MCC111 CHAPTER 15:METABOLISM Flashcards
Organisms that obtain energy from sunlight.
Phototrophs
Organisms that obtain energy from oxidation of carbon fuels.
Chemotrophs
Refers to all the defined pathways in the cell.
Intermediary metabolism
Metabolic pathway that transforms fuel molecules into energy.
Catabolic pathways
Metabolic pathway that uses energy to synthesize new molecules.
Anabolic pathways
What defines a favorable/unfavorable reaction?
favorable-negative free energy values
unfavorable-positive free energy values
Metabolic pathways frequently contain reactions with positive free-energy values, yet the reactions still take place. How is this possible?
A reaction with a positive free-energy value can be coupled with a reaction with a negative free-energy value to get a negative net free energy value.
The universal currency of free energy that contains two phosphoanhydride bonds–high energy bonds.
ATP
What products result from the hydrolysis of ATP?
Adenosine Diphosphate or adenosine monophosphate
(ADP or AMP)
In cell conditions, what is the energy of hydrolysis?
~50 kJ/mol
Under standard conditions, ATP hydrolysis can change the equilibrium by a factor of __.
-electrostatic repulsion
-resonance stabilization
-stabilization by hydration
Name three compounds that are higher in energy than ATP.
-phosphoenolpyruvate (PEP)
-1,3-bisphosphoglycerate
-creatine phosphate (CP)
What makes ATP a good constituent/carrier for many reactions?
ATP has high free energy that can shift equilibrium of a reaction, but not so high that it can’t be resynthesized when it’s needed.
What provides the energy for generation of ATP?
Oxidation of glucose and fats to CO2.
True or False: Oxidation of carbon compounds occurs at one step on all carbon atoms.
False - oxidation occurs one carbon at a time.
What is carbon oxidation energy used to generate?
high-phosphoryl-transfer potential or an ion gradient
Which generates more energy, carbohydrates or fatty acids, and why?
fatty acids because they are in a more reduced form than carbohydrates are.
True or False: Oxidation occurs directly.
False
Why doesn’t oxidation occur directly?
Rather than taking one highly exergonic reaction, the cell undergoes several reactions as a way to capture the electrons and energy as efficiently as possible.
What are activated carriers for catabolism?
NADH and FADH2
What are activated carriers for anabolism?
NADPH
What is an activated carrier of two carbon unites?
Coenzyme A (CoA)
How many electrons and hydrogen atoms can FAD accept?
2 e-
2 H+
How many electrons and hydrogen atoms can NAD+ accept?
2 e-
1 H+
In oxidation reactions with NAD+, what is usually released?
1 H+
When CoA is linked to two carbon unit, what is it called?
Acetyl CoA
What reactive group in CoA makes transfer of acetyl group exergonic?
Thioester (-SH)
What is true about carriers and evolution?
Carriers are highly evolutionarily conserved–same carriers used in all organisms.
What is the vitamin precursor for carriers, NADH and NADPH?
Nicotinate (niacin)
What is the vitamin precursor for carrier, FADH2?
Riboflavin (vitamin B2)
What is the vitamin precursor for carrier, CoA?
Pantothenate
What are the three principal means of controlling metabolic processes?
- amount of enzyme
- catalytic/enzymic activity
- accessibility of substrates
Why is energy charge of cell important?
It allows many processes to be coordinated with how much energy the cell has or needs.
Fill in the blanks:
Free energy is released from compounds with ____ redox potential to compounds with ___ redox potential.
high redox potential to low redox potential
Cellular energy currency
ATP
Anabolic electron carrier
NADP+
converts light energy into chemical energy
Phototroph
catabolic electron carrier
NAD+
what reaction transfers electrons
oxidation-reduction reaction
activated carrier of two-carbon fragments
Coenzyme A
precursor to coenzymes
vitamins
requires energy
anabolism
used in anabolism and catabolism
amphibolic reaction
yields energy
catabolism
What factors account for the high phosphoryl-transfer potential of nucleoside triphosphates?
- Charge repulsion
- resonance stabilization
- increase in entropy
- stabilization by hydration
Why does it make good sense to have a single nucleotide, ATP, function as the cellular energy currency?
Having only one nucleotide function as the energy currency of the cell enables the cell to monitor its energy status.
