Final Exam Flashcards
What is metabolism?
Metabolism is the overall process through which living systems acquire and use free energy to carry out their various functions, is traditionally divided into two parts:
Catabolism, how energy is gained from the break-down
Anabolism, how energy is used for biosynthesis
Metabolism are the reactions by which biomolecules are built and broken down
difference between catabolism and anabolism
Anabolism is the building of complex molecules from numerous simple ones. Think of protein synthesis.
Catabolism is the breakdown of complex molecules into numerous simple ones.
is catabolism exergonic or endergonic
In general, catabolic reactions carry out the exergonic oxidation of nutrient molecules. The free energy thereby released is used to drive such endergonic processes as anabolic reactions, the performance of mechanical work, and the active transport of molecules against concentration gradients.Exergonic and endergonic processes are often coupled through the intermediate synthesis of a “high-energy” compound such as ATP.
In an exergonic reaction, energy is released to the surroundings. The bonds being formed are stronger than the bonds being broken. In an endergonic reaction, energy is absorbed from the surroundings. The bonds being formed are weaker than the bonds being broken.
Many of the specific reactions of metabolism are common to all organisms, with variations due primarily to the sources of the free energy that supports them. What are the different metabolic sources of energy?
Autotrophs are organisms that can produce their own food from the substances available in their surroundings using light (photosynthesis) or chemical energy (chemosynthesis).
(a) plants, (b) algae, and (c) certain bacteria.
Heterotrophs cannot synthesize their own food and rely on other organisms — both plants and animals — for nutrition.
An autotroph is an organism that can synthesize their organic molecules from simple inorganic substances. They are producers. A heterotroph is a consumer and it obtains organic molecules from other organisms.
Organisms can be further classified by the identity of?
the oxidizing agent for nutrient breakdown/by their requirement for oxygen
the oxidizing agent for nutrient breakdown/by their requirement for oxygen
Obligate aerobes (which include animals) must use O2, whereas anaerobes employ oxidizing agents such as sulfate or nitrate. Facultative anaerobes, such as E. coli, can grow in either the presence or the absence of O2 . Obligate anaerobes, in contrast, are poisoned by the presence of O2
isozymes
An intriguing manifestation of specialization of tissues and subcellular compartments is the existence of _____, enzymes that catalyze the same reaction but are encoded by different genes and have different kinetic or regulatory properties.
A
isozymes
Different tissues often express different isozymes to match tissue function.
using different forms of the same enzyme to catalyze a given biochemical reaction. These different forms of the same enzyme are known as isozymes or isoenzymes. Isozymes arise from different genes, have different sequences of amino acids and a different structure yet catalyze the same reaction, have different properties and exhibit different enzymes kinetics and are usually controlled by different allosteric effectors.
Energy from oxidation of metabolic fuel is released stepwise. In what form is it stored and made available to drive endergonic processes?
ATP - the primary energy “currency” of the cell.
Why are phosphoanhydride bonds “high-energy”?
- Resonance stabilization of products larger than that of substrates.
- Mutual repulsion of negatively charged groups larger in substrates than in products.
- Smaller solvation energy of phosphoanhydride as compared to hydrolysis products.
Why is ATP so stable, despite the large amount of free energy released by its hydrolysis?
How can you drive an endergonic reaction?
Couple it with an exergonic reaction. Purpose of Coupled Reactions?
A
The hydrolysis of a “high-energy” compound, while releasing considerable free energy, is not in itself a useful reaction. However, the exergonic reactions of “high-energy” compounds can be coupled to endergonic processes to drive them to completion
Inorganic pyrophosphatase function
supply additional “driving force”.
Catalyzes Additional Phosphoanhydride Bond Cleavage by suppling additional “driving force”.
is an enzyme that catalyzes the conversion of one ion of pyrophosphate to two phosphate ions.[1] This is a highly exergonic reaction, and therefore can be coupled to unfavorable biochemical transformations in order to drive these transformations to completion.[2]
Explain how cellular ATP is replenished by phosphagens.
A
utilizes phosphocreatine and ADP to regenerate ATP in the cell when at rest (relies on concentration of substrate and products to determine if reaction should go forward or reverse)
What are thioesters?
“primitive” high-energy compounds
involved in substrate-level phosphorylation
acetyl-coenzyme A (acetyl-CoA)
Phosphocreatine function?
Phosphocreatine provides a “high-energy” reservoir for ATP formation (in muscles, nerves). How is phosphocreatine regenerated?
ATP + creatine –>ADP + phosphocreatine
most common source of energy in organisms? most common electron carriers?
