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Biochem Exam 4 Content (Lec 28-36)

Terms in this set (189)

List the 3 major purposes of living organisms that require a constant input of energy.
muscle contraction, active transport (moving molecules across their gradients), and biosynthesis
Phototrophs vs. Chemotrophs
phototrophs: obtain energy through the capture of sunlight
chemotrophs: obtain energy through oxidation of carbon fuels
Define intermediary, catabolism, anabolism, and amphibolism
intermediary: when the reactants or products of a reaction are interconnected with other reactions
catabolism: combust carbon fuels to synthesize ATP or ion gradient (breaking things down)
anabolism: use ATP and reducing power to synthesize large biomolecules (building things up)
amphibolism: both ana or cata, like the citric acid cycle
An example of an anabolic pathway is _____.

a) smaller amino acids being linked together to make a protein
b) the tendency to gain or lose weight
c) the burning of fat by exercise
d) a protein being broken down into smaller amino acids
a) smaller amino acids being linked together to make a protein
Describe coupled reactions and how they work
when a thermodynamically unfavorable reaction in a pathway can be made to occur by coupling it with a more favorable reaction (the overall G has to be negative when adding the reactions together).
Describe the structure of ATP and how it contributes to its high phosphoryl transfer potential
- resonance stabilization
- electrostatic repulsion (negative charges repel each other but are reduced when hydrolyzed)
- increase in entropy (more disorder, more products)
- hydration stabilization (water binds to ADP and Pi which forms H bonds and high IM forces in products)
What compounds have a higher phosphoryl transfer potential?
all these generate ATP
phosphenolpyruvate, bisphosphoglycerate, & creatine phosphate
How does creatine phosphate serve as a "high energy" buffer in vertebrate muscle?
creatine phosphate can regenerate ATP from ADP, which allows for short bursts of activity; it's a buffer because of its abundance and high phosphoryl-transfer potential relative to that of ATP
substrate-level phosphorylation vs oxidative-level phosphorylation
substrate: the energy of oxidation of GAP (oxidation of glyceraldehyde 3-phosphate to 3-phsphoglyceric acid) is inititally trapped as a high phosphoryl transfer potential compound and used to form ATP
oxidative: the energy of a proton gradient is coupled with ATP synthesis (90% of our ATP is produced by this)-- this is the ETC!!
ATP has a high phosphoryl group transfer potential because...
a) it is chemically unstable
b) it has a high rate of spontaneous hydrolysis at physiological pH and temp
c) it turns into H20 easily
d) it has 3 phosphate groups linked to 3 sulfur groups
e) cleavage of either of its two phosphanhydride bonds proceeds with a large negative delta G of hydrolysis
e) cleavage of either of its two phosphanhydride bonds proceeds with a large negative delta G of hydrolysis
Describe the relationship between the oxidation state of a carbon molecule and its usefulness as fuel.
The more reduced (gaining of electrons) a carbon is, the more free energy (the more negative) is released upon oxidation. Carbon atoms are oxidized to make CO2, and the electrons are accepted by oxygen to form H20.
Why are fats more efficient food sources?
Because they are more reduced.
List the major activated carriers of:
-phosphoryl groups
-electrons for fuel oxidation
-electrons for reductive biosynthesis
-two-carbon fragments
-phosphoryl = ATP
-fuel oxidation = NADH/NAD+ & FADH2/FAD
-reductive biosynthesis = NADPH/NADP+
-two-carbon = coenzyme A
coenzyme A structure and its role as a carrier of acetyl or acyl groups
-is the key intermediate for energy metabolism; acyl group is highly exergonic because thioester bond is unstable
-it is a carrier derived from vitamin pantothenate.
-acyl groups are important in catabolism (oxidation of fatty acids) and anabolism (synthesis of membrane lipids)
Which of the following best characterizes NADH and NADPH?
a) both are interchangeably used for both ATP generation and biosynthesis
b) NADH is used for ATP generation, whereas NADPH is used for biosynthesis
c) NADPH is used for ATP generation, whereas NADH is used for biosynthesis
d) both ATP generation and biosynthesis preferentially use NADH over NADPH
b) NADH is used for ATP generation, whereas NADPH is used for biosynthesis
List the 6 key reactions in metabolism and identify the enzyme class
-oxidation-reduction (oxidoreductases), NAD or FAD
-group transfer (transferases), phosphate groups
-hydrolytic (hydrolases), using H20 to cleave
-cleaving by other means (lyases), no H20 or O2 or ATP
-isomerization (isomerases)
-ligation requiring ATP cleavage (ligases)
List the 3 major mechanisms for regulation of metabolism and give examples
Metabolic processes must be regulated to create homeostasis which is maintained by...
1) controlling the amounts of enzymes (rate of synthesis vs degradation)
2) controlling catalytic activity (ATCase, phosphorylation, hormonal control)
3) controlling the accessibility of substrates (opposing reactions, synthesis vs degradation)
Define energy charge and compare it with phosphorylation potential
high energy charge (1) = lots of ATP, higher chance of donating phosphate
low energy charge (0) = little ATP
-energy charge is buffered.
-phosphorylation potential depends on the concentration of Pi and is directly related to the free energy storage available from ATP
Explain the advantage of having metabolic enzymes in complexes
multienzyme complexes increase catalytic efficiency by sort of creating that domino effect- makes it easier for one product to become a reactant of another reaction
which of the following is NOT one of the requirements for energy use in a cell?
a) muscle contraction
b) biosynthesis
c) compartmentalization
d) active transport
c) compartmentalization
in amphipathic pathways, anabolism and catabolism occur simultaneously or distinctly?
distinctly. You can't build AND break simultaneously, it's one or the other depending on the environment
Order the depletion of energy sources during sustained exercise
1) ATP
2) creatine phosphate
3) anaerobic metabolism
4) aerobic metabolism
_____ are going to be a better energy source because they are more reduced.
fats. They are long chains of H-C, but can only be broken down anaerobically (oxidation)
ion gradients are most commonly found in _________________.
