Block 1 Flashcards
what do enzymes increase
speed of reaction
what type of molecule are most enzymes
proteins
what is an apoenzyme
enzyme without its co-factor
non functional
a cofactor that is tightly bound to the enzyme is called what
prosthetic group
cofactors that are complex organic molecules are called what
coenzymes
what are isoenzymes
same enzyme, different structure
what is a zymogen
an inactive enzyme that must be cleaved to become active
what are 2 examples of zymogens
trypsin and chymotrypsin
what are the 4 basic steps of enzyme catalyzed reactions
- binding of substrate
- formation of enzyme substrate complex
- conversion of substrate to product
- release of product from active site
the active site of an enzyme is composed of the __ site and the __ site
catalytic and substrate binding
what does the induced fit model tell
interaction of substrate with enzyme induces conformational changes so the binding is a better fit
what do enzymes reduce
activation energy
what is the transition state for enzymes
peak of energy curve where reactants convert to products
what is involved in catalysis by bond strain
rearrangement when enzyme is bound to substrate induces strain
what is involved in covalent catalysis
formation of a covalent intermediate
what is an example of a covalent intermediate in covalent catalysis
serine proteases
what amino acids make up the serine protease triad
histidine
serine
glutamate (or aspartate)
co-enzymes are often what
water soluble vitamins
increased transcription of a gene or decreased proteolysis of enzyme protein increases or decreases enzyme activity
increases
effect of temperature on enzyme activity
too high= denature
too low= slow down
pH effect on enzyme activity
too high or low= denature
what is Km
the substrate concentration at 1/2Vmax
small Km means high or low enzyme affinity for substrate
high
high enzyme affinity means high or low substrate concentration
low
what do oxido-reductases do
transfer H+ or e-
what do hydrolases do
cleave bonds by addition of water
what do transferases do
transfer a group (not hydrogen or oxygen) from one molecule to another
what do isomerases do
interconvert isomers
what do lyases do
alter bonds without addition of water
what do ligases do
link 2 molecules
what is hydrolysis
bond cleavage by addition of water
what do racemases and epimerases do
interconvert optical isomers
what do dehydrogenases do
remove H
what does the y intercept represent in lineweaver burk plots
1/Vmax
what does the x intercept represent in lineweaver burk plots
-1/Km
what are 3 classifications of reversible inhibitors
competitive
noncompetitive
uncompetitive
where does the inhibitor bind in competitive inhibition
active site
where does the inhibitor bind in noncompetitive inhibition
allosteric site (changes shape)
where does the inhibitor bind in uncompetitive inhibition
enzyme-substrate complex
what effect does competitive inhibition have on Vmax and Km
Vmax unchanged
Km increases
what is an example of a competitive inhibitor in the citric acid cycle
malonate with succinate for succinate dehydrogenase
what is an example of a drug that is a competitive inhibitor
viagra
what effect does noncompetitive inhibition have on Vmax and Km
Vmax decreases
Km unchanged
what type of reversible inhibition can be reversed by increasing substrate concentrations
competitive inhibition
what effect does uncompetitive inhibition have on Vmax and Km
both decrease
what is an example of an uncompetitive inhibitor used to treat manic depression
lithium
what effect does irreversible inhibition have on Vmax and Km
Vmax decreases
Km unchanged
*same effects as reversible noncompetitive inhibition
irreversible inhibition has the same effects on Vmax and Km as what type of reversible inhibition
noncompetitive
what is an example of a toxin that is an irreversible inhibitor
cyanide
how does cyanide act as an irreversible inhibitor
binds to cytochrome oxidase and inhibits complex IV of ETC
what is an example of an irreversible inhibitor type of drug
aspirin
how does aspirin work
inhibits cyclo-oxygenase (COX) –>decreased pain and inflammation
what is an example of a reversible inhibitor drug that acts in the same way as aspirin
ibuprofen
what is an example of an allosterically regulated protein
PFK-1
what does phosphatase do
removes phosphate
what are the usual sites for phosphate addition to proteins (3 amino acids)
serine
threonine
tyrosine
does phosphorylation of glycogen phosphorylase activate or inactivate glycogen utilization
activates
does phosphorylation of glycogen synthase inhibit or activate glycogen synthesis
