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What would the head group of a Glycerophospholipid be?
The PHOSPHATE containing group because it’s POLAR.
What are the 2 atoms that came from SERINE in a SPHINGOLIPID?
NH, H (serine gives the amine group)
What lipid is more likely to be found on the OUTER leaflet of a neuron?
Sphingolipid is often found on the outside
Why is CHOLESTEROL so important? (2 reasons)
1) Regulates membrane fluidity
2) Broadens the melting temperature to prevent abrupt phase changes
What are the 3 types of MOVEMENT a LIPID can undergo within a membrane?
1) LATERAL diffusion : side to side
2) ROTATIONAL diffusion: spinning in place
3) FLIP-FLOP/TRANSVERSE diffusion : moving to the other leaflet
Why can CHOLESTEROL rapidly flip from one leaf to another but NOT CEREBROSIDES?
Cholesterol → mostly hydrophobic (nonpolar) so it can easily flip across
Cerebrosides → has big, charged (polar) head group so it can’t flip easily across the membrane
Transport - If glucose concentration in the blood is very high and is transported INTO red blood cells?
Glucose = polar = facilitated
→ protein is needed
→ no ATP needed
Transport - if glucose concentration very high INSIDE cells that line small intestine, after meal glucose in lumen (inside) is transported INTO cells. (Low→high)
Low in lumen, high inside so against gradient
→ ACTIVE transport
→ glucose = polar = PROTEIN NEEDED
→ Yes, ATP needed (active)
Transport - cells in culture incubated with 5% oxygen, which is transported INTO cells
Oxygen is small and non polar, can pass easily in and out = SIMPLE diffusion
→ simple means no proteins needed
→ no ATP needed
Passive vs Faciliated
Facilitated = membrane protein required
Passive= no proteins needed
2 Structural Classes of TRANSMEMBRANE PROTEINS
1) Alpha-helical transmembrane protein
-H bonds within the helix
2) Beta-Barrel transmembrane protein
-H bonds between beta strands inside the closed barrel
Why are proteins involved in transport (transmembrane) either alpha-helical or beta-barrel?
Helices and Barrels HIDE EXPOSED POLAR GROUPS via INTERNAL H BONDING in the hydrophobic membrane interior.
GLUCOSE-6-PHOSPHATE - why is it regulated but NOT a COMMITTED step?
G6P is a BRANCH POINT for other metabolic pathways
→ it can go into glycolysis, glycogen synthesis, PPP
→ it doesn’t HAVE to go into glycolysis, therefore its not committed
ENZYME for glycolysis v gluconeogenesis
A= Glucose
B= Glucose-6-Phosphate (G6P)
Glycolysis (A→B) = Hexokinase
Gluconeogenesis (B→A) = Glucose-6-Phosphatase
ENZYME for glycolysis v gluconeogenesis
A= Fructose-6-Phosphate
B= Fructose-1,6-Bisphosphate
Glycolysis (A→B) = PFK
Gluconeogenesis (B→A) = Fructose-1,6-Bisphosphatase
ENZYME for glycolysis v gluconeogenesis
A= Phosphoenolpyruvate
B= Pyruvate
Glycolysis (A→B) = Pyruvate Kinase
Gluconeogenesis (B→A) = 2 FOR THIS = PEPCK, Pyruvate Carboxylase
Last 7 Steps of Glycolysis are REVERSIBLE
-What does this say about DELTA G of each reaction?
-How does METABOLITE CONCENTRATION help in deterring which pathway is activated?
1) Reactions both have a net Delta G near 0 (reversible)
2) The metabolite concentrations determines the DIRECTION via Le Chatlier’s principle
Why is STEP 6 (addition of phosphate group via oxidation) HIGHLY UNFAVORABLE, how does this manage to happen?
Step 6 is COUPLED to a FAVORABLE, SUBSTRATE-LEVEL PHOSPHORYLATION of Step 7, where ATP is formed!
Why do cancer cells prefer glycolysis, it only produces a small amount of ATP?
Because it is ANAEROBIC (doesn’t require oxygen) and produces ATP more quickly.
What COFACTOR is needed for GLYCOLYSIS?