Oxidative phosphorylation; 90% of all ATP production, form of cellular energy that can be coupled with ATP synthesis
NADH and FADH2 are used for ________ while NADP is used for ____________
fuel oxidation, reductive biosynthesis
Name the 4 biomolecules of life
carbs, proteins, lipids, nucleic acids
Explain why carbohydrates and lipids are our preferred metabolic fuels
They can both be reduced which means more energy released.
Fats are a more efficient fuel source than carbs because the carbons in fats are more reduced
Outline the digestion of carbs, fats, and proteins (include enzymes)
Begins in mouth: saliva/alpha amylase begins the digestion of carbohydrates
Stomach: protease pepsin digests proteins
Small intestine: secretin (neutralizes the stomach acid) and CCK (which stimulates the release of digestive enzymes from pancreas)
Define carbohydrate and monosaccharide
carbs: "hydrated carbon"; aldehydes or ketones that contain two or more alcohol groups
mono: simple carbs, aldoses or ketoses that contain two or more alcohol groups
List the common examples of monosaccharides
trioses (3, smallest), pentoses (5), and hexoses (6)
Identify reducing sugars and phosphate-containing sugars
pentoses: riboses
hexoses: glucose, fructose, galactose, and mannose
epimers vs anomers
both are diastereoisomers (not. mirror images, multiple chiral centers)
epimers: differ at one of several asymmetric carbon atoms
anomers: differ at a new asymmetric carbon atoms formed on ring closure
what are maltose, lactose, and sucrose made up of? Which enzymes catalyze these in mammals?
maltose = glucose + glucose
lactose = glucose + galactose
sucrose = glucose + fructose
-maltase, lactase, sucrase
outline the pathway for the conversion of fructose and galactose into glyceraldehyde 3-phosphate and glucose 6-phosphate
...
Describe the biochemical defects in lactose intolerance and galactosemia
lactose: deficiency in lactase
gala: deficiency in a critical transferase in the galactose utilization pathway (more severe)
Describe the structures and biological roles of glycogen, starch, amylose, amylopectin, and cellulose
-animals store glucose as glycogen (branched) while plants store glucose as starch
-two forms of starch: amylose (unbranched) and amylopectin (branched)
-cellulose is tough (like celery) and is hard to digest because of its linkages (favors straight chains)
How is glycogen made and broken down in humans?
Glycogen stores glucose in our tissues, muscles, and liver. Several enzymes participate in carb digerstion: a-amylases, a-dextrinase, a-glucosidase, and maltase. Endogenous glycogen is broken down by glycogelysis
Which of the following is an accurate statement regarding carbs?
a) dihydroxyacetone and glyceraldehyde are both hexoses
b) galactose and mannose are both ketoses
c) glycogen and starch are both homopolymers of glucose
d) lactose and sucrose are both monosaccharides
e) ribose and fructose are both pentoses
c) glycogen and starch are both homopolymers of glucose
Difference between saturated and unsaturated fatty acids
saturated: no double bonds, all H's present
unsaturated: double bonds present
Explain the relationship between fatty acid chain length and degree of saturation and the physical property of the melting point
-unsaturated fatty acids (double bonds) have lower melting points than do saturated fatty acids of the SAME length
-short chain length and the presence of cis double bonds enhance the fluidity of fatty acids
-more doubles = more fluidity, more rigid = more hydrophobic
Give the roles of fatty acids and triacylglycerols
-fuel molecules stored as triacylglycerols (where three fatty acids are esterified to one molecule of glycerol)
-fatty acids are components of phospholipids and glycolipids
-attached to proteins to localize the proteins in membranes
-function as hormones and intracellular messengers
Outline how dietary triacylglycerols are digested and absorbed into the tissues
-form "lipid droplets" into the stomach inserted by bile salts (via gall bladder). This makes them more accessible by lipases (enzyme to digest lipids) which is secreted by the pancreas.
-carried as micelles to the intestinal epithelium cells for absorption
-reformed and packaged into lipoprotein particles called chylomicrons to travel through the blood so that its absorbed by tissues
Outline how endogenous tracylglycerols are broken down by lipolysis to glycerol and fatty acids
1) TAGs are degraded to fatty acids and glycerol, which are released from the adipose tissue and transported to energy-requiring tissues via lipolysis
2) fatty acids must be activated and transported to mitochondria for degradation
3) Fatty acids broken down into acetyl Co-A which is then processed in citric acid cycle
State the fates of glycerol and fatty acids after mobilization
fatty acids: aren't soluble in water so they bind to the blood protein albumin, which delivers them to tissues in need for fuel
glycerol: absorbed by the liver and phosphorylated, then is an intermediate in both glycolytic and glunoeogenic pathways
Define glycolysis
-sequence of reactions that metabolizes 1 molecule of glucose to 2 molecules of pyruvate with a net of 2 ATP
-process is anaerobic (no oxygen)
Why is glycolysis considered an anaerobic pathway?
it is believed that it evolved before substantial amounts of oxygen were in the atmosphere
Why is glucose a prominent fuel in many organisms?
-For mammals, it's the ONLY fuel the brain uses under non-starvation conditions and the ONLY fuel RBCs can use at all
-it can form under prebiotic conditions
-most stable hexose
-low tendency to nonenzymatically react with proteins
Outline the use and storage of dietary glucose.