inhibit
what is enthalpy
amount of heat absorbed or released
what is the symbol for enthalpy
delta H
in endothermic reactions, are reactants or products at a higher energy level
products
are endothermic reactions anabolic or catabolic
anabolic
what does bioenergetics describe
transfer and utilization of energy
do catabolic or anabolic reactions release heat
catabolic
what is the standard free energy for each of the 2 terminal phosphates that ATP can release
-7.3 for each
what is Gibbs free energy
energy available to do work
what do negative delta G^0’ tell
it is an exergonic reaction proceeding to the right (to lower energy state)
spontaneous
what do positive delta G^0’ tell
it is an endergonic reaction proceeding to the left (to lower energy state), nonspontaneous
phosphorylation of glucose by ATP is catalyzed by what 2 enzymes
hexokinase and glucokinase
what is involved in reaction coupling
product of one reaction is the reactant of another
what is the common intermediate compound in coupled reaction in living cells
ATP
how can all sugars be activated
by adding a nucleotide
what is reduction potential a measurement of
the tendency for a substrate (reactant) to accept electrons
how can the proportions of NAD+ and NADH in a solution be determined
UV absorption spectra
a high value at 340nm in UV absorption tells us there is high or low NADH content
high
how is UV spectrophotometry used for lactate dehydrogenase
pyruvate–>lactate, NADH is consumed= decrease in absorbance at 340nm
lactate–>pyruvate, NADH is produced= increase in absorbance at 340nm
why is ATP called a high energy phosphate compound
it has a large negative standard free energy value (-7.3 for each of the 2 terminal phosphates)
what are the 3 main sources of phosphate for ATP
- oxidative phosphorylation
- glycolysis (phosphoglycerate kinase and pyruvate kinase)
- citric acid cycle (succinate thiokinase)
what 2 processes does oxidative phosphorylation couple
respiration and generation of ATP
how does the inner mitochondrial membrane differ from the outer
outer is permeable
inner is impermeable
what is needed due to the impermeability of the inner mitochondrial membrane
transporters
what is the function of cristae of the inner mitochondria membrane
increase SA
where does the electron transport chain occur in the cell
inner mitochondrial membrane
what is the role of the respiratory chain of the mitochondria
conversion of food energy to ATP
what is the basis of the ETC
high energy molecules (ex: glucose) are metabolized by redox reactions to yield CO2 and water
what do the metabolic intermediates of ETC reactions donate electrons to
NAD+ and FAD to form NADH and FADH2
as electrons are passed down the ETC, do they gain or lose free energy
lose
what is the energy lost by electrons as they are passed down the ETC used for
creating a proton gradient
what processes does oxidative phosphorylation couple
electron transport with ATP synthesis
what is the remainder of the free energy not trapped as ATP in the ETC used to drive
calcium transport into mitochondria
generate heat
how many complexes make up the inner mitochondrial membrane
5
what complexes of the inner mitochondrial membrane are used in the ETC
1-4
what are the 2 mobile electron carriers used in the ETC
co-enzyme Q
cytochrome c
what is the final e- acceptor of the ETC
molecular O2
what process accounts for the body’s use of the greatest amount of oxygen
ETC
what is complex 5 of the inner mitochondrial membrane also called
ATP synthase
what complex of the inner mitochondrial membrane catalyzes ATP synthesis
5
what complexes of the inner mitochondrial membrane do e- pass through
1, 3, and 4
what is complex 1 of the inner mitochondrial membrane also called
NADH-Q oxidoreductase
what occurs in complex 1 of the inner mitochondrial membrane
e- are transferred from NADH to CoQ
what is CoQ also referred to as
ubiquinone
what is CoQH2 also known as
ubiquinol
what is complex 3 of the inner mitochondrial membrane also called
Q-cytochrome c oxidoreductase
what does complex 3 of the inner mitochondrial membrane do
pass e- from CoQ to cytochrome c
what is complex 4 of the inner mitochondrial membrane also called
cytochrome c oxidase
what does complex 4 of the inner mitochondrial membrane do
pass e- to O2, causing it to be reduced to H2O
what is complex 2 of the inner mitochondrial membrane also called
succinate-Q reductase
why are e- passed to Q through complex 2 instead of 1
the substrate (succinate) has a greater redox potential then NAD+/NADH