Why is ATP usually associated with magnesium or manganese ions?
These divalent ions bind to the negatively charged oxygen atoms found on the phosphoryl groups and help stabilize the charges on ATP.
The standard free energy of hydrolysis for ATP is −30.5 kJ mol−1 (−7.3 kcal mol−1): What conditions might be changed to alter the free energy of hydrolysis?
Increasing the concentration of ATP or decreasing the concentration of cellular ADP or Pi (by rapid removal by other reactions, for instance) would make the reaction more exergonic. Likewise, altering the Mg2+ concentration could raise or lower the dG of the reaction
What is the direction of each of the following reactions when the reactants are initially present in equimolar amounts? Use the data given in Table 15.1.
(a) ATP + H2O ⇌ ADP + Pi
(b) ATP + glycerol ⇌ glycerol 3−phosphate + ADP
(c) ATP + pyruvate ⇌ phosphoenolpyruvate + ADP
(d) ATP + glucose ⇌ glucose 6−phosphate + ADP
Reactions in parts a and c, to the left; reactions in parts b and d, to the right
What information do the ΔG°′ data given in Table 15.1 provide about the relative rates of hydrolysis of pyrophosphate and acetyl phosphate?
None whatosever
- Consider the following reaction.
ATP + pyruvate ⇌ phosphoenolpyruvate + ADP
(a) Calculate ΔG°′ and K′eq at 25°C for this reaction by using the data given in Table 15.1.
(b) What is the equilibrium ratio of pyruvate to phosphoenolpyruvate if the ratio of ATP to ADP is 10?
- (a) ∆G°′ = 31.4 kJ mol−1 (7.5 kcal mol−1) and K′eq = 3.06 × 10^-6
(b) 3.28 × 10⁴
15.13 Calculate ΔG°′ for the isomerization of glucose 6-phosphate to glucose 1-phosphate.
What is the equilibrium ratio of glucose 6-phosphate to glucose 1-phosphate at 25°C?
15.13 ∆G°′ = 7.1 kJ mol−1 (1.7 kcal mol−1).
The equilibrium ratio is 17.8
15.14 The formation of acetyl CoA from acetate is an ATP-driven reaction: Acetate + ATP + CoA ⇌ acetyl CoA + AMP + PPi
(a) Calculate ΔG°′ for this reaction by using data given in this chapter.
(b) The PPi formed in the preceding reaction is rapidly hydrolyzed in vivo because of the ubiquity of inorganic
pyrophosphatase. The ΔG°′ for the hydrolysis of PP i is
−19.2 kJ mol−1 (−4.6 kcal mol−1). Calculate the ΔG°′ for the overall reaction, including pyrophosphate hydrolysis. What effect does the hydrolysis of PPi have on the formation of acetyl CoA?
15.14 (a) Acetate + CoA + H+ goes to acetyl CoA + H2O, ∆G°′ = +31.4 kJ mol-1 (+7.5 kcal mol−1).
ATP hydrolysis to AMP, ∆G°′ = 45.6 kJ mol−1 (−10.9 kcal mol−1).
Overall reaction, ∆G°′ = -14.2 kJ mol−1 (-3.4 kcal mol−1).
(b) With pyrophosphate hydrolysis, ∆G°′ = −33.5 kJ mol−1 (-8.0 kcal mol−1).
Pyrophosphate hydrolysis dramatically increases the exergonicity of the reaction.
15.16 What is the structural feature common to ATP, FAD, NAD⁺, and CoA?
ADP
15.18 What are the activated electron carriers for catabolism?
For anabolism?
15.18 NADH and FADH₁ are electron carriers for catabolism;
NADPH is the carrier for anabolism.
Thioesters, common in biochemistry, are more unstable (energy rich) than oxygen esters. Explain.
The electrons of the C=O bond cannot form resonance structures with the C−S bond that are as stable as those that they can form with the C−O bond. Thus, the thioester is not stabilized by resonance to the same degree as is an oxygen ester.