-insulin is released by pancreas to enable glucose to enter cells for energy
-leftover glucose in blood is stored as fat as triglycerides or fatty adipose tissue
-muscles and liver take as much glucose and store as glycogen
-brain and RBCs take glucose as energy
Compare and contrast the 5 GLUT transporters in animals
GLUT's 1-5: facilitate the movement of glucose across the cell membrane
GLUT's 1-3 are insulin-independent
GLUT 4 is insulin-dependent
GLUT 5 is in the small intestine and involves fructose
describe the purpose behind the use of insulin in GLUT4 function
4 is insulin dependent. It's what senses the glucose in tissues and regulates whether glucose enters the cell or not
State the overall reaction of glycolysis
trapping glucose in the cell, modifying it so that it's cleaved into a pair of phosphorylated 3-carbon compounds, oxidizing them to pyruvate + 2 net ATP
Why are glycolytic enzymes associated in complexes?
because they increase catalytic efficiency so that it's easier for one product to become the reactant of the next reaction
compare and contrast the energy investing stage and energy harvesting stage of glycolysis + order steps
investment: trap glucose, modify it, and cleave into pair
harvesting: oxidize cleaved compounds, create pyruvate and ATP
1)trap 2)modify 3)cleave into pair 4)oxidize pair 5)create pyruvate & 2 ATP
Rate determining step of glycolysis and explain why it's irreversible
F-6P to F-1, 6-BP using phosphofructokinase (PFK1). It is tightly regulated and is irreversible because ATP is used as a reactant which has a high phosphoryl transferase that cannot be reached in reverse
kinetically "perfect" enzyme in glycolysis, describe its mechanism, name its intermediate, and its toxic derivative
-triose phosphate isomerase (TPI) which means it takes place every time the enzyme and substrate meet
-it suppresses an undesired side reaction by keeping its active site closed until the product is formed
-endiol intermediate to a toxic product, methyl glyoxyl (this is the side reaction it suppresses)
Outline how fructose and galactose enter the glycolytic pathway
They are both converted into glycolytic intermediates
fructose: in the liver, it's metabolized by fructose 1-phosphate pathway; in other tissues, it's directly phosphorylated by hexokinase
galactose: is converted into glucose 6-phosphate by the galactose-glucose interconversion pathway
1) glucose --> glucose 6-phosphate
Hexokinase, ATP to ADP, irreversible
2) glucose 6-phosphate --> fructose 6-phosphate
phosphoglucose isomerase, reversible
3) fructose 6-phosphate -> fructose 1,6-bisphosphate
phosphofructokinase, ATP to ADP, irreversible
4a) fructose 1,6-bisphosphate --> glyceraldehyde 3-phosphate
aldolase
4b) fructose 1,6-bisphosphate --> dihydroxyacetone phosphate
triose phosphate isomerase, reversible
5) glyceraldehyde 3-phosphate --> 1,3-biphosphoglycerate
glyceraldehyde 3-phosphate dehydrogenase, Pi, NAD+ to NADH, reversible
6) 1,3-biphosphoglycerate --> 3-phosphoglycerate
phosphoglycerate kinase, ADP to ATP, reversible
7) 3-phosphoglycerate --> 2-phosphoglycerate
phosphoglycerate mutase, reversible
8) 2-phosphoglycerate --> phosphoenolpyruvate
enolase, H20 comes out
9) phosphoenolpyruvate --> pyruvate
pyruvate kinase, ADP to ATP, nonreversible
explain how the cori cycle, glucose-alanine cycle, and glycerol fuels gluconeogenesis
Lactate produced by muscle during contraction is released into the blood. Alanine is released from the breakdown of proteins to amino acids. The liver removes the lactate and alanine and converts them into glucose, which can be released into the blood.
explain why the 3 irreversible steps in glycolysis must be bypassed in gluconeogenesis
so that glycolysis and gluconeogenesis don't occur simultaneously (only one direction is active)
What is meant by a substrate cycle?
each bypass in the gluconeogenesis route is called a substrate cycle
How many ATP equivalents are needed to produce one molecule of glucose from 2 molecules of pyruvate?
it's a cost of 4 ATP equivalents already in the anabolic pathway
Explain why and how glycolysis is regulated differently in the skeletal muscle vs the liver
Since the role of these tissues differ, the regulation will differ slightly
muscle: glycolysis here provides ATP primarily to power contraction
liver: has more biochemical functions so it's more complicated. Maintains the blood-glucose concentration
Why is fructose 2,6-bisphosphate a key allosteric regulator of glycolysis and gluconeogenesis?
it stimulates phosphofructokinase and inhibits fructose 1,6-bisphosphatase. It is produced and degraded in response to blood-glucose levels
Pyruvate + CO2 + ATP + H2O ---> oxaloacetate + ADP + Pi + 2H+
pyruvate carboxylase, irreversible
oxaloacetate + GTP ---> phosphoenolpyruvate + GDP + CO2
phosphoenolpyruvate carboxykinase
fructose 1,6-biphosphate + H20 ---> fructose 6-phosphate + Pi
fructose 1,6-biphosphatase
glucose 6-phosphate + H20 --> glucose + Pi
glucose 6-phosphatase
Which enzyme is reversible?
a) hexokinase
b) pyruvate kinase
c) phosphofructoskinase-1
d) fructose 1,6-biphosphatase
e) phosphophenolpyruvate carboxykinase
e) phosphophenolpyruvate carboxykinase
gluconeogenesis is the synthesis of _________ from __________ and ________________.
