Week 1 => Intro/Glycolysis/Gluconeogenesis Flashcards
Metabolism
Chemical Processes in a living organisms that are necessary to maintain life
Catabolism
Degradation of cell constituents to release energy and/or to salvage components (Oxidative process overall)
Anabolism transforms _____ into ___
Precursors molecules (aa, sugars, fa, nitrogen bases) to Cellular macromolecules (proteins, carbohydrates, lipids, nucleic acids)
Anabolism
biosynthesis of biomolecules from simpler components (reductive process overall)
Catabolism transforms ___ into ___
Energy-containig nutrients (proteins, carbohydrates, lipids) into Energy-depleted end products (Co2, H2O, NH3)
Energy storage (what?)
Macromolecules as a glycogen (Carbohydrates), triglycerides (fat) and proteins => large energy release
Energy transport (also involved in regulation)
Within the cell of between cells. Mostly monomers such as glucose, fatty acids or amino acids => intermediate energy release
Energy release
Through breakdown of macromolecules = catabolism
Energy storage (how?)
Through synthesis of macromolecules = anabolism
Breakdown couple to ATP synthesis
pyruvate, acetyl-CoA => small energy release
Thermodynamics
Properties of a system, stability of a system in one state vs another
Kinetics
Rate of processes, metabolic flux, enzyme catalysis
Conservation of Energy
Total energy in a closed system is constant. In an open system, the internal energy equal the system energy plus incoming minus outgoing energy.
Entropy (theory)
The overall entropy of the universe cannot decrease. In an open system, entropy cannot decrease without energy expenditure. DISORDER
Metabolically, how would organisms and cells be thermodynamically defined?
An open system
What is the goal an open system?
Maintain homeostasis ( energy level and metabolic composition are kept constant over time)
Autotrophs
self-feeding (synthesize all cell component from simple molecules)
Chemoautotrophs
Derive energy from inorganic oxidation
Photoautrophs
Derive energy from light
Herterotrpohs
feeding on others (need autotrophs for organic molecules)
Enthalpy (energy)(H) favored reaction
reaction of favored if delta H is negative
Entropy (disorder)(S) favored reaction
reaction is favored of of delta S is positive
What causes Gibb’s free energy to lower
- Enthalpy decreases
- Entropy increases (disorder increase)
Negative G
Products more stable than reactants: Favorable reaction
Positive G
Reactants more stable than products: unfavorable reaction
How do catalysts influence G?
They DO NOT influence, only lower activation energy required (increases rate of reaction)
Energy requiring (endergonic)
unfavorable, not spontaneous (G+), increase ATP fuel
Energy releasing (exergonic)
Favorable, thermodynamically spontaneous (G-), energy release used to make ATP
Substrate level phosphorylation
Formation of ATP from ADP and a high-energy phosphorylated intermediate
Catabolism without redox
Fermentation, less ATP
Connect metabolic pathways to ATP production
NAD+/NADH and FAD/FADH2
What determines the amount of energy releases in a catabolic, oxidative pathway?
the oxidative states of substrate and product
Do Fatty acids or carbohydrates catabolism produce more energy?
Catabolism of Fatty acid
Redoxactive cofactors
Pairs of molecules that are interconverted through oxidation/reductions. Always have an oxidized and a reduced form. Connect catabolism, anabolism, and energy
List the four main Redoxactive cofactors
NAD+/NADH, NADP+/NADPH, FAD/FADH2, and ubiquinone
NAD+/NADH
Reduced during glycolysis and other catabolic reactions. Oxidized mostly in electron transport chain
NADP+/NADPH
Oxidized during fatty acid synthesis and other anabolic reactions. Reduced in metabolic reactions
FAD/FADH2
Cofactor that is directly complexed to an enzyme
Ubiquinone (=coenzyme Q)
Accepts two electrons in a stepwise manner to become ubiquinol. Part of the electron transport chain
Metabolic pathways are interconnected in a ___
Dynamic network
How many reactions are required for the conversion of glucose to pyruvate?
10 Reactions
which intermediate can lead to many different pathways?
Glucose-6-phosphate
Committed step
If the first irreversible reaction in a metabolic pathway, whose produce cannot enter other pathways and must complete the remainder of the pathways steps
Glycolysis main reactant and product?
Glucose to 2 pyruvate
Glycolysis ATP yield
2 ATP are invested in the first part of the pathway, 4 ATP are made in the second part of the pathway
What happens to election carriers during glycolysis?
They are reduced
where can glycolysis occur?
Every cell
What source of ATP does not require oxygen and is the only cytosolic source for ATP?
Glycolysis
Glycolysis phase 1
Energy investment phase: phosphrylation of glucose and conversion to 2 molecules of glyceraldehyde-3-phosphate. 2 ATP are used in these reactions
Glycolysis phase 2
ATP production phase: Conversion of glyceraldehyde-3-phosphate to pyruvate and coupled formation of 4 ATP. Reduction of 2 NAD+ to 2 NADH
What must be regenerated, otherwise glycolysis stops?
