concept 1d part1 Flashcards
(126 cards)
1
Q
glucose entry into a cell
A
into most cells it is driven by concentration
is independent of sodium, unlike absorption from digestive tract
normal concentration in peripheral blood is 5.5 mM (range 4-6)
2
Q
glucose transporters
A
GLUT 1 GLUT 2 GLUT 3 GLUT 4 2 and 4 are the most significant bc they are located in specific cells and are highly regulated
3
Q
GLUT 2
A
low-affinity transporter
in hepatocytes (liver) and pancreatic cells
captures excess glucose from blood after a meal
primarily for storage
when glucose concentration drops below Km for the transporter (~15mM) most glucose leaves the liver and enters circulation
4
Q
GLUT 4
A
in adipose tissue and muscle
responds to the glucose concentration in peripheral blood
stored in cytoplasm and when increased insulin triggers exocytosis and transporters move to the membrane
Km is ~5mM so transporter is saturated when blood glucose is a bit higher than normal
5
Q
type 1 diabetes
A
insulin is absent and cannot stimulate the insulin receptors
blood glucose rises, leading to immediate and long-term symptoms
6
Q
type 2 diabetes
A
receptors become insensitive to insulin and fail to bring GLUT 4 transporters to the cell surface
blood glucose rises, leading to immediate and long-term symptoms
7
Q
diabetes symptoms
A
immediate- increased urination, increased thirst, ketoacidosis
long term- blindness, heart attacks, strokes, nerve damage
8
Q
glycolysis
A
cytoplasmic pathway that converts glucose into 2 pyruvate
releasing energy captured in 2 substrate-level phosphorylations and 1 oxidation reaction
occurs under both aerobic and anaerobic conditions
energy carrier is NADH
9
Q
5 enzymes of glycolysis
A
hexokinase and glucokinase phophofructokinases (PFK-1 and PFK-2) glyceraldehyde-3-phosphate dehydrogenase 3-phosphoglycerate kinase pyruvate kinase
10
Q
hexokinase
A
converts glucose to glucose-6-phosphate in the first step of glycolysis, molecule is then trapped inside the cell
present in most tissues
low Km, reaches maximum velocity of low glucose concentration
inhibited by glucose 6-phosphate
11
Q
glucokinase
A
converts glucose to glucose-6-phosphate in the first step of glycolysis, molecule is then trapped inside the cell
found only in the liver and pancreatic beta-islet cells
high Km, acts on glucose proportionally to its concentration
in the liver it is induced by insulin
12
Q
phosphofructokinases-1 (PFK-1)
A
rate-limiting enzyme and main control point in glycolysis
fructose 6-phosphate is phosphorylated to fructose 1,6-biphosphate using ATP
inhibited by ATP and citrate
activated by AMP
in hepatocytes insulin stimulates and glucagon inhibits by indirect mechanism w/ PFK-2
13
Q
phosphofructokinases-2 (PFK-2)
A
converts a tiny amount of fructose 6-P to fructose 2,6-biphosphate (F2,6-BP)
F2,6-BP activates PFK-1
activated by insulin and inhibited by glucagon
found mostly in the liver
14
Q
glyceraldehyde-3-phosphate dehydrogenase
A
catalyzes an oxidation and addition of inorganic phosphate (Pi) to glyceraldehyde 3-P
results in high-energy intermediate 1,3-biphosphateglycerate
also reduction of NAD+ to NADH
15
Q
3-phosphoglycerate kinase
A
transfers high-energy phosphate from 1,3-biphosphoglycerate to ADP
forms ATP and 3-phosphoglycerate, an example of substrate-level phosphorylation
16
Q
substrate-level phosphorylation
A
ADP is directly phosphorylated to ATP using a high-energy intermediate
not dependent on oxygen, unlike oxidative phosphorylation
only means of ATP generation in anaerobic tissues
17
Q
pyruvate kinase
A
catalyzes a substrate-level phosphorylation of ADP using high-energy substrate phosphoenolpyruvate (PEP)
activated by fructose 1,6-biphosphate from PFK-1 reaction
this is a feed-forward activation
18
Q
feed-forward activation
A
meaning that the product of an earlier reaction stimulates, or prepares, a later reaction
19
Q
fermentation
A
conversion of pyruvate to either ethanol and carbon dioxide (yeast) or lactic acid (animal cells)
happens in the absence of oxygen
result is replenishing NAD+
20
Q
animal fermentation
A
pyruvate to lactic acid