the synthesis of glucose from pyruvate and other non carb precursors
gluconeogenesis mainly takes place in the...
liver
what are the major precursors of gluconeogenesis?
amino acids, glycerol, and lactate
True or False
glycerol enters the pathway without modification
false, glycerol needs to be turned into DHAP
gluconeogenesis is utilized especially in times of....
starvation, because the brain and RBCs need glucose
Compare and contrast the fermentation of glucose with complete oxidation of glucose in terms of energy production
Glycolysis is anaerobic and involves one glucose making 2 pyruvate + 2 ATP. Pyruvate can be further processed anaerobically into lactate or ethanol. But under aerobic conditions, pyruvate can be completely oxidized to CO2 which generates much more ATP
Explain why NAD+ needs to be regenerated after glycolysis and explain how fermentations and cellular respiration accomplish that
Since there are limited amounts of NAD+, it must be regenerated for glycolysis to proceed. It is regenerated by further oxidation of pyruvate to CO2 (cellular respiration), or by formation of ethanol or lactate from pyruvate (fermentation).
Define fermentation
anaerobic ATP generating pathway in which electrons are removed from one organic compound and passed to another organic compound
Define obligate anaerobes and facultative anaerobes
*types of fermentation*
obligate: organisms that cannot survive in the presence of O2
facultative: organisms that metabolize glucose aerobically when oxygen is present and perform fermentation when oxygen is absent
pyruvate --> acetaldehyde
pyruvate decarboxylase, CO2, irreversible
acetaldehyde ---> ethanol
alcohol dehydrogenase, NAD+, reversible
pyruvate --> lactate
lactate dehydrogenase, NAD+, reversible
Why can't cells continuously use the breakdown of glucose to pyruvate to generate energy without further conversion of pyruvate via fermentation or respiration?
a) the rate of energy production by glycolysis alone is too slow for cells' biochemical reactions
b) the amount of energy produced by glycolysis alone is insufficient to fuel cell growth
c) the amount of inorganic phosphate available becomes limiting
d) the electron acceptor reduced during glycolysis much be regenerated
e) the complete breakdown of pyruvate is necessary tp produce the carbon dioxide needed by cells
d) the electron acceptor reduced (NAD+) during glycolysis much be regenerated
Describe the Cori cycle and explain its importance to glucose homeostasis
The cycle of gluconeogenesis in the liver and that of glycolysis in the muscles. In glycolysis, glucose is made into pyruvate which can be further made into lactate; lactate can be used in gluconeogenesis to make pyruvate and then to glucose.
Describe aerobic glycolysis (Warburg effect) and explain why this type of glycolysis is preferred in fast growing cells (tumors) and during exercise
a process of obtaining ATP by metabolizing glucose to lactate even in the presence of oxygen. Because tumors can grow faster than blood vessels, aerobic glycolysis allows growth in the absence of oxygen since they tend to grow in hypoxic environments. Therefore, aerobic glycolysis makes them less dependent on oxygen
During normal aerobic cellular respiration in mammals, pyruvate is most likely oxidized to ______ while the aerobic glycolysis, such as what happens in tumor cells, pyruvate is converted to_______.
a) acetylaldehyde; ethanol
b) acetyl CoA; glyceraldehyde
c) acetyl CoA; lactate
d) acetylaldehyde; lactate
e) acetyl CoA, glyceraldehyde
c) acetyl CoA; lactate
List the three enzymes and five coenzymes that make up the pyruvate dehydrogenase complex and describe each of their roles
E1: pyruvate dehydrogenase component, it catalyzes decarboxylation of pyruvate combined with TPP
E2: dihydrolipoyl transacetylase, it catalyzes the transfer of the acetyl group to coenzyme A to form acetyl CoA
E3: dihydrolipoyl dehydrogenase, it catalyzes the reoxidation of dihydrolipoamide and also regenerates NADH
coenzymes: thiamine pyrophosphate, lioic acid, FAD, CoA, and NAD+
Difference between catalytic and stoichiometric coenzymes and list which coenzymes fall under them
catalytic: (self explanatory); thiamine pyrophosphate, lipoic acid, and FAD
stoichiometric: cofactors that function as substrates; CoA and NAD+
--> TPP is an activated carrier of aldehyde, lipoic acid and CoA are activated carriers of acyl groups, FAD and NAD+ are activated carriers of electrons
Describe the ways that the pyruvate dehydrogenase complex is regulated and explain why it's regulated
it is tightly regulated because of the formation of acetyl CoA from pyruvate is irreversible in animal cells. Allosteric control, hormone control, reversible covalent modification, and energy status
Which activated carrier is NOT found in the PDH complex?
a) lipoic acid (lipoamide)
b) thiamine pyrophosphate (TPP)
c) NAD+/NADH
d) FAD/FADH2
e) ATP
e) ATP
Outline the catabolic and anabolic purposes of the citric acid cycle
catabolic: harvesting of high energy electrons from carbon fuel
anabolic: using citric acid cycle intermediates to make more complex molecules
Describe the two stages of the citric acid cycle
1st stage: citric acid cycle where two carbons are introduced by condensation of an acetyl group with oxaloacetate (4C's); 6 carbon citrate forms and undergoes two oxidative decarboxylations = 2 CO2's
2nd stage: oxaloacetate is regenerated
oxaloacetate ---> citrate
citrate synthesis,
H20 + acetyl CoA to CoA
(ligase)
citrate ---> isocitrate
aconitase
(lyase)
isocitrate---> a-ketoglutarate
isocitrate dehydrogenase,
NAD+ to NADH + CO2
(oxidoreductase)
a-ketoglutarate ---> succinyl CoA
a-ketoglutarate dehydrogenase complex,
NAD+ + CoA to NADH + CO2
(oxidoreductase)
succinyl CoA ---> succinate
succinyl CoA synthetase,
ADP + Pi to ATP + CoA
(ligase)
succinate ---> fumarate
succinate dehydrogenase,
FAD to FADH2
(oxidoreductase)
fumarate ---> malate
fumarase,
H20 goes in
(lyase)
malate ---> oxaloacetate
malate dehydrogenase,
NAD+ to NADH + H+
(oxidoreductase)
outline the steps of the citric acid cycle in terms of numbers of carbons in intermediates
...