NADH carries a free protein. In the ETC, where is this proton transferred to
NADH dehydrogenase in complex 1
what complexes of the ETC contain iron-sulfur proteins
1, 2, 3
all members of the ETC are proteins with the exception of __ which is a __
coenzyme Q
lipid
coenzyme Q in the ETC accepts e- from what 2 complexes
1 and 2
coenzyme Q can accept e- from what enzyme in glycolysis
glycerophosphate dehydrogenase
coenzyme Q can accept e- from what enzyme in fatty acid oxidation
acyl CoA dehydrogenase
cytochromes contain a __ group with iron in a +__ (2 or 3) state
heme
3+
what complex of the ETC contains copper
4
what is the importance of copper in complex 4
required for splitting of O2
complex 4 contains how many heme and how many copper groups
2 heme
2 copper (CuA and CuB)
how many protons are pumped in complex 1 of the ETC
4
how many protons are pumped in complex 2 of the ETC
none
with the proton gradient of the ETC, the matrix side of the mitochondrial becomes positive or negative
negative
what does the chemiosmotic theory explain
free energy generated by the transport of electrons in ETC is used to produce ATP from ADP+Pi
what complexes of the ETC pump electrons
1, 3, 4
what drives the mechanism of ATP synthetase
proton motive force by electrochemical potential difference due to impermeability of inner mitochondrial membrane
what complexes act as a proton pump, creating a proton gradient across the membrane
I, III, IV
what does ATP synthase convert
ADP+Pi–>ATP
is ATP synthase embedded in the inner mitochondrial membrane or mobile
embedded
what are the 2 components of ATP synthase structure
F0
F1
where is F0 of ATP synthase located
inner mitochondrial membrane
where is F1 of ATP synthase located
mitochondrial matrix
what are the subunits of F1 of ATP synthase
3 alpha, 3 beta
what subunit of F1, alpha or beta, does ADP attach to
beta
what subunit of F1, alpha or beta, does ATP attach to
alpha
one rotation of ATP synthase produces how many ATP
3 (due to having 3 beta subunits)
what makes up the F0 subunit of ATP synthase
C protein subunits
what subunit is attached to the C protein subunits of ATP synthase directly
gamma
what subunit of ATP synthase, alpha beta or gamma, rotates
gamma
what does ATP synthase produce
ATP and heat
what is the function of heat produced by ATP synthase
maintain body temperature
what is the purpose of the ATP/ADP antiporter
as soon as ADP enters and produces ATP, ATP exits
what controls the rate of respiration (ETC/oxidative phosphorylation)
availability of ADP
what are 2 examples of substrate level phosphorylation
glycolytic reactions
citric acid cycle
for each mole of substrate oxidized by complexes I, III, and IV in respiratory chain (ETC) via NADH, how many moles of ATP are produced
2.5
for each mole of substrate oxidized by complexes II, III, and IV in respiratory chain (ETC) via FADH2, how many moles of ATP are produced
1.5
what allows molecular oxygen (O2) to act as an efficient final e- acceptor
high electronegativity
does each step of the ETC have a positive or negative delta G
negative
why is having a -delta G in each step of the ETC important
free energy is created and made available to to work and movement of protons
what do uncouplers do to the ETC
increase permeability of the membrane to ions/create a channel, interfering with the proton gradient as H+ is allowed to pass without going through ATP synthase (no ATP synthesis)
what is the main result of uncouplers of the ETC
energy is released as heat (excess of body heat)
what type of protein does thermogenin act as
uncoupling
is thermogenin a physiological or pathological uncoupler
physiological
where is thermogenin found
brown fat, especially in newborns
what is the function of themogenin
production of body heat
is 2,4-dinitrophenol a physiological or pathological uncoupler
pathological
what class does 2,4-dinitrophenol belong to
uncouplers
how does 2,4-dinitrophenol act
reduces electrochemical potential and short-circuits ATP synthase, causing energy to be released as heat rather than used to synthesize ATP
what is the result of 2,4-dinitrophenol in regards to heat production
hyperthermia
what class of proteins does high dose asprin and other salicylates act as in the ETC
uncouplers
oxidative phosphorylation uncoupling agents __ (increase or decrease) proton gradient and produce heat
decrease
electron transport inhibitors __ (increase or decrease) proton gradient
decrease
ATP synthase inhibitors __ (increase or decrease) proton gradient
increase
what class of antibiotic is oligomycin
macrolide
what is the effect of oligomycin