key enzyme is lactate dehydrogenase
oxidizes NADH to NAD+, replenishing the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
21
Q
yeast cell fermentation
A
pyruvate (3C) to ethanol (2C) and carbon dioxide (1C)
results in replenishing of NAD+
22
Q
intermediates of glycolysis
A
dihydroxyacetone phosphate (DHAP)
1,3-biphosphoglycerate (1,3-BPG)
phosphoenolpyruvate (PEP)
23
Q
dihydroxyacetone phosphate (DHAP)
A
used in hepatic and adipose tissues
triacylglycerol synthesis
formed from fructose 1,6-bisphosphate
isomerized to glycerol-3-phosphate, then converted to glycerol which is the backbone of triacylglycerols
24
Q
1,3-bisphosphate
A
high-energy intermediate
used to generate ATP by substrate-level phosphorylation, only ATP gained in anaerobic respiration
25
phosphoenolpyruvate
high-energy intermediate
| used to generate ATP by substrate-level phosphorylation, only ATP gained in anaerobic respiration
26
irreversible enzymes
Hexokinase
Glucokinase
PFK-1
Pyruvate Kinase
How Glycolysis Pushes Forward the Process: Kinase (mnemonic)
27
glycolysis in erythrocytes
anaerobic glycolysis
only pathway for ATP production, 2 ATP per glucose
bisphosphoglycerate mutase produces 2,3-bisphosphogylcerate (2,3-BPG) from 1,3-BPG in glycolysis
2,3-BPG binds allosterically to beta-chain of hemoglobin A and decreases its affinity for oxygen in tissues
28
other monosaccahrides used by cells
galactose and fructose can contribute to ATP production by feeding into glycolysis or other metabolic processes
29
galactose
monosaccharide found in dairy, from disaccharide lactose
30
lactose
disaccharide found in milk
| hydrolyzed to galactose and glucose by lactase in the duodenum
31
galactose metabolism
transported to the liver though the hepatic portal vein and transported to other tissues
then phosphorylated by galactokinase, trapping it in the cell, resulting in galactose 1-phosphate
that is then converted to glucose 1-phosphate by galactose-1-phosphate uridyltransferase and epimerase, which eventually results in glucose
*important enzymes: galactokinase and galactose-1-phosphate uridyltransferase
32
epimerase
enzymes that catalyze the conversion of one sugar epimer to another
33
primary lactose intolerance
caused by hereditary deficiency of lactase
| lactose cannot be broken down
34
secondary lactose intolerance
precipitated at any age by gastrointestinal disturbances that cause damage to the intestinal lining where lactase is found
35
fructose
monosaccharide found in fruit and honey
| sucrose is hydrolyzed by sucrase to form fructose and glucose
36
fructose metabolism
fructose is absorbed into the hepatic portal vein
liver phosphorylates fructose using fructokinase, trapping it in cell
results in fructose 1-phosphate, which is then cleaved into glyceraldehyde and DHAP by aldolase B
then forms glyceraldehyde 3-P used in glycolysis, glycogenesis, and gluconeogenesis
37
pyruvate dehydrogenase complex (PDH)
irreversible reaction
converts pyruvate to acetyl CoA for citric acid cycle
in the mitochondria
38
pyruvate dehydrogenase
in the liver activated by insulin
in the nervous system it is not responsive to hormones
converts pyruvate to acetyl CoA in the mitochondria
large complex of enzymes carrying out multiple reactions in succession, requires cofactors and coenzymes
inhibited by acetyl-CoA
39
glycogen
branced polymer of glucose
storage form of glucose
synthesis and degradation in the liver and skeletal muscle
stored in the cytoplasm as granules
40
glycogen granules
have central protein core with polyglucose chains radiating outward to form a sphere
composed entirely of linear chains w/ high density glucose near the core
41
liver glycogen
is broken down to maintain a constant level of glucose in the blood
42
muscle glycogen
is broken down to provide glucose to the muscle during vigorous exercise
43
glycogenesis
synthesis of glycogen granules
begins with core protein glycogenin
glucose addition to a granule begins with glucose 6-phosphate, converted to glucose 1-phosphate
activate by uridine diphosphate
permits integration into glycogen chain by glycogen synthase
44
glycogen synthase