Why are enzymes of the citric acid cycle assembled in complexes?
this close arrangement of enzymes enhances efficiency of the cycle by substrate channeling (a reaction product passing from one active sight to another via channels)
Why is there a physical link between the citric acid cycle and the ETC?
succinate dehydrogenase?
Why is O2 required for the citric acid cycle to function?
because NAD+ and FAD can only be regenerated in the mitochondria by the transfer of electrons to O2
How many ATP equivalents are generated by the complete oxidation of fructose?
30 ATP (which is the same as complete oxidation of glucose and galactose)
How is the citric acid cycle regulated?
control points = isocitrate dehydrogenase and a-ketoglutarate dehydrogenase complex
high energy charge = inhibits those enzymes (ATP)
low energy charge = activates enzymes (ADP)
How are the citric acid cycle intermediates replenished after anabolic use?
anaplerotic reactions (filling the intermediates back up); catalyzed by pyruvate carboxylase
high energy charge = oxaloacetate is converted into glucose
low energy charge = oxaloacetate replenishes the citric acid cycle
Describe the glyoxylate cycle found in plants and some bacteria and explain why animals cannot store carbons from fat as sugars, but plants and some bacteria can
glyoxylate cycle is similar to citric acid cycle but bypasses the two decarboxylation steps, allowing synthesis of carbs from fats. Succinate can be converted into oxaloacetate and then into glucose in only plants/some bacteria
Describe the 3 stages in which endogenous triacylglycerols are catabolized
1) degradation of TAG to release fatty acids and glycerol into the blood for transport to tissues
2) activation of fatty acids and transport into the mitochondria for oxidation
3) degradation of fatty acids to acetyl CoA for processing by the citric acid cycle
Free fatty acids are released from the adipocytes after mobilization of fat stores by:
a) pancreatic lipases
b) proteases
c) alpha amylase
d) hormone stimulated lipases
e) nucleases
d) hormone stimulated lipases
Describe the 4 repeated steps of fatty acid oxidation and synthesis
oxidation, hydration, oxidation, and cleavage
1) fatty acid is oxidized to introduce a double bond
2) double bond is hydrated to introduce an OH group
3) alcohol is oxidized to a ketone
4) fatty acid is cleaved by coenzyme A to yield acetyl CoA and a fatty acid chain two carbons shorter
Explain why the degradation of unsaturated & odd-chain fatty acids requires additional steps
because beta-oxidation alone cannot degrade unsaturated fatty acids
- cis-enoyl CoA isomerase is required
Describe the synthesis (anabolism) and degradation (catabolism) of ketone bodies and explain where they will be synthesized and degraded
synthesis: acetoacetate formed by hydroxymethylglutaryl CoA cleavage enzyme; D-3-hydroxybutyrate formed by reduction of acetoacetate vy D-3-hydroxybutyrate dehydrogenase; acetone is a waste product generated by the spontaneous decarboxylation of acetoacetate (all in the liver)
degradation:
outline fatty acid synthesis (anabolism) and list the key intermediates
-begins in cytoplasm, all enzymes are in a single polypeptide (giant enzyme) aka fatty acid synthase
-reductant = NADPH
-ends in mitochondrial matrix for degradation
-oxidants = NAD+ and FAD
-enzymes are distinct
How many ATP equivalents are produced when D-3-hydroxybutyrate is completely oxidized to H20 and CO2?
22.5 ATP
(1 NADH x 2.5 ATP + 2 acetyl CoA x 10 ATP = 22.5 ATP)
Describe the committed step of fatty acid synthesis and explain how it is controlled and how the control mechanisms also control fatty acid degradation
-ACC (acetyl CoA carboxylase) is essential in regulating fatty acid synthesis and degradation-- it catalyzes the committed step in fatty acid synthesis: the production of malonyl CoA
Describe the structure and function of the mitochondrion in regard to energy metabolism
-eukaryotic oxidative phosphorylation takes place in the mitochondria which depends on electron transfer
-mitochondria are bounded by double membrane
--> intermembrane space between the outer and inner membranes, where oxidative phosphorylation takes place; folded into ridges called cristae which is impermeable to most molecules
--> matrix, bounded by inner membrane where most reactions of citric acid and fatty acid oxidation
--> outer mitochondrial membrane is permeable to most small ions and molecules bc of protein mitochondrial porin
Describe the meaning of redox potential for redox couple
measure of a molecule's tendency to donate or accept electrons (E'0)
relate free energy to redox potentials
a strong reducing agent (the one getting oxidized) readily donates electrons and has a -E, while a strong oxidizing agent (the one getting reduced) readily accepts electrons and has a positive E'
how much ATP can NADH and FADH2 fuel?