binds to F0 of ATP synthase, closing the H+ channel and preventing re-entry of protons
e- transport is stopped so no ATP or heat is produced
do uncoupling agents act on a specific complex
no
what complex do Rotenone and metformin act on
I
what complex do antimycin A and dimercaprol (BAL) act on
III
what complex does H2S, Azide, Cyanide, and CO act on
IV
what complex does oligomycin act on
ATP synthase (complex V)
what is Rotenone, which acts on complex I, also referred to as
fish poison
insecticide
what complex do barbiturates (Amytal) act on
I
what complex does malonate inhibit
II
how does cyanide stop ETC
binds Fe3+ and prevents conversion to Fe2+
*oxygen does not bind to Fe3+
how does CO stop ETC
binds Fe2+ and inhibits release of e- to oxygen
what is a common sign of cyanide and CO poisoning
cherry red colored skin (hypoxia)
how to identify cyanide exposure rather than CO
presence of smoke
soot in mouth and nose
odor of bitter almonds
what are 2 treatments for cyanide poisoning
nitrite (best)
hydroxocobalamin
how to identify CO poisoning rather than cyanide
obstructed exhaust
power outages
patients in a group/household with similar symptoms
how does atractyloside inhibit oxidative phosphorylation
inhibits transporter of ADP into ATP
what causes fatal infantile mitochondrial myopathy and renal dysfunction
absence of oxidoreductases of ETC (ATP synthesis) due to error in mitochondrial DNA
what causes MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke)
complex I or complex IV deficiency due to mutation in mitochondrial DNA
how is mitochondrial DNA (mtDNA) inherited
through mother
what is the cause of Leber hereditary optic neuropathy
mutation in mtDNA
what is the cause of Leigh syndrome
a mutation in oxidative phosphorylation
carbohydrates are primarily composed of what 3 elements
C, O, H
how much energy does 1 gram of carbohydrate provide
4cal
what are the most abundant dietary source of energy
carbohydrates
what 2 cells are mostly dependent on carbohydrates are their energy source
brain cells
RBC
what is the energy storage form of carbohydrates
glycogen
what are amino sugars
a monosaccharide in which one or more hydroxyl groups are replaced by amino groups
chemically, carbohydrates are defines as ___ or ___
polyhydroxyl aldehydes or ketones
what are 2 examples of monosaccharides
glucose
fructose
what are 3 examples of dissacharides
lactose
sucrose
maltose
what are 3 examples of polysaccharides
starch
glycogen
cellulose
what is a monosaccharide
sugars that can’t be hydrolyzed into simpler carbohydrates
(absorbable after digestion)
why is glucose identified as an aldose
it contains an aldehyde group
why is fructose identified as a ketose
it contains a ketone group
what are isomers
compounds with the same chemical formula but different structure
why are fructose, glucose, mannose, and galactose all considered isomers
they have the same chemical formula C6H12O6 but a different structure
what are epimeres
isomers that differ around only 1 specific carbon
what is an example of a C4 epimer
glucose and galactose
what is an example of a C2 epimer
glucose and mannose
what are stereoisomers
compounds with the same structural formula but different spatial arrangement
what are enantiomeres
structures which are mirror images of one another
what is an example of an enantiomer
D-glucose and L-glucose
what is considered the reference carbohydrate when looking at structural arrangement
glyceraldehyde
naturally occurring monosaccharides in humans are in L or D confirmation
D
what are anomers
structures that differ around carbon 1 (anomeric C)
__ and __ are used for anomers which are concerned with carbon __
alpha and beta
1
epimers are concerned with carbon __
2, 3, or 4
enantiomers are concerned with carbon __
5
what does dextrose mean
glucose in solution
why is glucose in solution referred to as dextrose
it is dextrorotary (based on rotation of light)
what bond links monosaccharides
glycosidic
what are disaccharides
sugars that yield 2 molecules of monosaccharide (same or different) following hydrolysis
lactose produces what 2 molecules following hydrolysis
glucose
galactose
sucrose produces what 2 molecules following hydrolysis
glucose
fructose
what is the storage form of carbohydrates in humans
glycogen
what are the 2 main components of starch
amylose
amylopectin
what bonds make up amylose
alpha 1,4 glycosidic, nonbranching
what bonds make up amylopectin
1, 4 and 1, 6 (branching)
what enzyme hydrolyzes starches
amylase
amylase acts on what type of glycosidic bonds
alpha
glycogen has a similar structure to amylose or amylopectin
