactions? What is the link between redox reactions and energy metabolism (with example)?

Answer 2

Redox reactions: successful transfer of electrons between donor and acceptor molecules. Oxidizing a substrate to reduce a product (Ex: glucose oxidization to reduce electron carriers).
-prepare molecules for further anabolism/catabolism

Energy metabolism depends on redox reactions (core of cellular metabolism).
Ex: catabolic production of ATP by aerobic respiration and oxidative phosphorylation requires removal of electrons from fuels (glucose, electron donors) and their passage to electron carriers (electron carriers such as NAD+ and FAD).

NAD+/FAD + e- => reduced to NADH/FADH2

Question 3

Describe the CAC’s central anabolic nature (What anabolic reactions are fueled by CAC?)

Answer 3

AcetylCoA -> Lipogenesis, cholesterogenesis -> TG, lipoproteins, membranes

Nucleotides -> DNA/RNA

Heme, Fe-S clusters, Urea cycle, hormones

AA -> Protein biosynthesis

Oxaloacetate -> PEP -> gluconeogenesis -> glucose -> glycogenesis

Question 4

What are metabolic intersections?

What are 3 key metabolites that serve as metabolic intersections in glucose metabolism? For what metabolic pathways?

Answer 4

Metabolic intersections: points in metabolic pathways where different biochemical processes converge or share substrates, enzymes, or products. Connected pathways cannot operate simutaneously and are thus subjected to heavy regulation.

Glucose-6-phosphate: reversible step towards glucose or pyruvate
-involved in glycogen synthesis and glycogenolysis.
-involved in glycolysis and gluconeogenesis
-involved the pentose phosphate pathway.

Pyruvate: reversible step towards G6P and irreversible step towards acetyl-CoA
-involved in lactate production/lactate degradation

Acetyl-CoA: irreversible step from pyruvate, reversible step towards the CAC
-involved in cholesterogenesis and degradation of ketone bodies
-involved in beta-oxidation and lipogenesis.
-can be obtained from AA degradation.

Question 5

Describe cellular respiration.

Answer 5

1. Glycolysis: in the cytosol
   -substrate level phosphorylation produces ATP
   -production of NADH
   -glucose -> pyruvate
   -pyruvate goes through mitochondrial intermembrane space to enter mitochondrial matrix (pumped through, required energy).
2. Decarboxylation of pyruvate: in mitochondrial matrix
   -yields NADH
   -pyruvate -> acetylCoA
   -AcetylCoA enters CAC
3. TCA cycle: in mitochondrial matrix
   -yields CO2, GTP, FADH2, NADH
4. Oxidative phosphorylation: inner mitochondrial membrane
   -C1, C3 and C4 pump protons in intermembrane space to establish proton gradient (becomes acidic/postive).
   -matrix becomes negative/basic.
   -pmf drives ATP synthesis

Question 6

What are metabolic intersections key for? What metabolic intersetions serve as a key site for regulation?

What is a general rule for identifying an irreversible reaction?

Where can AA be supplied from in metabolism?

Answer 6

Metabolic intersections are key for metabolic regulation by hormones (ex: insulin and glucagon).
Enzymes that catalyze irreversible metabolic reactions are key sites for regulation.

General rule: if its making or consuming ATP, it’s generally an irreversible reaction.

**AA can be supplied from the CAC (through proteolysis, etc..)

*can it be supplied from elsewhere, ex: msc?