OXIDATION-REDUCTION REACTIONS
“REDOX REACTIONS”
- NAD+ transfers 2 electrons
- FAD transfers one electron
- Fe2+/3+
They accept high energy electrons and carry them ultimately to the electron transport chain where they are used to synthesize ATP molecules
NAD + and FAD are not direct sources of energy, so what do they do?
A
When these electron carrier molecules accept the electrons, they are reduced into and form energy molecules NADH and FADH2
How do redox reactions occur? Loss of electrons is what? Gain of electrons is?
electrons are transferred from electron donor
(reducing agent) to electron acceptor (oxidizing agent)
loss of electrons = oxidation; gain of electrons = reduction
Slides 25-39 Glycolysis reactions
What is homolactic fermentation?
The process in which Under anaerobic conditions in muscle, pyruvate is reduced to lactate to regenerate NAD +
slide 41
What catalyzes the oxidation of NADH by pyruvate to yield NAD+ and lactate.
lactate dehydrogenase (LDH)
This reaction is often classified as Reaction 11 of glycolysis. The lactate dehydrogenase reaction is freely reversible, so pyruvate and lactate concentrations are readily equilibrated.
What is Alcoholic Fermentation?
Alcoholic Fermentation Converts Pyruvate to Ethanol and CO2
In yeast and certain other microorganisms, pyruvate is decarboxylated to yield CO 2 and acetaldehyde, which is then reduced by NADH to yield NAD +and ethanol.
the conversion of pyruvate to ethanol and CO2. to regenerate NAD+ FOR glycolysis
Yeast produces ethanol and CO 2 via what two consecutive reactions?
The decarboxylation of pyruvate to form acetaldehyde and CO 2 as catalyzed by pyruvate decarboxylase (an enzyme not present in animals).
The reduction of acetaldehyde to ethanol by NADH as catalyzed by alcohol dehydrogenase (Section 11-1C), thereby regenerating NAD + for use in the GAPDH reaction of glycolysis.
which needs a cofactor, Alcoholic Fermentation or Homolactic Fermentation?
Alcoholic Fermentation,
TPP Is an Essential Cofactor of Pyruvate Decarboxylase. Pyruvate decarboxylase contains the coenzyme thiamine
pyrophosphate
pyruvate is decarboxylated by a thiamine pyrophosphate (TPP)–dependent mechanism, and the resulting acetaldehyde is reduced to ethanol.
Compare the ATP yields and rates of ATP production for anaerobic and aerobic degradation of glucose.
he rate of ATP production by anaerobic glycolysis can be up to 100 times faster than that of oxidative phosphorylation
But Aerobic yields more ATP 32 per glucose and Fermentation is 2 ATP per glucose
Consequently, when tissues such as muscle are rapidly consuming ATP, they regenerate it almost entirely by anaerobic glycolysis.
What makes Enzymes candidates for flux-control points? Name three
Enzymes that function with large negative free energy changes.
hexokinase-not required when glycogen is source for glycolysis (as often in muscle)
, phosphofructokinase- major control point for glycolysis in muscle
and pyruvate kinase-last reaction of glycolysis
are metabolically irreversible.
Inhibitors and activators of the flux control points
Hexokinase- G6P inhibitor
Phosphofructokinase- ATP inhibitor, Activators- AMP, F2,6P
Pyruvate Kinase- ATP Inhibit, Activator AMP,PEP,FBP
What is the primary flux control point for glycolysis and why?
Phosphofructokinase.
Because when the G6P source for glycolysis is glycogen, rather than glucose, as is often the case in skeletal muscle, the hexokinase reaction is not required.
Pyruvate kinase catalyzes the last reaction of glycolysis and is therefore unlikely to be the primary point for regulating flux through the entire pathway.
Evidently, PFK, an elaborately regulated enzyme functioning far from equilibrium, is the major control point for glycolysis in muscle under most conditions.
What is the pentose phosphate pathway?
What two things do it generate?
alternative pathway to glycolysis
provides NADPH for fatty acids and cholesterol and ribose-5-phosphate for nucleotide biosynthesis (R5P)
difference between glucose and glycogen
Glucose is a single sugar unit or monosaccharide. Glycogen is a multi-sugar unit or polysaccharide
function of glycogen and starch?