amylopectin
what type of glycosidic bonds make up cellulose
beta 1,4
why can’t cellulose be digested by animals
the bonds are beta, alpha amylase that animals (humans) have only breaks alpha bonds
what nutritional component is cellulose a major part of
fiber
what are 2 main functions of dietary fiber
decrease absorption of glucose and cholesterol from intestines
increase bulk of feces
what are the 2 primary sites of dietary carbohydrate digestion
mouth
lumen of intestine
what are the final products of carbohydrate digestion
glucose
galactose
fructose
what are the 2 isoenzymes of alpha amylase
salivary and pancreatic
why does alpha salivary amylase stop functioning in the stomach
due to acidic nature of the stomach
where are the enzymes located that break down the disaccharides of carbohydrate digestion
brush border in intestines
is insulin required with absorption of glucose
no
what type of transport is involved with absorption of carbohydrates (glucose)
secondary active transport
how does secondary active transport work in transport of glucose (carbohydrates)
Na+/glucose symport into cell
Na+ enters blood through Na+/K+ pump
glucose enters blood through GluT2 glucose uniporter (facilitative diffusion- through channel) on basal surface of intestinal cell
D-glucose and D-galactose are absorbed by ___ using ___
secondary active transport
SGLT (sodium-glucose/galactose co-transporter)
where is the SGLT transporter located
intestines
proximal convoluted tubule
the sodium ion dependent transport of glucose and galactose co-transports how many sodium ions for each glucose/galactose
2
the pumping of fructose into the cell uses what transport system
facilitative
what transporter is used with transport of fructose
GLUT5
where is GLUT2 located
liver, intestine, and pancreatic cells
where is GLUT4 located
muscle and fat cells
where is GLUT5 located
small intestine
what GLUT transporter is insulin reactive
4
dietary oligosaccharides enter the ___ and are fermented to form __
large intestines
gas
what can cause dissacharide degradation
intestinal diseases
malnutrition
drugs that injure mucosa of small intestines
what causes acquired enzyme deficiency
loss of brush border enzymes
what type of enzyme is lactase
brush border
what is primary lactose intolerance due to
genetically regulated reduction of lactase production
what is secondary (acquired) lactase intolerance due to
inflammation or infection
what are 2 cases that can cause secondary (acquired) lactose intolerance
celiac disease
giardiasis
what action is prevented by lactase deficiency
lactose–>glucose+galactose
without lactase, where is lactose transported from and to
from small intestine to large intestine
what is produced by lactose breakdown by bacteria in the large intestine without lactase
gas
what can be measured in the breath to determine lactase deficiency
H2
as a result of gas produced due to lactose breakdown by bacteria in the large intestine, what 4 symptoms may a patient experience
bloating
osmotic diarrhea
dehydration
flatulence (gas)
what is the main molecule in carbohydrate metabolism
glucose
why can glucose produce fructose and galactose
they are all epimers
what is metabolism
catabolic+anabolic pathways
proteins, carbohydrates, and fats are all broken down to give off the common product of ___
acetyl CoA
in glycolysis, 1 molecule of glucose produces __ molecules of pyruvate and __ ATP
2
2
what is the importance of glycolytic pathways
provides energy and intermediates for other metabolic pathways
what 2 cells require glycolysis for ATP production
brain cells
RBC
why do RBC need glycolysis to make ATP
they lack a mitochondria
where does glycolysis take place
cytosol
is glycolysis aerobic, anaerobic, or both
both
the ability of glycolysis to provide ATP in the absense of oxygen is especially important in ___ muscle because it allows the muscle to perform at high levels when oxygen supply is insufficient
skeletal
in low oxygen condition, pyruvate produced by glycolysis goes on to produce what
lactate
in normal oxygen condition, pyruvate produced by glycolysis goes on to what pathway
TCA
what are the 2 glucose transporters
Na+ dependent (SGLT)
Na+ independent (GLUT)
why is the first part of glycolysis called the investment phase
it uses ATP
glycolysis produces how many NADH per glucose molecule
2
what occurs during hexokinase reaction in glycolysis
irreversible phosphorylation of glucose, trapping glucose
is there conservation of free energy in the hexokinase reaction of glycolysis
yes
what is a requirement with the hexokinase reaction of glycolysis