rate-limiting enzyme of glycogen synthesis
forms alpha-1,4 glycosidic bonds found in linear glucose chains of granule
stimulated by glucose 6-phosphate and insulin
inhibited by epinephrine and glucagon
45
branching enzymes
responsible for introducing alpha-1,6-linked branches into granule
hydrolyzes one of the alpha-1,4 bonds to release block of oligoglucose, which is then moved and added to different location
this forms an alpha-1,6 bond to create branch
46
glycogenolysis
process of breaking down glycogen
rate-limiting enzyme is glycogen phosphorylate
glucose 1-phosphate formed by glycogen phosphorylate is converted to glucose 6-phosphate using same mutate as glycogen synthesis
47
glycogen phosphorylase
breaks alpha-1,4 bonds
releasing glucose 1-phosphate from periphery of granule
can't break branches
activated by glucagon in liver and AMP and epinephrine in skeletal muscles
48
debranching enzymes
2 enzyme complex that deconstructs the branches in glycogen that have been exposed by glycogen phosphorylase
breaks alpha-1,4 bond adjacent to branch point and moves small oligoglucose chain that is release to exposed end of chain
forms a new alpha-1,4 bond
hydrolyzes the alpha-1,6 bond releasing the single residue at branch point as free glucose
49
gluconeogenesis
production of glucose from other biomolecules
carried out by liver and kidneys
helps maintain glucose levels during fasting
promoted by glucagon and epinephrine
inhibited by insulin
50
important substrates for gluconeogenesis
glycerol 3-phosphate: from stored fats, or triacylglycerols, in adipose tissue
lactate: from anaerobic glycolysis
glucogenic amino acids: from muscle proteins
51
glucogenic amino acids
can be converted into intermediates that feed into gluconeogenesis
all except leucine and lysine
52
ketogenic amino acids
can be converted into ketone bodies
| which can be used as alternative fuel, particularly during prolonged starvation
53
important enzymes of gluconeogenesis
pyruvate carboxylase
phosphoenolpyruvate carboxykinase (PEPCK)
fructose-1,6-bisphosphatase
glucose-6-phophatase
54
pyruvate carboxylase
mitchondrial enzyme
activated by acetyl-CoA
produces oxaloacetate as citric acid cycle intermediate
OAA is reduced to malate which is transported to cytoplasm and oxidized to OAA
55
phosphoenolypyruvate carboxykinase (PEPCK)
in cytoplasm
induced by glucagon and cortisol
converts OAA to phosphoenolpyruvate (PEP) in reaction with GTP
PEP continues in pathway to 1,6-bisphosphate
56
fructose-1,6-bisphosphate
in cytoplasm
rate-limiting enzyme and control point of gluconeogenesis
hydrolyzing fructose 1,6-bisphosphate to produce fructose 6-phosphate
activated by ATP
inhibited by AMP and fructose 2,6-bisphosphate
57
glucose-6-phosphatase
found in lumen of endoplasmic reticulum in liver cells
glucose 6-phosphate transported to ER and converted into glucose
which can diffuse out of cell
absence of enzyme in skeletal muscle means that glycogen cannot serve as a source of blood glucose and use only within the muscle
58
pentose phosphate pathway (PPP)
aka hexose monophosphate (HMP) shunt
occurs in cytoplasm of all cells
2 major functions: production of NADPH and a source of ribose 5-phosphate for nucleotide synthesis
59
first part of PPP
glucose 6-phosphate is eventually converted to ribulose 5-phosphate
irreversible pathway
produces NADPH
rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD)
60
glucose-6-phosphate dehydrogenase (G6PD)
rate-limiting enzyme of pentose phosphate pathway
induced by insulin and NADP+
inhibited by its product, NADPH
61
second part of PPP
begins with ribulose 5-phosphate
series of reversible reactions
produce equilibrated pool of sugars for biosynthesis, including ribose 5-phosphate, fructose 6-P, and glyceraldehyde 3-P
accomplished by transketolase and transaldolase
62
NADH
produced from the reduction of NAD+ and can then feed into the electron transport chain to indirectly produce ATP
63
NADPH
primarily acts as an electron donor in biochemical reactions
thought of as a potent reducing agent bc it helps other molecules be reduced
64
why do cells require NADPH?
