Part 2.1 Flashcards
Metabolites are
Central metabolic pathway
products, substrates and intermediates in a metabolic pathway
Krebs cycle
Metabolism is required to do:
1) generate or store energy
2) degrade macromolecular structures
3) Convert carbon forms into precursors for macromolecules
4) polymerize building blocks for macro structures
5) produce and break down specialized messenger molecules
Catabolic pathways
To generate ATP and NADPH
Produce CO2, H2O and NH3
1) glycolysis
2) PPP
3) Krebs
4) Ox phos
5) FA ox
6) Ketone bodies
7) AA degradation
Anabolic pathways
Use metabolites to make cell structures, tissue, health
Use of ATP and NADPH
1) Glycogen biosynthesis
2) Polysaccharide production
3) DNA/RNA
4) Cofactors
5) Lipids
6) Sterols
7) Phospholipids, TG
8) Membranes
9) AA –> Proteins
10) Hormones
How is ATP utilized to create macromolecules?
Energy release due to ATP dephosphorylation used to make carbon bonds between precursor molecules
Electrons move from ATP to C-C bonds
Electron transfer in catabolism
Electron moves from carbon to ATP releasing CO2
Glucose is an electron donor, NAD+/FAD is an electron acceptor
Glucose-6-phosphate as a metabolic intersection
1) glycogen synthesis (regulated) OR glycogenolysis
2) sugar synthesis (reversible, regulated)
3) PPP (irreversible but can loop back to glycolysis)
4) Glycolysis OR gluconeogenesis (regulated, reversible)
Pyruvate as a metabolic intersection
1) glycolysis (product) OR gluconeogenesis (precursor) both regulated and reversible
2) Lactate (reversible)
Acetyl coA as a metabolic intersection
1) Lipogenesis (precursor) OR beta oxidation (product) - regulated, reversible
2) ketone bodies (reversible)
3) Cholesterogenesis (irreversible, regulated)
4) Krebs –> AA (reversible) –> acetyl coA (one way)
In intersections of glucose metabolism which pathways only go 1 direction?
Pyruvate –> Acetyl coA
Acetyl coA –> Krebs
Acetyl coA –> cholesterol
Amino acids –> acetyl coA
G6P –> PPP (regen G6P in non-ox phase) –> glycolysis
which pathways are regulated in glucose metabolism?
1) sugar –> G6P (rev), hexokinase/glucokinase
2) Glycogen –> G6P (rev), glycogen phosphorylase
3) G6P –> pyruvate (rev), PFK-1, pyruvate kinase
4) Acetyl coA –> FA (rev), FA synthase
5) Acetyl coA –> cholesterol (one way), HMG-coA reductase
6) Krebs cycle and electron transport chain, citrate synthase, isocitrate dehydrogenase and a-ketoglutarate dehydrogenase
Pathways connected to metabolic intersections cannot happen simultaneously and thus must be regulated heavily (based on demands)
Permeability of the mitochondrial inner membrane
selectively permeable - determined by transporters (large proteome)
- Any protein spanning membrane must be translocating something (True for ETC proteins )
Outer membrane is freely permeable to ions, pyruvate, etc
What signals insulin release from beta cells?
ATP production
Glucose yields how many kJ of energy?
Complete oxidation to CO2 and H2O yields -2840 kJ/mol of energy
4 main fates of glucose?
1) glycogen storage (energy storage)
2) production of polysaccharides for glycoproteins
3) PPP to produce ribose
4) energy production - pyruvate, krebs cycle, oxidative phosphorylation
Why is ATP a poor allosteric regulator?
And AMP?
ATP levels do not vary much in mammalian cells
AMP is the cell’s fuel gauge
- if [AMP] is high, energy demand is high and ATP production increases
- if [AMP] is low, low energy demand and ATP production is inhibited
AMPK activity heavily influences metabolism
Anaerobic glycolysis
Ex. RBC
Glucose —> Pyruvate via glycolysis produces 2 net ATP and 2 pyruvate
2 pyruvate —> 2 lactate and 2 NAD+ fueled by 2 NADH from glycolysis
Allosteric regulators of hexokinase vs glucokinase
Tissues where found
HK Activator: Pi (inorganic phosphate)
HK Inhibitor: G6P
All tissues
GK Activators: Glucose and insulin
GK Inhibitors: Glucagon and Fructose-6-Phosphate
liver, enterocytes of SI, and pancreatic B cells
ChREBP function and ChoRE function
ChREBP allosteric and non allosteric activators
ChREBP - carbohydrate response element binding protein positively activates glycolysis and genes for lipogenesis by binding ChoRE with co-activators derived from glycolysis metabolites
ChoRE can be found in promoter of genes related to: glycolysis, gluconeogenesis, lipogenesis, hormone receptors, etc
G6P is an allosteric activator of ChREBP
F-2,6-BP and X5P activate ChREBP
*X5P by dephosphorylation from PP2A (protein phosphatase 2A)
BOTH G6P + X5P are required for ChREBP nuclear localization
Signalling activator: F2,6BP
1) directly activates ChREBP which induces lipogenesis genes
2) activates PFK-1 to increase glycolysis
3) increased glycolysis leads to increased Krebs citrate production which also stimulates lipogenesis
*linking glycolysis and lipogenesis
Hypoxia Inducible Factor-1 (HIF-1) function in normative and hypoxic conditions
HIF-1 gene
HIF-1 is constitutively expressed (always expressed)
Normoxia: HIF-1a is degraded by PHD (prolyl hydroxylase marks it for degradation)
Hypoxia: PHD can’t do its job so HIF-1a + HIF-1b interacts with p300 and acts as TF to HIF-1 gene
HIF-1 gene: increases anaerobic glycolysis, vascularization, Fe uptake, and erythropoiesis
*such as in solid tumor cancer cells which tend to be hypoxic
Broad categories of HIF-1 oncogenic activity
Increased: survival, metastasis, angiogenesis, chemoresistance, metabolism, invasion and proliferation
AMP is an allosteric regulator for which glycolytic enzyme?
ADP?
ATP?
AMP activates PFK-1
ADP activates PFK-1
ATP inhibits PFK-1 and pyruvate kinase
Citrate is an allosteric regulator for which glycolytic enzyme?
Citrate inhibits PFK-1
F-1,6-BP is an allosteric regulator for which glycolytic enzyme?
F-2,6-BP is an allosteric regulator for which glycolytic enzyme?
F-1,6-BP inhibits pyruvate kinase
F-2,6-BP activates PFK-1
Insulin and glucagon are allosteric regulators for which glycolytic enzymes?
Insulin activates glucokinase and pyruvate kinase
Glucagon inhibits glucokinase and pyruvate kinase
Alanine is an allosteric regulator for which glycolytic enzyme?
Alanine inhibits pyruvate kinase