Mg2+
does hexokinase have a high or low Km
low
why does hexokinase have a low Km
it has a high affinity for glucose at baseline
is hexokinase or glucokinase used during a fed state
glucokinase
is glucokinase or hexokinase used during a fasting state
hexokinase
is glucokinase or hexokinase used by the liver cells and beta cells of pancreas
glucokinase
is hexokinase or glucokinase used by RBC
hexokinase
why is glucokinase used instead of hexokinase during a fed state
there is a high glucose level that needs to be flooded away
what is the function of glucokinase in beta cells of the pancreas
acts as a glucose sensor determining threshold for insulin secretion
what is the function of glucokinase in liver cells
facilitate glucose phosphorylation during hyperglycemia
does glucokinase function when glucose levels are high or low
high
glucokinase functions especially after what type of macromolecule rich meal
carbohydrate
does glucokinase have a high or low Vmax
why
high
removal of flood of glucose post meal
what is the effect of glucokinase on hyperglycemia
minimizes hyperglycemia during absorptive period
what does a decrease in the activity of glucokinase lead to
maturity onset diabetes of the young type 2 (MODY2)
what inhibits hexokinase
glucose-6-phosphate
does glucokinase undergo feedback inhibition
no
what allows hexokinase to work at baseline glucose levels
low Km (high affinity)
is glucokinase or hexokinase induced by insulin
glucokinase
what does phosphofructokinase-1 of glycolysis catalyze
ATP dependent phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate
what is the regulatory enzyme of glycolysis
phosphofructokinase-1
what are 2 inhibitors of PFK-1 in glycolysis
ATP
citrate
what are 3 activators of PFK-1 in glycolysis
fructose 2,6-bisphosphate
ADP/AMP (low ATP= low energy)
glycolysis produces how many ATP per glucose molecule
4
what 2 enzyme steps of glycolysis produce ATP by substrate level phosphorylation
phosphoglycerate kinase
pyruvate kinase
(*both kinases)
what enzyme step of glycolysis produces NADH
glyceraldehyde 3-phosphate dehydrogenase
how does arsenic poisoning work in relation to glycolysis
it inhibits glyceraldehyde 3-phosphate dehydrogenase by competing with Pi as a substrate
what are 2 inhibitors of glyceraldehyde 3-phosphate dehydrogenase
aresenic
iodoacetate
how does 1,3-bisphosphoglycerate of glycolysis generate ATP
substrate level phosphorylation
what enzyme of glycolysis is inhibited by fluoride
enolase
why is enolase inhibition by fluoride important in labs for blood glucose level checks
fluoride is added to blood to prevent glycolysis in order to receive an accurate blood glucose concentration
what 3 enzymes of glycolysis serve as control sites (regulation)
hexokinase
phosphofructokinase
pyruvate kinase
what molecule must be recognized for glycolysis to proceed
NAD+
in anaerobic respiration, pyruvate turns into what
lactate
in aerobic conditions, pyruvate turns into what
acetyl CoA
what respiration, anaerobic or aerobic, is required for oxidative phosphorylation
aerobic
in anaerobic respiration, pyruvate converts to lactate in order to make __ to continue glycolysis
NAD+
the formation of lactate is always occurring in what main blood cells. why
RBC
no mitohcondria
intense exercise of skeletal muscles results in elevated ___, favoring reduction of pyruvate to lactose
NADH:NAD+ ratio
NADH keeps building up= pyruvate to lactate
what enzyme converts pyruvate to lactate
lactate dehydrogenase
buildup of NADH encourages conversion of __ to __
pyruvate to lactate
what does buildup of lactate in muscle cause
muscle cramps
the extra lactate formed during intense exercise is converted to glucose by __ in the liver
gluconeogenesis
pyruvate to lactate requires __
NADH
lactate to pyruvate requires __
NAD+
when do we call glycolysis aerobic
when oxygen is required to oxidize NADH
when do we call glycolysis anaerobic
conversion of glucose to lactate
what muscle always oxidizes lactate to CO2 and H2O via TCA cycle
heart
what process is required to release energy from glycolysis
TCA cycle
in anaerobic glycolysis, there is a net production of __ ATP and __ NADH
2
0 (NADH is used to replenish NAD+)
in aerobic glycolysis, there is a net production of __ ATP and __ NADH
2
2
each NADH produces __ ATP
2.5/3
in RBC glycolysis, what step can be bypassed
substrate level phosphorylation ATP production step (phosphoglycerate kinase)
what stimulates the bypass of phosphoglycerate kinase in RBC
hypoxia
what is formed as a result of hypoxia in RBC in regards to glycolysis