Glycolysis is a series of 10 linked
reactions that convert one molecule of glucose into two molecules of pyruvate with the concomitant synthesis of two molecules of ATP (Chapter 16). The ΔG°′ for this set of reactions is −35.6 kJ mol−1 (−8.5 kcal mol−1), whereas the ΔG° is −90 kJ mol−1 (−22 kcal mol−1). Explain why the free-energy release is so much greater under intracellular conditions than under standard conditions.
Recall that ∆G = ∆G°′ + RT ln [products]/[reactants]. Altering the ratio of products to reactants will cause ∆G to vary. In glycolysis, the concentrations of the components of the pathway result in a value of ∆G greater than that of ∆G°′.
Examine the pairs of molecules, and identify the more reduced molecule in each pair.
(A) Ethanol or Acetaldehyde?
(B) Lactate or Pyruvate?
(C) Succinate or Fumarate?
(D) Oxalosuccinate or Isocitrate?
(E) Malate or Oxaloacetate?
A, Ethanol; B, lactate; C, succinate; D, isocitrate; E, malate
A multibranched polysaccharide of glucose that serves as a form of energy storage in humans, animals, and fungi. The polysaccharide structure represents the main storage form of glucose in the body.
Glycogen
A peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose in the bloodstream.
Glucagon
Pyruvate is the final product.
Glycolysis
Glucose 6-phosphate is produced in the 1st step.
Glycolysis
Glucose 6-phosphate is the initial reactant.
Glycogenesis
UDP is involved
Glycogenesis
Glucose 6-phosphate is the final product.
Glycogenolysis
This occurs when brain & muscle cells need immediate energy.
Glycogenolysis
Glucose is the final product.
Gluconeogenesis
CO2 is involved.
Gluconeogenesis
True or False:
The PFK-1 reaction in heart tissue does not reach equilibrium.
True
True or False:
In heart tissue, the PFK-1 reaction will be driven toward product formation.
True
Whis step in glyconeogenesis is the main negative control point?
Step 8
fructose 1,6-bisphosphate → fructose 6-phosphate
(Pi is removed)
What inhibits the enzyme in step 8 of the liver?
insulin
AMP (or cAMP)
fructose 2,6-bisphosphate
______ is the predominant isozyme in the liver & has distinct kinetic properties from the other hexokinase isozymes.
Hexokinase IV
(Glucokinase)
Glucosekinase
(Hexokinase IV)
- subcellular localization is regulated by fructose 6-phosphate
- Km is in the range of physiologic blood glucose levels
- not sensitive to inhibition by glucose 6-phosphate
- plans an important role in liver regulation of blood glucose level
Hexokinase I, II, or III
- when blood glucose levels fall below normal range, isozyme remains at max velocity
- when blood glucose is low, will cause cells to trap glucose by phosphorylation
- will be saturated by normal blood glucose concentration
All hexokinase isozymes (I-IV)
will spophorylate several hexoses including glucose
What is the most significant allosteric regulator of PFK-1 (Phosphofructokinase-1?
Fructose 2,6-bisphosphate, which strongly activates the enzyme
(Citrate & ATP inhibit)
_____ is a regulator of both glycolysis and gluconeogenesis for the phosphofructokinase reaction of glycolysis and the fructose 1,6-bisphosphatase reaction of gluconeogenesis.
Fructose 2,6-bisphosphate
In turn, the concentration of ______ is regulated by many hormones, second messengers, and enzymes.
Fructose 2,6-bisphosphate
Increased levels of fructose 2,6-bisphosphate,
Activate glycolysis &
Inhibit gluconeogenesis
Inhibition of Fructose 2,6-bisphosphatase (FBPase-2).
Activate glycolysis &
Inhibit gluconeogenesis
Inhibition of PFK-2.
Activate gluconeogenesis &
Inhibit glycolysis
Increased levels of cAMP.
Activate gluconeogenesis &
Inhibit glycolysis
Increased glucagon levels.
Activate gluconeogenesis &
Inhibit glycolysis
Pyruvate kinase is allosterically inhibited by ______.