biosynthesis, mainly of fatty acids and cholesterol
assisting in cellular bleach production in certain white blood cells, thereby contributing to bactericidal activity
maintenance of a supply of reduced glutathione to protect against reactive oxygen species (acting as the body's natural antioxidant)
protecting cells from free radical oxidative damage caused by peroxides
65
glutathione
reducing agent that can help reverse radial formation before damage is done to the cell
66
rate limiting enzymes for carbohydrate metabolism
glycolysis: phophofructokinase-1
fermentation: lactate dehydrogenase
glycogenesis: glycogen synthase
glycogenolysis: glycogen phosphorylase
glyconeogenesis: fructose-1,6-bisphosphatase
pentose phosphate pathway: glucose-6-phosphate dehydrogenase
67
citric acid cycle
aka Krebs cycle
in mitochondria
function is the oxidation of acetyl-CoA to CO2 and H2O
produces high-energy electron-carrying molecules NADH and FADH2
68
formation of acetyl-CoA
pyruvate is converted into a a 2 carbon acetyl group and carbon dioxide
this is catalyzed by the multi enzyme complex pyruvate dehydrogenase complex located in the mitochondrial matrix
reaction is exergonic
69
coenzyme A (CoA)
written as CoA-SH in reaction
is a thiol containing an SH group
when reacted with pyruvate it forms acetyl-CoA which is a thioester
70
thioester
contains a sulfer instead of a typical oxygen ester -OR
| has high-energy properties, when it undergoes a reaction such as hydrolysis a significant amount of energy is released
71
enzymes of the pyruvate dehydrogenase complex
```
pyruvate dehydrogenase (PDH)
dihydropropyl transacetylase
dihydrolipoyl dehydrogenase
pyruvate dehydrogenase kinase
pyruvate dehydrogenase phosphatase
*the first 3 work to convert pyruvate to acetyl CoA and the last 2 regulate the actions of PDH
```
72
pyruvate dehydrogenase (PDH)
oxidizes pyruvate yielding CO2
remaining 2 carbon binds covalently to thiamine pyrophosphate (TPP), coenzyme held by non covalent interactions to PDH
Mg2+ is also needed
73
dihydropropyl transacetylase
2 carbon molecule bound to TPP is oxidized
then transferred to lipoic acid, coenzyme covalently bound to the enzyme
lipoid acid's disulfide group acts as oxidizing agent producing acetyl group, bound via thioester bond
enzyme catalyzes CoA-SH causing transfer of acetyl group forming acetyl-CoA
74
dihydrolipoyl dehydrogenase
FAD is coenzyme used to deoxidize lipoic acid
this allows it to facilitate acetyl-CoA formation in future reactions
FAD is reduced to FADH2
75
other pathways to form acetyl-CoA
fatty acid oxidation (beta oxidation)
amino acid catabolism
ketones
alcohol
76
fatty acid oxidation
activation occurs to form thirster bond b/w carboxyl group of fatty acids and CoA forming fatty acyl-CoA in the intermembrane of mitochondria
this molecule cannot cross the membrane so FA is transported to carnation via transesterification so it can cross the inner membrane
once accros FA is transported back to mitochondrial CoA-SH
then beta oxidation occurs to remove 2 carbon fragment of carboxyl end resulting in acetyl-CoA
77
amino acid catabolism
amino acids lose their amino group via transamination
their carbon skeletons form ketone bodies, termed ketogenic for this reason
then ketones are used to produce acetyl-CoA
78
ketones
reverse reaction as when PDH is inhibited and acetyl-CoA forms ketones
79
alcohols
alcohols are converted using alcohol dehydrogenase and acetaldehyde dehydrogenase
accompanied by NADH buildup which inhibits Krebs cycle