1 NADH = 2.5 ATP
--> NADH has a higher negative E
1 FADH2 = 1.5 ATP
List the names of all 4 enzyme complexes and the non-enzymatic components of the ETC
1: NADH-Q oxidoreductase, NADH to NAD+, 4 protons are simultaneously pumped out of the mitochondrial matrix
2: succinate-Q reductase, FADH2 to FAD, is the physical link between citric acid and ETC, NOT a proton pump
3: Q-cytochrome c oxidoreductase, cytochromes b and c1, heme, 4 protons are pumped
4: cytochrome c oxidase, ends with O2 as final electron acceptor; 4 protons used to reduce oxygen, 4 protons pumped into intermembrane space
Describe the flow of electrons from NADH to O2 and compare that with FADH2 to O2-- which pathway pumps more protons and why?
the reduction potential of NADH is much more negative than FADH2, therefore it is more likely to donate its electrons to O2 (which readily accepts electrons) than FADH2. That is why it can create more ATP.
explain how the Q cycle functions electrons from a two-electron carrier to a one-electron carrier and how it pumps protons
QH2 carries 2 electrons, c carries only 1. 1 electrons from QH2 reduces c and one reacts with Q to form Q-. Another QH2 reduces c and Q-
1 cycle = 4 protons pumped out + 2 additional ones removed from matrix
Explain how cytochrome c oxidase catalyzes the reduction of O2 to water and at the same time pumps protons into the im space
cytochrome c oxidase accepts 4 electrons from four molecules of c in order to catalyze the reduction of O2 to H2O. Eight protons are removed from the matrix, four of them are used to reduce oxygen, and an additional 4 are pumped into the IM space.
Which of the following enzyme complexes catalyzes the reduction of O2 to H2O during oxidative phosphorylation?
a) ATP synthase
b) cytochrome c oxidase
c) NADH-Q oxidoreductase
d) Q-cytochrome c oxidoreductase
e) succinate-Q reductase
b) cytochrome c oxidase
benefits of having an ETC located in a membrane
proton pumps pump ions into the im space which creates a gradient, which is used to catalyze the creation of ATP.
Why is the ETC assembled in a large complex called respirasome?
it forms a circular structure with two copies of each complex 1 and 4 surrounding two copies of complex 3. The structure allows for complex 2 to associate in a gap between complexes 1 and 4-- this also enhances enzyme efficiency
Describe why reactive oxygen species (ROS) can result during cellular respiration and explain how antioxidants prevent damage by the ROS
ROS occurs when there is a partial reduction of O2 creating reactive oxygen derivatives. Superoxide dismutase (SOD), catalase, glutathione peroxidase, and a few vitamins are antioxidant enzymes that can help protect against ROS damage
Which of the following is NOT an electron acceptor in the mitochondrial respiratory chain?
a) FMN
b) FAD
c) O2
d) NAD+
e) CoQH2
e) CoQH2
Describe the proton-motive force and the chemiosmotic hypothesis and explain how experiments using bacteriorhodopsin helped to support the hypothesis
-the movement of protons down a concentration gradient to produce ATP
-synthetic vesicles containing bacteriorhodopsin and mitochondrial ATP synthase; when vesicles were exposed to light, ATP was formed therefore it is clear that the respiratory chain and ATP synthase are biochemically separate systems linked only by a proton force
Describe the components of the ATP synthase and their roles (structure and function)
proton conducting (F0) = embedded in the inner mitochondrial membrane and contains proton channel
catalytic unit (F1) = contains three active sites located on three beta subunits, protrudes into the mitochondrial matrix, encodes catalytic activity
stator = stays in place, alpha subunit plays role of how proteins come around
headpiece = alpha and beta active sites, catalytic
rotor = c subunit, gamma spins
Describe the binding-change mechanism that leads to the release of tightly bound ATP from ATP synthase
three catalytic beta subunits of the F1 component can exists in three conformations:
-O (open) = nucleotides can bind to or be released from the beta subunit
-L (loose) = nucleotides are trapped in the beta subunit
-T (tight) = ATP is synthesized from ADP to Pi
*every spin = 1 ATP*
Rotation of the ______ subunit causes the _______ subunit to change from tight conformation where ATP is produced to open conformation where ATP is released
gamma, beta
Describe the experiments that were used to demonstrate that ATP synthase is the World's smallest rotor
-use of single-molecule techniques where they demonstrated the rotation using cloned alpha3beta3gamma subunits
-beta subunits were engineered to contain His tags which have a high affinity for Ni atoms
-addition of ATP caused it to rotate counterclockwise
Explain how proton flow around the c ring powers ATP synthesis and describe the relationship between number of c rings and amount of protons
*flow occurs through F0*
-protons enter the half-channel and bind to aspartate residue on one of the subunits of the c ring, and then leave the c subunit once they rotate around
-each 360 turn of the gamma subunit = 3 ATP
-the force of the proton gradient powers the rotation of the c ring; the rotation of the c ring powers the movement of the gamma subunit which in turn alters the conformation of the beta subunits
-the less c, the less amount of protons needed to be used
describe carbohydrate transport
-pyruvate is made in the cytoplasm so it has to be shuttled to the mitochondria
-oxaloacetate is the opposite
-shuttles: malate dehydrogenase isozymes and malate transporter
describe lipid transport
-fatty acid synthesis is in the cytoplasm while fatty acid degradation is in the mitochondria, therefore acetyl CoA must be shuttled back and forth
-shuttles: citrate and pyruvate shuttles
describe how electrons from cytoplasm NADH are shuttled
they're carried across the mitochondrial matrix via glycerol 3-phosphate (tissues) and malate-aspartate shuttles (heart and liver)
describe how NADH from the cytoplasm is transported
glycerol 3-phosphate shuttle carries it to the ETC for its electrons to be transferred to FADH2 and then from Q to QH2
Explain why complete oxidation of glucose leads to approx 30 ATP
26 ATP from oxidative phosphorylation, 4 ATP per two pyruvate in glycolysis, 2 ATP per glucose in fermentation, and 2 ATP using malate aspartate shuttle
Explain how oxidative phosphorylation is largely controlled by the need of ATP and why oxygen consumption is used to assess function of oxidative phosphorylation
electrons do NOT flow through the ETC unless ADP is available to be converted into ATP. Oxygen consumption is a measure of ETC and oxidative phos. since it will allow both to continue at a high rate until the substrates are depleted
Describe non-shivering thermogenesis and explain why this process results in heat production
when the ETC is uncoupled from ATP synthesis, heat is generated. This is most frequent in adults in the BAT tissue which is rich in the mitochondria.