ATP
(acetyl-CoA & long-chain fatty acids)
When low blood glucose causes glucagon release, ______-dependent protein kinase phosphorylates the L isozyme of pyruvate kinase, inactivating it.
cAMP
[activating pyrucate carboxylase & PEP carboxykinase]
How does pyruvate kinase differ in the liver &all other glycolytic tissues (muscle)?
liver:
1. PP removes Pi (activates)
2. ATP is used when glucagon levels increase & bind to PKA (cAMP -dependent protein kinase) (inactivates)
tissue:
1. accumulation of fructose 1,6-bisphosphate triggers its activation
2. inhibited by ATP, acetyl-CoA, and long-chain fatty acids
3. alanine, which can be synthesized from pyruvate in one step, allosterically inhibits pyruvate kinase
How is the mechanism in the liver useful?
prevents the liver from consuming glucose by glycolysis when blood glucose concentration is low
(liver exports glucose)
Muscle is not a gluconeogenic tissue because it lacks ______.
Glucose 6-phosphatase
Glucagon secretion is stimulated when blood glucose concentration ______.
Decreases
Which carbohydrate pathways does glucagon stimulate in liver?
gluconeogenesis
glycogenolysis
Epinephrine is released in response to stress, and is a “fight-or-flight” hormone. Which metabolic pathways does epinephrine stimulate?
- lipolysis in adipose tissue
- glycolysis in muscle
- gluconeogenesis in liver
- glycogenolysis in liver and muscle
When blood glucose is ______, the pancreas releases glucagon, a peptide hormone which stimulates the liver to produce and excrete glucose.
Low
How does glucagon stimulation affect the concentration or activity of the following signaling intermediates and enzymes?
increases:
adenyl cyclase
[3’,5’-cyclic AMP]
protein kinase A
fructose 2,6-bisphosphatase
phosphorylase b kinase
glycogen synthase kinase
decreases:
phosphofructokinase-2
[fructose 2,6-bisphosphate]
Glucagon stimulates which pathways?
glycogenolysis
gluconeogenesis
Glucagon stimulation decreases which pathway enzymes?
glycogen synthase
pyruvate kinase (step 10)
phosphofructokinase-1 (step 3)
The enzyme ______ ______ removes terminal glucose residues from glycogen by cleaving α(1,4) linkages.
glycogen phosphorylase
Enzyme activity stops when the enzyme reaches a point ______ glycose residues from a branch point, which is an α(1,6) linkage.
4
The ______ activity of the debranching enzyme moves three glucose residues to another branch, connecting them by an α(1,4) linkage.
Transferase
The ______ activity of the debranching enzyme removes the glucose at its α(1,6) linkage.
Glucosidase
The enzyme ______ ______ continues removing terminal glucose residues.
glycogen phosphorylase
glycogen phosphorylase
What is the reasoning behind carbohydrate loading?
Excess glucose is stored as muscle or liver glycogen, which can be broken down to supply energy during the event.
______ is a positive allosteric modulator of pyruvate carboxylase and a negative modulator of pyruvate dehydrogenase, through stimulation of a protein kinase that inactivates the dehydrogenase
Acetyl-CoA
Another control point in gluconeogenesis is the reaction catalyzed by FBPase-1 (Fructose 1,6-bisphosphatase), which is strongly inhibited by ______.
AMP
______ promotes glycogen degradation and glycolysis by activating glycogen phosphorylase.
AMP
The special role of liver in maintaining a constant blood ______ level requires additional regulatory mechanisms to coordinate glucose production and consumption.
glucose
When the blood glucose level ______, the hormone glucagon signals the liver to produce and release more glucose and to stop consuming it for its own needs.
decreases
The hormonal regulation of glycolysis and gluconeogenesis is mediated by ______ _______________, an allosteric effector for the enzymes PFK-1 and FBPase-1.
fructose 2,6-bisphosphate
Fructose 2,6-bisphosphate ______ PFK-1 and stimulates glycolysis in liver and, at the same time, inhibits FBPase-1, thereby slowing gluconeogenesis.
Activates
cAMP activates cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the bifunctional protein _____/_____.
PFK-2/FBPase-2
Insulin has the ______ effect, stimulating the activity of a phosphoprotein phosphatase that catalyzes removal of the phosphoryl group from the bifunctional protein PFK-2/FBPase-2, activating its PFK-2 activity, increasing the level of fructose 2,6-bisphosphate, stimulating glycolysis, and inhibiting gluconeogenesis.
opposite
Glycogen Synthase Is Also Regulated by ______ & ______
Phosphorylation and Dephosphorylation