2,3- BPG
in the presence of 2,3-BPG, oxyhemoglobin unloads __ (more or less) oxygen to tissues
more
what is 2,3-BPG formation called in RBC
BPG shunt
the BPG shunt occurs in what
RBC
transfused blood has a higher or lower 2,3-BPG level
lower
what is the effect of lower 2,3-BPG in transfused blood
less efficient at delivering oxygen to tissue
what is the primary anabolic hormone (fed state)
insulin
what is the primary catabolic hormone (fasting state)
glucagon
insulin and glucagon hormone regulation are involved in what 3 enzymes of glycolysis
glucokinase/hexokinase
phosphofructokinase
pyruvate kinase
what is hemolysis
high lysis of RBC
what enzyme of glycolysis deficiency can lead to hemolytic anemia
pyruvate kinase deficiency
what are 2 reasons RBC require ATP
to maintain biconcave, flexible shape of the cell
(if no ATP= RBC get trapped in narrow capillaries, leads to lysis)
to maintain Na+/K ATPase function (loss of function leads to osmotic fragility= RBC lysis)
how is NADH (reducing equivalent) at NADH step of glycolysis transferred to mitochondria from cytosol
glycerophosphate shuttle and malate shuttle
what is the result of the glycerophosphate shuttle in regards to ATP production
since glycerol-3-phosphate dehydrogenase of the mitochondria is linked to a flavoprotein instead of NAD as it is in the cytosol, 1.5 mole of ATP are formed per atom instead of 2.5
*NADH–>NAD+ gives 2.5/3 ATP
FAD+–>FADH2 gives 1.5/2 ATP
the glycerophosphate shuttle is present in __ but absent in __
brain
heart
is the phosphoglycerate or malate shuttle more universal
malate
what enzyme is used in the glycerophosphate shuttle
glycerol-3-phosphate dehydrogenase
the glycerophosphate shuttle is linked with what molecule
FAD
TCA cycle takes place in ___
mitochondria
what is the final common pathway for the oxidation of fuel molecules
TCA cycle
carbohydrates, protein, and lipids become __ to enter the __ cycle
acetyl CoA
TCA
what enzyme links glycolysis to TCA cycle
pyruvate dehydrogenase
pyruvate is transported into the mitochondria by a ___
protein symporter
pyruvate goes through __ to become acetyl CoA
oxidative decarboxylation
pyruvate is converted to acetyl CoA by what complex
pyruvate dehydrogenase complex
pyruvate dehydrogenase complex is found where
mitochondria
what are the 2 regulatory enzymes of the pyruvate dehydrogenase complex
pyruvate dehydrogenase kinase
pyruvate dehydrogenase phosphatase
in pyruvate dehydrogenase complex, e- is transferred from FAD to NAD+. why
e- transfer potential of FAD is increased by its association with the enzyme
what 3 molecules inhibit pyruvate dehydrogenase complex
acetyl CoA
NADH
ATP
if an enzyme is under the effect on glucagon, it is active in phosphorylated or dephosphorylated state
phosphorylated (kinase enzymes)
if an enzyme is under the effect on insulin, it is active in phosphorylated or dephosphorylated state
dephosphorylated (phosphatase enzymes)
what are the 5 coenzymes of pyruvate dehydrogenase complex
thymine, lipoic acid, CoA, FAD, NAD
what is the affect of calcium on the pyruvate dehydrogenase complex
calcium released during muscle contraction leads to dephosphorylation and activation of pyruvate dehydrogenase complex
what can cause lactic acidosis
pyruvate dehydrogenase complex deficiency
what is the treatment of pyruvate dehydrogenase complex deficiency
no treatment, remove carbohydrates from diet, supplementation with thiamine
(pyruvate dehydrogenase complex coenzyme)
what causes Leigh syndrome
mitochondrial ATP enzyme defects
(defect in enzyme of oxidative phosphorylation, mutation in genes that code for pyruvate dehydrogenase complex, or ATP synthase)
how many carbons enter the TCA cycle as acetyl CoA
2
acetyl CoA entering TCA cycle are balanced by 2 __ exiting
CO2
how many carbons does acetyl CoA have
2
in the TCA cycle the first step is acetyl CoA—>citrate. this is catalyzed by
citrate synthase
the first product of the TCA cycle, citrate, is inhibited by what
citrate
what are the 3 fates of citrate
go into TCA cycle
go to cytosol and activate acetyl CoA carboxylase for FA synthesis
inhibit phosphofructokinase-1 of glycolysis
where is the site of the TCA cycle
mitochondria matrix
citrate is isomerized to isocitrate by what enzyme
aconitase
is aconitase an Fe-S proteins
yes
isocitrate dehydrogenase releases what 2 products
CO2 and NADH
what are the 2 rate limiting steps of the TCA cycle
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
isocitrate dehydrogenase is activated by
ADP
Ca2+
isocitrate dehydrogenase is inhibited by __ and ___
ATP
NADH