Describe how the ETC and oxidative phosphorylation can be inhibited
-inhibition of complex 1 by preventing the generation of the proton motive force
-inhibition of ATP synthase in complex 2
-uncoupling of ETC function from ATP synthase in complex 4
-inhibition of ATP export/inport
*the close you get to oxygen, the more toxic it'll become*
Outline the major catabolic, anabolic, and amphibolic pathways
1) carbs metabolism
- glycolysis (cat)
- gluconeogenesis (ana)
2) lipid metabolism
- lipolysis (cat)
- triacylglycerol synthesis (ana)
- fatty acid degradation (cat)
- fatty acid synthesis (ana)
- ketone body degradation (cat)
- ketone body synthesis (ana)
3) amino acid metabolism
- amino acid degradation (cat)
- amino acid synthesis (ana)
4) citric acid cycle (amphi)
5) oxidative phosp. (cat)
outline how all the major catabolic, anabolic, and amphibolic pathways are interconnected via their intermediates
glucose: glycolysis and gluconeogenesis
pyruvate: glycolysis and gluconeogenesis
acetyl CoA: beta-oxidation, fatty acid biosynthesis, citric acid cycle, and ketone body biosynthesis
fatty acids: beta-oxidation and fatty acid biosynthesis
Where do the major pathways of metabolism occur?
cytosol: glycolysis, fatty acid biosynthesis, some steps of gluconeogensis
mitochondrion: beta-oxidation, citric acid cycle, first steps of gluconeogensis, ketone body synthesis, and ETC
Role of the liver
- metabolic hub of the body
- maintains fuel
- glucose regulator
-- HIGH: removes excess glucose from the blood to store it as glycogen (when carbs are high too)
-- LOW: provides glucose and ketone bodies to other tissues and break down glycogen
Role of the skeletal muscle
- prefers glucose as fuel
- proteins in muscle can be used as energy source in times of starvation (amino acids)
- lactate and alanine are exported into the blood for substrates for gluconeogensis in the liver or kidney
-- REST: uses fatty acids and glucose
-- ACTIVE: uses all available fuels to produce ATP
Role of cardiac muscle
*aerobic only*
- relies on fatty acids as fuel and requires oxygen to maintain blood flow
- no storage
-- LOW glucose: uses ketone bodies as fuel
Role of adipose tissue
- stores fat for future use
- prefers to use fatty acids and glucose as fuel
- secretes leptin (fullness) to regulate metabolic homeo
Role of stomach
- digestion of metabolic fuels
- secretes gastrin (acid) and ghrelin (hunger) that control eating behaviors through neural signaling in the brain
Role of small intestine
- absorbs most nutrients getting its digestive enzymes from the pancreas
- secretes CKK (releases hydrolases like lactase, mutase, maltase, and amylase) and secretin-- both control eating behaviors through neural signaling in the brain
Role of large intestine
- absorbs water and electrolytes
- secretes glucagon-like peptides 1 & 2 and PYY
- gut bacteria
Role of pancreas
- secretes metabolic hormones as well as digestive enzymes
- secretes insulin in response to rising glucose levels in the blood
- secretes glucagon in response to low glucose levels in the blood
Role of kidney
- secretes toxic metabolites
- carry out gluconeogensis
- makes glucose using amino acids
Role of the brain
- is unable to store or export energy
- depends on glucose since 60% of the body's glucose is required by the brain
- can use ketone bodies during starvation
Outline the metabolic flux between the key metabolic tissues
*metabolic flux between tissues optimizes use of stored energy*
1) liver serves as a metabolic hub of the body and coordinates the exchange of metabolites between major tissues and organs
2) brain requires constant input of glucose (energy drain)
3) cardiac muscle mostly relies on fatty acids to optimize ATP production
4) the exchange of fatty acids and triacylglycerol between the adipose tissue and the liver is in the triacylglyerol cycle
5) skeletal muscle uses glycogen stores and fatty acids as fuel and contributes to glucose production via the cori cycle
6) amino acids are cycled with glucose in the alanine-glucose cycle
Which vital organ acts as the metabolic hub for the human body?
a) pancreas
b) liver
c) kidney
d) muscle
e) stomach
b) liver
Compare and contrast the effects of insulin, glucagon, and epinephrine on metabolic pathways
insulin: secreted by pancreatic beta cells when blood glucose levels are high/carbs. Insulin stimulates glucose uptakes in the liver, skeletal muscle, and adipose tissue. It also activates glycogen and fatty acid synthesis
glucagon: secreted by pancreatic alpha cells when blood-glucose levels are low. It stimulates gluconeogenesis, glycogen degradation, and fatty acid export from adipose tissue when food is not available. It has no effect on skeletal muscle or brain.
epinephrine: released by adrenal medulla in response to low blood glucose levels and/or stress. It reacts with second messenger systems in a variety of tissues
Which of the following is adipokine that inhibits food intake?
a) ghrelin
b) CKK
c) leptin
d) insulin
e) GLP-1
c) leptin
Insulin is released from pancreatic beta cells in response to ____ blood glucose
a) low
b) high
b) high
Explain how hormones regulate expression of genes controlling metabolism and how energy homeostasis is maintained using AMPK signaling and mTOR signaling.