NAD+
How does cancer cells ensure there is enough NAD+ for glycolysis?
They REGENERATE NAD+ by converting PYRUVATE into LACTATE, which then oxidizes NADH back into NAD+.
*Pyruvate to Lactate gives NAD+ back
What does the muscle convert in the CORI CYCLE?
Glucose → Lactate
Via Glycolysis
CATABOLIC, breaks down glucose to do so
What does the liver break do in the CORI CYCLE?
Lactate → Glucose
Via Gluconeogenesis (generating new glucose )
Anabolic, bc its building new glucose molecules
Glycogen Metabolism - what activates SYNTHESIS?
Synthesis → store glucose ( anything that means high glucose, high energy, fed state)
Degradation → break down glycogen ( anything that means low glucose, stress, emergency)
Glucose-6-Phosphate → activate synthesis or degradation?
Synthesis
G6P means that there is already plenty of glucose in the cell.
There is already plenty of fuel → store some of it as glycogen
ATP → activate synthesis or degradation?
Synthesis
ATP means cell has lots of energy (energy abundant)→ high energy= does not need to break down
→ stores glucose for later
Fructose-2,6-bisphosphate → activate synthesis or degradation?
Synthesis
Goes along with conditions where glucose is available, so body is more likely to store
Think of it as a “fed” state
Insulin → activate synthesis or degradation?
Synthesis
Insulin = blood glucose is high = take in glucose and store it as glycogen
Glucagon → activate synthesis or degradation?
DEGRADATION
(Glucagon sounds like glucose gone)
Released when blood sugar is LOW, tells liver to break down glycogen so glucose can be made available
Epinephrine→ activate synthesis or degradation?
DEGRADATION
(Emergency, break down fast)
Fight or flight state/emergency = wants quick fuel now = break down glycogen fast
Degradation of glycogen - requires phosphorylation of glucose from the NON REDUCING END via the use of a PHOSPHORYLASE than a KINASE
→ why is this BENEFICIAL?
Phosphorylases - use an INORGANIC PHOSPHATE (without needing to spend ATP), while kinases use ATP.
Using ATP to break down glycogen would reduce the NET energy yield (wastes ATP).
PPP primary product = NADPH
Why is NADPH used for in RBCs and why is it IMPORTANT?
Used to maintain the REDUCED form of GLUTATHIONE, which protects against damage from oxidation.
2 Uses of the Pentose Phosphate Pathway (PPP)
1) Makes Ribose-5-Phosphate
2) Converts Pentoses → Hexoses & Trioses
Compare and contrast - THIOESTERS vs ATP
BOTH = release the SAME amount of energy (~30kJ/mol)
THIOESTERS = NOT resonance stabilized, therefore more REACTIVE
ATP = resonance stabilized, not stored in the cell, bond cleavage is entropically favorable
Pyruvate Dehydrogenase Complex - Converts Pyruvate → Acetyl-CoA
What cofactors are ASSOCIATED permanently? (3)
TPP, FAD, Lipoic Acid
(Built in)
Pyruvate Dehydrogenase Complex - Converts Pyruvate → Acetyl-CoA
What cofactors DISSOCIATE? (2)
CoA, NADH
(Travellers)
Pyruvate Transportation from Cytoplasm to Mitochondria to be made into Acetyl-coA
Describe how it crosses the outer and inner mitochondria membrane:
Diffuses across the outer membrane (permeable)
Transported with a protein into the inner membrane (facilitated)
What does a high concentration in the liver of Fructose-2,6-Bisphosphate mean?
It will ACTIVATE PFK-1 → major regulatory enzyme of glycolysis
(Phosphofructokinase 1)
Which of the following can move 2 different molecules in the SAME direction at the same time?
Symporter
Under ANAEROBIC conditions, the NAD+ required to continue w/ glycolysis is generated by what enzyme?
LACTATE DEHYDROGENASE
→ pyruvate → lactate
Converts NADH back to NAD+
G6PD (glucose-6-phosphate dehydrogenase) → mutations occur where and protect against what?
G6PD → major enzyme of the Pentose Phosphate Pathway (PPP)
G6PD deficiency = partial protection against MALARIA
Which molecules ACTIVATE GLUCONEOGENESIS at high concentrations?