what 2 enzymes of TCA release CO2
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
what is an energy rich compound produced during TCA cycle
succinyl CoA
the cleavage of thioester bond of succinyl CoA is coupled to phosphorylation of what
GDP
what are the 2 major concepts of succinyl CoA synthetase (succinate thiokinase)
substrate level phosphorylation
GDP–>GTP
what is the substrate level phosphorylation enzyme of TCA cycle
succinyl CoA synthetase (succinate thiokinase)
what is the only enzyme of the TCA cycle that is embedded in the inner mitochondrial membrane
succinate dehydrogenase (complex II)
what enzyme of the TCA cycle is an FAD containing enzyme
succinate dehydrogenase
what is the enzyme that allows the link between the TCA cycle and ATP formation
succinate dehydrogenase
if you see FMN or FAD, what is involved
riboflavin
FMN is a component of what ETC complex while FAD is a component of what ETC complex
FMN- complex I
FAD- complex II
malate dehydrogenase releases what
NADH
how many ATP are produced from one turn of TCA cycle
10/12
(3 NADH, 1 FADH2, 1 GTP)
what does it mean to say the TCA cycle is amphibolic
intermediates can come in and out
(it is both an oxidative and synthetic process)
what does it mean to say a reaction is anaplerotic in the TCA cycle
generate intermediates
can acetyl CoA convert back to glucose
no
the coenzyme thiamine pyrophosphate of the TCA cycle is derived from what
B1/thiamine
the coenzymes lipoic acid and CoA of the TCA cycle are derived from what
B5/pantotheic acid
the coenzyme flavin adenine dinucleotide (FAD) of the TCA cycle is derived from what
B2/riboflavin
the coenzyme nicotinamide adenine dinucleotide (NAD+) of the TCA cycle is derived from what
B3/niacin
the complete split of glucose by aerobic respiration produces how many ATP
38 (or 32)
the complete split of glucose by anaerobic respiration produces how many ATP
2
why can’t acetyl CoA form glucose
acetyl CoA is released as CO2 through oxidative decarboxylation reaction
what is beriberi
thiamine deficiency leads to low transketolase activity of RBC
arsenic poisoning is due mostly to inhibition of enzymes that require __
lipoic acid (pyruvate dehydrogenase complex and TCA)
arsenic affects what 3 spots of the TCA cycle
fluoroacetate
arsenate
malonate
what is this only source of fuel for skeletal muscle under anaerobic conditions
glucose
what does gluconeogenesis help clear
lactate and glycerol
what is the first source of blood glucose in a fasting state
liver glycogen
what is gluconeogenesis
making glucose from non-carbohydrate sources
what are the 5 substrates for gluconeogenesis
lactate
pyruvate
glucogenic AA
propionate
glycerol
where is the location of gluconeogenesis
cytosol
during an overnight fast, which organs does gluconeogenesis occur in
liver (mostly, 90%)
kidney (10%)
during a prolonged fast, which organ is the main organ of gluconeogenesis
kidney
the 3 reversible steps of glycolysis are catalyzed by what 3 enzymes
hexokinase
phosphofructokinase
pyruvate kinase
what is required as a cofactor with pyruvate carboxylase in gluconeogenesis
biotin
where is pyruvate carboxylase of gluconeogenesis located
mitochondria
what activates pyruvate carboxylase
acetyl CoA
what is the rate limiting steps of gluconeogenesis
pyruvate carboxylase
phosphoenolpyruvate carboxykinase
fructose 1, 6-bisphosphatase
glucose 6-phosphate
if there is a carboxylase enzyme, what cofactor is always involved
biotin
what is a source of biotin deficiency
raw egg whites
*contains avidin which binds biotin and prevents it’s absorption
in what state is pyruvate carboxylase activated by acetyl CoA
fasting
where is oxaloacetate of gluconeogenesis located
mitochondrial matrix
how does oxaloacetate, which is synthesized in the mitochondrial matrix, reach the cytosol to be converted to phosphoenolpyruvate
oxaloacetate is converted to malate through malate dehydrogenase
malate reaches the cytosol
malate is converted back to oxaloacetate by malate dehydrogenase
what are the 2 regulatory enzymes of gluconeogenesis
pyruvate carboxylase
fructose 1,6-bisphosphate
what enzyme converts glucose 6-phosphate to glucose in gluconeogenesis
glucose 6-phosphatase
in what organs is glucose 6-phosphatase, needed to convert glucose 6-phosphate to glucose, mostly located
liver
kidneys
in what organelle is glucose 6-phosphatase, needed to convert glucose 6-phosphate to glucose, located
endoplasmic reticulum
where in the body is glucose 6-phosphatase, an enzyme of gluconeogenesis, absent
muscle
what supplies the ATP required for gluconeogenesis
fatty acid oxidation