The CREBS cycle is an example of a resident nuclear transcription factor
AMPK: activated when energy charge of the cell is low
mTOR: activated under nutrient rich conditions
Explain how AMPK acts as the cell's fuel gauge, specifically explaining which pathways are regulated by AMPK and why
activates catabolic pathways that generate ATP: promotes glycolysis, glucose uptake, and fatty acid oxidation
inhibits anabolic pathways to conserve ATP more vital processes: inhibits fatty acid synthesis and glycogen synthesis
Which pathway below would be activated by AMPK signaling?
a) gluconeogenesis
b) fatty acid synthesis
c) glycogen synthesis
d) glycolysis
d) glycolysis
Define metabolic homeostasis
the ability to maintain adequate but not excessive energy stores-- energy balance. If fuels are consumed in excess, it is stored.
Define energy balance
the measure of caloric homeostasis
Define body mass index
a way to determine whether an individual is overweight or obese, its weight divided by height
List the overlapping possible explanations for the current obesity epidemic
-our bodies are programmed to store excess calories as fat in case food becomes scarce
-leaner individuals may have avoided predation, but since that barely exists now, leanness has declined
-highly palatable foods can act as drugs by creating a stimulating reward pathway
-changes in our gut microbiome may cause an accumulation of excess calories
-genetic differences alter how individuals respond to obesity inducing environmental conditions
-access to food is easy to come by
Describe how leptin may be a contributing factor to obesity
leptin resistance may be a contributing factor. It may result from the inappropriate activation of proteins called SOCS which bind to phosphorylated tyrosine residues and disrupt the signal-transduction pathway
Explain the thrifty gene hypothesis and relate it to obesity
States that individuals with a capacity to store extra fat during times of feast survive longer during times of famine. There are people who can be related genetically but have completely different diets which determines their different weights, despite their genes being almost alike
Hypothesize as to why most fad diets do not work
Diets aren't as effective because they tend to be pretty restrictive that people break off easily and end up gaining more weight
Differentiate between 'good' and 'bad' fats
"good" fats: polyunsaturated fatty acids and cis fats, lots of double bonds
"bad" fats: saturated fatty acids and trans fats
Define glycemic index
measure of the amount of glucose that enters the blood as a function of time and uses pure glucose as the standard. Foods with a glycemic index of <55 are healthy carbs because the effects on blood glucose levels are less dramatic
Difference between insulin-dependent (type 1 diabetes) and non-insulin dependent (type 2 diabetes). Explain what likely causes both types, what the implications are of both, and common treatments
1: caused by a deficiency of pancreatic beta cells and is usually treated with daily insulin injections
2: usually caused by insulin resistance, which is a deficiency in signal transduction. Specific drugs can treat this.
Diabetes mellitus type ____ is an autoimmune response that destroys pancreatic beta cells and type ____ occurs due to insulin resistance. In both types, the liver responds by synthesizing ____ glucose.
a) II, I, more
b) II, I, less
c) I, II, more
d) I, II, less
e) I, II, the same amount of
c) I, II, more
Describe metabolic syndrome and what it can lead to if not treated or managed
Caused by a lifestyle of prolonged positive energy imbalance (energy going IN). Symptoms are abdominal obesity, insulin resistance, hypertension, hyperlipidemia, and high risk for cardiovascular disease. It predisposes patients for type 2.
Describe the metabolic alterations that take place during acute and chronic starvation
acute: proteins are degraded and the carbon skeletons are used as gluconeogenic precursors
chronic: liver begins to form large amounts of ketone bodies. Gluconeogenesis depletes the supply of oxaloacetate, which is essential for the entry of acetyl CoA into the citric acid cycle. Ketone bodies become the main source of fuels. Once protein degradation starts to occur (which is the last resort), death is inevitable.
One of the metabolic adaptations that occurs with prolonged starvation is the increased production of ________ because there is insufficient oxaloacetate for oxidation of all the acetyl CoA produced from fat breakdown.
a) glucose
b) fatty acids
c) amino acids
d) ketone bodies
e) lactate
d) ketone bodies
Describe cachexia and outline the possible causes of it
-alteration of metabolic rate independent of food intake: disconnect in a metabolic feedback loop, disconnection to the loss of appetite. Disconnections lead to an increase in metabolic rate
-elevated levels of cytokines (signaling molecules of the immune system); leads to loss of skeletal muscle mass, muscles burn more energy
Outline the steps of alcohol metabolism
ethanol is metabolized in the liver. This leads to an excess of NADH and acetyl CoA. Excess NADH causes hypoglycemia and lactic acidosis and inhibits fatty acid degradation. Excess acetyl CoA results in increased fatty acid synthesis as well as increased ketone body production
Which redox enzyme is NOT affected by NADH concentration?
a) glyceraldehyde 3-phosphate dehydrogenase
b) pyruvate dehydrogenase complex
c) isocitrate dehydrogenase
d) alpha-ketoglutarate dehydrogenase
e) succinate dehydrogenase
e) succinate dehydrogenase
--> it uses FAD as an oxidant instead of NAD+
Explain how exercise can benefit our metabolism and possibly reverse or prevent metabolic disorder.
Calcium is released during muscle contraction which is a second messenger to activate signaling pathways that stimulate mitochondrial biogenesis. Increased mitochondrial biogenesis and increased fatty acid oxidation present insulin insensitivity. Exercise also activates AMPK signaling.
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