Citrate and Acetyl-CoA
Citrate favors gluconeogenesis
Acetyl-CoA activate pyruvate carboxylase→ promotes gluconeogenesis
The regulatory enzyme of Pentose Phosphate Pathway (PPP) that positively regulated by
NADP+
Because if NADP+ is high, that means the cell needs more NADPH (positively regulated)
When energy is high, G6P is NOT used in which of the following
GLYCONEOGENESIS
Because if the energy is high, you dont need to be breaking anything down
Only broken down if energy is LOW
Which kinds of LIPIDS are found in the plasma membrane of a mammalian cell?
Phospholipids → major membrane lipids
Cerebrosides → glycolipids found in membranes, especially nervous tissue
What is TRUE about PERIPHERAL PROTEINS?
-Interact with lipid head groups through electrostatic interactions AND H bonding
-Can be displaced/dissociated from the membrane by changing ionic strength OR pH
Why does the cell use MULTI-STEP pathways in metabolic reactions?
-Allows for better regulation
-Small amounts of energy can be used or captured in each step
-It allows the cell to respond more rapidly to changing conditions
What are 2 features of glycerophospholipids and sphingolipids that allow them to spontaneously form lipid bilayers in polar solvents?
1) They are AMPHIPATHIC - they have a polar hydrophilic head and nonpolar hydrophobic tails
2) They have large/bulky polar head groups that can interact with each other
Where is CHOLESTEROL likely to be found?
BOTH the outer and inner leaflets
Where is a GANGLIOSIDE more likely to be found?
Outer Leaflet
→has a polar head group
Where is a PHOSPHATIDYLINOSITOL (inositol head groups) likely to be found?
Inner Leaflet
→ has to do with intra signaling, so inside
Plant’s Acyl Chains Fluidity
Low temperatures/Cold = too rigid, stiff
Warm temperatures/Hot= too fluid
PLANTS ADJUST ACYL CHAINS TO COMPENSATE: (want to do opposite)
Low temp= unsaturated, shorter chains
→ kinks stop lipids from packing tightly, shorter chains have weaker interactions = fluid
High temp= saturated, longer acyl chains
→ straight chains pack together more tightly, longer chains have stronger interactions = less fluid and stable
Transport - circulating glucose is low, but glucose concentration INSIDE red blood cells is high
Wants to move out, high to low this is down the gradient
1) out of cell
2) Faciliated = glucose is polar
3) No ATP requ’d
Transport- glucose concentration is high in the small intestine after eating. Glucose concentration INSIDE cells is even higher
tricky, body still wants to absorb glucose from the intestine into the cell so low→high
This is AGAINST the gradient
1)Into the cell
2)Active Transport
3) Yes, ATP requ’d
Transport- after firing, neuron has 100mM Na+ INSIDE, 145mM OUTSIDE. Resting state should be 15mM inside.
There’s too much inside right now, so Na+ needs to move out
Inside to out is Low→ high which is AGAINST the gradient
1) out of cell
2) Active Transport
3) Yes, ATP requ’d
In a CATABOLIC pathway…
Macromolecules are broken down to produce → ATP
The reduced cofactors → NADH/FADH2 (with H)
In an ANABOLIC pathway…
ATP and reduced cofactors → synthesize macromolecules from small, simple precursors
Why is ATP hydrolysis so FAVORABLE?
1) Resonance Stabilized
2) Separation of Negative Charges
3) Increased entropy, produces a lot of particles
Why are thioesters like coenzyme A (CoA) high energy?
They are NOT resonance stabilized, therefore HIGHLY reactive.
What are 2 ways that cells use membranes to regulate pathways (tight regulation)?
1) Compartamentalization
2) Separating/ organizing pathways → separates metabolites, enzymes, substrates
Hexokinases - why is it important for glucose to be phosphorylated once it enters the cell?
Glucose → glucose-6-phosphate = glucose becomes trapped inside the cell and can be committed metabolism (activates it/increases activity)
*It keeps glucose trapped inside the cell as G6P and prepares it for metabolism.
Why does Glycolysis have many advantages over other ATP production pathways, even though it doesn’t produce a lot of of energy?