NAD+
What are the three ways to regenerate NAD+?
1) reduction of pyruvate to lactate (Anerobic)
2) reduction of pyruvate to ethanol (yeast)
3) mitochondrial electron transport chain/oxidative phosphorylation
Why is hemostasis maintained by regulating the flux through the pathways?
*Energy use/production according to needs
*Relatively constant metabolite levels
* Balance supply and demand
Steady state
condition when metabolite levels are constant over time. Thermodynamically determined (energetically lowest state under the conditions). The system strives to return to a steady state
Flux
Overall rate of pathway
Homeostasis
Regulate flux to keep metabolite levels constant
Metabolic pathways must be…
- directional
- never have forward and reverse pathway active at the same time
- be regulated
Substrate/product availability
- changes in substrate or product concentrations
- Affects the flux through reactions close to equilibrium (reversible)
- immediate effects
Regulation of enzyme activity
- Only useful for enzymes catalyzing reactions with a large delta G (irreversible)
- Different mechanisms for enzyme regulation
What allows forward and reverse enzymes to avoid futile cycles?
The enzymes are reciprocally regulated
What type of reaction are the majority of steps in metabolic pathways?
Reversible
Le Chatelier’s principle
When a system at equilibrium is distributed is reacts to minimize the disturbance
What are the 7 reversible steps in Glycolysis?
- phosphoglucose isomerase
- aldolase
- Triose phosphate isomerase
- glyceralhedyde-3-phosphatedehydrogenase
- phosphoglycerate kinase
- phosphoglycerate mutase
- enolase
What are the 3 irreversible steps in glycolysis?
- Hexokinase
- phosphofructokinase
- pyruvate kinase
What are the 3 enzyme activity mechanisms?
a) allosteric control (immediate)
b) covalent modification (minutes)
c) synthesis or deration (hours/days)
Allosteric control types of inhibition
- product inhibition
- feedforward activation
- feedback inhibition
Why are covalent modification often part f the intracellular signaling net work?
It allows the cell to respond to environmental cues
Feedback inhibition
Final products of the entire pathway regulating an irreversible enzyme earlier on in the pathway (typically the committed step)
Aerobic re-oxidation of NAD+?
Oxidative phosphorylation in mitochondria. Mitochondrial conversion of pyruvate to acetyl-CoA and oxidation in TCA cycle
Anaerobic re-oxidation of NAD+?
Cytosolic regeneration of NAD+
What process occurs in the absence of dietary carbohydrates, to produce glucose from non-carbohydrate precursors?
Gluconeogenesis
Where does gluconeogenesis primarily occur?
Liver, some in kidney
Substrates for gluconeogenesis:
pyruvate, lactate, glycerol, most amino acids, all citric acid cycle intermediates. NOT fatty acids!
What is the same between glyconegenesis and glycolysis?
Reversible reactions (near equilibrium)
What glycolytic enzymes are not used for gluconeogenesis?
- Hexokinase
- phosphofructokinase
- pyruvate kinase
Unique gluconeogenesis enzymes
*Glucose phosphatase
* fructobisphosphatase
* phosphoenolpyruvate carboxykinase (PEPCK)
* Pyruvate carboxylase
Pyruvate carboxylase
- Carboxylates pyruvate to oxalacetate
- Requires ATP
- Biotin cofactor (Vitamin B7)
- Mitochondrial enzyme
PEPCK
- Decarboxylates and phosphorylates oxaloacetate to PEP
- Requires GTP
- Cytosolic enzme
Substrates for gluconeogenesis?
Any metabolite that can be converted to pyruvate or oxaloacetate or another glycolytic intermediate (lactate, glucogenic amino acids, glycerol, acetyl-CoA)
GLUT transporter
Facilitated diffusion of glucose (intracellular/extracellular), not glucose-6-phosphate
Hexokinase isoforms accostiated with mitochondira?
I and II
Hexokinase isoforms inhibited by glucose-6-phosphate?
I, II, and III
Hexokinase isoforms not inhibited by glucose-6-phosphate?
IV (glucokinase)
What are glycolysis intermediates used for?
Synthesis of amino acids and lipids
What type of kinetics does PFK-1 show regarding it substrate Fructose-6-phosphate and what does it indicate?
Sigmoidal kinetics and allosteric binding of F-6-P
ATP and glycolysis regulation
Sufficient energy, no need for glycolysis
AMP and glycolysis regulation
Low energy, needs glycolysis. Even little AMP can overcome the inhibition by ATP
What is the most potent activator of phosphofrcutokinase-1
Fructose-2,6-biphosphate (NOT the glycolytic enzyme!!!!)
What prevents glycolysis and gluconeogenesis futile cycle?
Frcutose-2,6-BP
Which enzyme is bifuncional?
Phosphofructokinase 2
What does Frucotse-2,6-biphsophate (F2,6P) activate and inhibit?
Allosteric activation of PFK and allosteric inhibitor of FBPase