Store glucose for metabolic use
Glycogen broken down so it can enter glycolysis
In animals, a constant supply of glucose is essential for tissues such as?
the brain and red blood cells which depend almost entirely on glucose as an energy source
The mobilization of glucose from glycogen stores, primarily in where?, provides a constant supply of how much glucose to all tissues.
liVER
When glucose is plentiful, such as immediately after a meal, glycogen synthesis accelerates. Yet the liver’s capacity to store glycogen is sufficient to supply the brain with glucose for only about half a day. Under fasting conditions, most of the body’s glucose needs are met by what?
gluconeogenesis (literally, new glucose synthesis) from noncarbohydrate precursors such as amino acids.
structure of glycogen and starch? its branched at how many residues
α(1→4)-linked D-glucose with α(1→6)-linked branches every 8–14 (10) residues, highly branched
amylose has no branches
amylopectin has branches every 24-30 residues
in glycogen how are the glucose units removed
glucose units are removed from the nonreducing ends which
allows rapid mobilization of large amounts of glucose
difference between non reducing and reducing end?
reducing end - aldehyde/acetal can be relatively easily oxidized
nonreducing end- not an aldehyde
what is glycogenolysis?
the breakdown of glycogen
List the three enzymes involved in glycogen degradation and describe the type of reactions they catalyze. slide 11-24
1.Glycogen phosphorylase (or simply phosphorylase) catalyzes glycogen phosphorolysis (bond cleavage by the substitution of a phosphate group) to yield glucose-1-phosphate (G1P)
Leaves a limit branch
2. Glycogen debranching enzyme removes glycogen’s branches, thereby making additional glucose residues accessible to glycogen phosphorylase.
Phosphoglucomutase converts G1P to G6P, which has several metabolic fates (
Glucose mobilization in the liver involves a series of conversions from glycogen to glucose-1-phosphate to glucose-6-phosphate and finally to glucose.
difference between glycogen phosphorylase a and b difference between glycogen synthase a and glycogen synthase b
glycogen synthase a dephosphorylated
is more active
glycogen synthase b phosphorylated
is less active
glycogen phosphorylase a at Ser14 is more active
glycogen phosphorylase b is less active it is dephosphrylated
glycogen phosphorylase is activated by phosphorylation (b → a), whereas glycogen synthase is inactivated by phosphorylation (a → b). Conversely, dephosphorylation inactivates glycogen phosphorylase and activates glycogen synthase.
List the three enzymes involved in glycogen synthesis
UDP–glucose pyrophosphorylase, glycogen synthase, and glycogen branching enzyme.
How is glycogen synthesis initiated?
Glycogen synthase only extends existing chains.
Glycogenin
Glycogenin is glycosylated on a Tyr residue by tyrosine glycosyltransferase. Glycogenin can extend chain by up to seven residues, using UDPG.
Glycogen granules consist of 1 molecule glycogen (with up to 120,000 glucose units), 1 molecule of glycogenin, 1 molecule of glycogen synthase, plus other enzymes and regulatory proteins.
Why is glucose stored in form of glycogen?
To avoid “osmotic stress” (high osmotic pressure).
Osmotic pressure is a colligative property, i.e. it is dependent on the number of dissolved particles, not on their properties (such as size).
Concentration of glycogen in liver cell ≈ 10 nM
Concentration of glucose contained in glycogen ≈ 0.4 M
What two enzymes in glycogen synthesis and degradation are under allosteric control and covalent modification?
A
Glycogen Phosphorylase and Glycogen Synthase
Glycogen metabolism is ultimately under the control of hormones such as ?
A
insulin, glucagon, and epinephrine.
What is Gluconeogenesis and where does It occur?
A
necessary when glucose and glycogen supplies are depleted
occurs in liver (and kidney)
When dietary sources of glucose are not available and when the liver has exhausted its supply of glycogen, glucose is synthesized from noncarbohydrate precursors (lactate, pyruvate, and amino acids.) by gluconeogenesis.
pyruvate is converted to glucose.
The 4 noncarbohydrate precursors that can be converted to glucose include?
the glycolysis products lactate and pyruvate, citric acid cycle intermediates, and the carbon skeletons of most amino acids.
What must all the noncarbohydrate precursors convert to very first thing in the reaction? (a citric cycle intermediate)
A
First, however, all these substances must be converted to the four-carbon compound oxaloacetate (at left), which itself is a citric acid cycle intermediate
How is gluconeogenesis related to glycolysis
Gluconeogenesis is mostly the reverse of glycolysis with the pyruvate kinase reaction bypassed by the pyruvate carboxylase and phosphoenolpyruvate carboxykinase reactions, and the phosphofructokinase and hexokinase reactions bypassed by phosphatase reactions.
What is the problem that occurs when trying to synthesize oxaloacetate?
Glycolysis and gluconeogenesis occur in cytosol, oxaloacetate is produced in mitochondrion.
No transporter for oxaloacetate across the inner mitochondrial membrane exists.
Gluconeogenesis Requires Metabolite Transport between Mitochondria and Cytosol.
Route 2 results in transport of reducing equivalents; NADH is used in mitochondrion and produced in cytosol.
Cytosolic NADH is required for gluconeogenesis.
Cytosolic NADH is also generated by lactate dehydrogenase reaction.