1) It’s FAST
2) Its anaerobic, so it doesn’t require any oxygen
Enzymes for Glycolysis
Hexokinase, PFK, Pyruvate Kinase
Enzymes for Gluconeogenesis
Glucose-6-Phosphatase, Fructose-1,6-Bisphosphatase, PEPCK, Pyruvate Carboxylase
Enzymes above are reversible. This means…
Delta G is near 0 both directions
Products NEVER accumulate in the cell, how does this drive the overall pathway in the desired direction…
-Product are used IMMEDIATELY
-Drives reactions FORWARD via Le’Chatliers principle (concentrations drive direction)
Cori Cycle - anaerobic conditions, pyruvate is reduced to lactate.
What molecule is oxidized?
NADH is oxidized to NAD+ (via liver)
Why does reduction of pyruvate allow glycolysis to CONTINUE?
NAD+ is generated for glycolysis (via muscle)
What 2 conditions must be met for the cell to activate Gluconeogenesis?
1) Low blood glucose
2) Little to no glycogen left
What does high Citrate activate?
Fructose-1,6-bisphosphatase/ gluconeogenesis
(It inhibits PFK, glycolysis)
What does AMP activate?
PFK / Glycolysis
Because if you have low energy levels, you want to make energy
What does Insulin activate?
Glycogen Synthesis
What does Epinephrine activate ?
Glycogenolysis, breakdown of glycogen
What does Glucagon activate?
Fructose-2,6-bisphosphatase 2/ GLYCONEOGENESIS
-glucagon is only activated in the “starved state”
What does ATP activate?
Gluconeogenesis
Because if you have high amounts of energy then you want to make more energy (can spend the ATP to make glucose)
What does Cortisol activate?
Glycogenolysis
→Stress/emergency situation
Why isnt the Cori Cycle a futile cycle?
It is compartmentalized
Different tissues = separated
Muscle makes lactate
Liver makes glucose
What tissue carries out glycolysis?
Muscle
What tissue/organ carries out gluconeogenesis?
Liver
What self-inflicted activity would cause you to use the Cori Cycle?
Exercise
Insulin and Glucagon
Pancreas
Glucagon is alpha
Insulin is beta
Which transmembrane protein moves one molecule across in one direction?
Uniporter
What is the aerobic fate of pyruvate?
To be turned into Acetyl-CoA
What is the impact of cholesterol on melting temperature?
Broadens the Tm
What lacks the glucose-6-phosphatase enzyme?
Muscle → DOES GLYCOLYSIS
Glucose-6-phosphatase is for gluconeogenesis
→ lacks it so that it cannot release free glucose into the bloodstream and instead uses glucose for its own energy needs
→ wants to keep glucose to itself
What molecule would most likely passively diffuse along its gradient?
Water
How many molecules of ATP if PFK is inhibited?
Zero, because thats the investment phase you aren’t making any then
What is NOT a high energy molecule?
AMP
What kind of lipid is in the plasma membrane of NEURONS?
Sphingolipids
What are signs of OXIDATION?
-More bonds to oxygen
-Fewer bonds with Hydrogen
-More carbon-carbon double bonds
Which hormone OVERRIDES all catabolic pathways, regardless of whether insulin or glucagon is present?
Epinephrine, cause its emergency fuel mobilization so it will override anything
How many sugars are in a ganglioside?
More than 1
Hormone that indicates glucose is GONE?
Glucagon
Which hormone indicates the “fed” state?
Insulin
Why can cholesterol maintain membrane fluidity?
They have a flexible hydrocarbon tail despite it being a bulky rigid molecule
Order of transport from Most to Least fluid (Cholesterol Transport)
ER, Golgi, Plasma membrane
Cholesterol regulates membrane fluidity by:
Increase fluidity:
Prevents close packing of acyl chains
Decrease fluidity:
Forces acyl chains closer together
Lipid-Linked Membrane Protein
Lipid is directly attached to protein and inserts into membrane
Peripheral Membrane Protein
Stuck to surface via interaction with head groups and interactions (electrostatic and H-bonding)
What is ATP used for in Active Transport?
ATP is needed for a conformational change