acetyl-CoA formed in this process used primarily to synthesize fatty acids
80
key reactions of the citric acid cycle
1. citrate formation
2. citrate isomerized to isocitrate
3. alpha-ketoglutarate and CO2 formation
4. succinyl-CoA and CO2 formation
5. succinate formation
6. fumarate formation
7. malate formation
8. oxaloacetate formed anew
81
citrate formation
acetyl-CoA and oxaloacetate undergo condensation
forming citryl-CoA as intermediate
hydrolysis yields citrate and CoA-SH
this is catalyzed by citrate synthase
second step favors formation of citrate and pushes rxn in forward direction
82
citrate isomerized to isocitrate
achiral citrate is isomerized to 1 of 4 possible isomers of isocitrate
1. citrate binds at 3 points to aconitase
2. water is lost from citrate, yielding cis-aconitate
3. water is readded to form isocitrate
rxn results in switching of a hydrogen for a hydroxyl group, necessary to facilitate subsequent oxidative decarboxylation
83
alpha-ketoglutarate and CO2 formation
isocitrate oxidized to oxalosuccinate by isocitrate dehydrogenase
oxalosuccinate is decarboxylated to form alpha-ketoglutarate and CO2
the first carbon from acetyl-CoA is lost here
first NADH produced
*isocitrate dehydrogenase is the rate-limiting enzyme of citric acid cycle
84
succinyl-CoA and CO2 formation
carried out by alpha-ketoglutarate dehydrogenase complex (similar to PDH complex)
alpha-ketoglutarate and CoA come together and produce succinyl-CoA and CO2
CO2 represents second and last carbon lost from acetyl-CoA
another NADH is produced
85
succinate formation
hydrolysis of thioester in succinyl-CoA yields succinate and CoA-SH
catalyzed by succinyl-CoA synthetase
coupled with phosphorylation of GDP to GTP driven by energy from thioester hydrolysis, then catalyzed by nucleosidediphosphate kinase to transfer phosphate from GTP to ADP producing ATP
86
dehydrogenase
substype of oxidoreductases, enzyme that catalyze a redox reaction
transfer hydride ion (H-) to an electron acceptor, usually NADH or FADH2
*when you see this look for high-energy electron carrier being formed
87
synthetases
enzyme create new covalent bonds with energy input
| unlike syntheses that don't require energy input to create new covalent bonds
88
fumarate formation
*only step that doesn't take place in the mitochondrial matrix, it occurs in the inner membrane
succinate undergoes oxidation to fumarate
catalyzed by succinate dehydrogenase
FAD is reduced to FADH2
89
succinate dehydrogenase
considered a flavoprotein
covalently bonded to FAD, the electron acceptor in fumarate formation reaction
an integral protein of the inner mitochondrial membrane, reason fumarate formation takes place there
90
malate formation
hydrolysis of the alkene bond in fumarate forming malate
catalyzed by fumarase
only L-malate forms in this reaction
91
oxaloacetate formed anew
oxidation of malate to oxaloacetate
catalyzed by malate dehydrogenase
third NAD+ is reduced to NADH
newly formed oxaloacetate ready to begin another citric acid cycle
92
substrates of the citric acid cycle
```
Pyruvate
Citrate
Isocitrate
alpha-Ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Oxaloacetate
```
Please, Can I Keep Selling Seashells For Money, Officer? (mnemonic)
93
glycolysis energy yield
```
2 ATP
2 NADH (2.5 ATP per NADH=5ATP)
```
94
PDH complex energy yield
1 NADH (2.5 ATP)
95
citric acid cycle energy yield
```
3 NADH (7.5 ATP)
FADH2 (1.5 ATP per FADH2=1.5 ATP)
GTP (=1 ATP)
```
96
PDH complex regulation