Glucogenesis produces how many ATP/mol vs glycolysis
…uses 6 mol ATP/mol glucose…
Glycolysis produces 2 mol ATP/mol glucose.
Other Carbohydrate Biosynthetic Pathways
O-linked oligosaccharides- synthesis in Golgi apparatus.
-attached to Ser, Thr of polypeptide, determined by secondary or tertiary structure
O-Linked oligosaccharides are synthesized by the sequential addition of sugars to a protein.
N-linked oligosaccharides
attached to Asn
N-Linked oligosaccharides are assembled on a dolichol carrier and then transferred to a protein.
Formation of glycosidic bond requires?
nucleotide sugars/energy:
CAC?
-A multistep catalytic process that oxidizes the acetyl group of acetyl-CoA derived from carbohydrates, fatty acids, and amino acids to 2 molecules of CO2 with the concomitant reduction of NAD + and FAD to NADH and FADH2 and the production of GTP. Reduced compounds NADH and FAD conserve the liberated free energy.
-Recovers energy from metabolic fuels/release stored energy
-Pyruvate derived from glucose can be split into CO 2and a two carbon fragment that enters the cycle for oxidation as acetyl-CoA
-Citric acid cycle supplies the reactants for a variety of biosynthetic pathways.
-8 reactions
it accounts for the major portion of carbohydrate, fatty acid, and amino acid oxidation, the citric acid cycle is often considered the “hub” of cellular metabolism.
-Reoxidation of NADH and FADH 2 by O2 during electron transport and oxidative phosphorylation yields H2O and ATP.
One complete round of the citric acid cycle yields?
two molecules of CO2, three NADH, one FADH2 , and one “high-energy” compound (GTP or ATP)
The oxidation of an acetyl group to 2 CO 2requires the transfer of how many electrons?
Where is the free energy of oxidation of the acetyl group conserved in?
Where is energy recovered?
How much ATP are formed when the pairs of electrons eventually transfer to O2?
A
-4 electrons. The reduction of 3 NAD +to 3 NADH accounts for three pairs of electrons; the reduction of FAD to FADH 2 accounts for the fourth pair.
-the reduced enzymes NADH and FADH2
-Energy is also recovered as GTP (or ATP)
-10 ATP
Are the carbon atoms of the two molecules of CO 2produced in one round of the cycle the two carbons of the acetyl group that began the round?
No, These acetyl carbon atoms are lost in subsequent rounds of the cycle. However, the net effect of each round of the cycle is the oxidation of one acetyl group to 2 CO2 .
How Is acetyl-CoA formed?
A
Acetyl-CoA is formed from pyruvate through oxidative decarboxylation by a multienzyme complex named pyruvate dehydrogenase that catalyzes a five-part reaction in which pyruvate releases CO 2 and the remaining acetyl group becomes linked to coenzyme A.
This reaction sequence requires 5 cofactors.
pyruvate dehydrogenase contains multiple copies of what three enzymes/subunits?
A
pyruvate dehydrogenase (E1)
dihydrolipoyl transacetylase (E2)
dihydrolipoyl dehydrogenase (E3)
Pyruvate dehydrogenase (E1), a TPP-requiring enzyme, decarboxylates pyruvate, yielding a hydroxyethyl-TPP carbanion
the hydroxyethyl group is transferred to a lipoamide of E2 (dihydrolipoyl transacetylase)
Hydroxyethyl is oxidized to acetyl and lipoid disulfide is reduced
(transfer of acetyl group to lipoamide)
generating an active E1
This results in the formation of acetyllipoamide
E2 then catalyzes the transfer of an acetyl group from lipoamide to CoA, yielding acetyl-CoA
Acetyl-CoA has now been formed, but the lipoamide group of E2 must be regenerated.
Dihydrolipoyl dehydrogenase (E3) reoxidizes dihydrolipoamide to lipoamide to complete the catalytic cycle of E2. E3 is reduced as a result.
re-oxidation of reduced E3
The sulfhydryl groups are reoxidized by a mechanism in which FAD funnels electrons to NAD+, yielding NADH
E1 is pyruvate dehydrogenase which uses thiamine pyrophosphate (TPP) as a cofactor to decarboxylate pyruvate and transfer the remaining hydroxyethyl fragment to the lipoamide cofactor attached to E2. This results in the formation of acetyllipoamide, equivalent to reduction of lipoamide (and oxidation of the hydroxyethyl fragment), as becomes clear upon subsequent transfer of the acetyl residue to coenzyme A, catalyzed by E2, a acetyltransferase and E3, which regenerates lipoamide from dihydrolipoamide, is dihydrolipoyl dehydrogenase
FAD is reduced by lipoamide
NAD+ is reduced by FADH2