by phosphorylation of PDH, facilitated by pyruvate dehydrogenase kinase
when ATP levels rise, phosphorylating ADH inhibits acetyl-CoA production
complex is reactivated by pyruvate dehydrogenase phosphatase in response to high levels of ADP, reactivating acetyl-CoA production
97
control points of citric acid cycle
```
citrate synthase (1)
isocitrate dehydrogenase (3)
alpha-Ketogluterate dehydrogenase complex (4)
```
98
citrate synthase regulation
ATP and NADH are allosteric inhibitors of citrate synthase
| also inhibited by citrate and succinyl-CoA
99
isocitrate dehydrogenase regulation
rate-limiting enzyme of citric acid cycle
inhibited by energy products of cycle: ATP and NADH
ADP and NAD+ function as allosteric activators
100
alpha-ketoglutarate dehydrogenase complex regulation
reaction products, succinyl-CoA and NADH are inhibitors
| also inhibited by ATP
101
cristae
folds in the inner mitochondrial membrane
| maximize surface area
102
proton-motive force
proton concentraion gradient across the inner mitochondrial membrane that is created in the electron transport chain and used in oxidative phosphorylation
essential for generating ATP, it is this gradient that produces ATP not the flow of electrons
103
final step of aerobic respiration
occurs in 2 steps: electron transport along the inner mitochondrial membrane and generation of ATP via ADP phosphorylation
these 2 processes are coupled
NADH and FADH2 for earlier transfer electrons to carrier proteins in membrane
electrons given to oxygen to form water
as this is happening energy released from transporting electrons facilitates protons transport at 3 locations
protons moved from mitochondrial matrix to inter membrane space creating greater concentration gradient of hydrogen ions used to drive ATP production
104
reduction potential
how likely molecule is to be reduced
physical property that determines the direction of electron flow in ETC
if pair 2 molecules w/ different reduction potentials, molecule with higher potential will be reduced while other molecule will be oxidized -->ETC is a series of oxidations and reductions that occur via the same mechanism
105
electron transport chain
group of protein complexes on the inner mitochondrial membrane that are responsible for flow of electrons
series of oxidations and reductions
proteins transfer electrons donated by NADH and FADH2 in a specific order and direction in order to yield energy to make ATP
contain 4 proteins complexes
106
ETC proteins complexes
```
Complex I (NADH-CoQ oxidoreductase)
Complex II (succinate-CoQ oxidoreductase)
Complex III (CoAH2-cytochrome c oxidoreductase)
Complex IV (cytochrome c oxidase)
```
107
Complex I
NADH-CoQ oxidoreductase
transfer of electrons from NADH to CoQ
catalyzed from the first complex
over 20 subunits, 2 important: protein including iron-sulfur cluster and flavoprotein that oxidizes NADH
flavoprotein has a coenzyme called flavin mono nucleotide (FMN) covalently bound to it
108
process in Complex I
1. NADH transfers its electron over to FMN, becoming oxidized to NAD+ as FMN is reduced to FMNH2
2. flavoprotein becomes reoxidized while iron-sulfer subunit is reduced
3. reduced iron-sulfur subunit donates electrons it received from FMNH2 to CoQ which becomes CoQH2
this complex pumps 4 protons (H+) into the inter membrane space
net passing of electrons from NADH to CoQ to form NAD+ and CoQH2
109
Complex II
Succinate-CoQ oxidoreductase
receives electrons from succinate, a citric acid cycle intermediate
FAD is covalently bound to complex II
like complex I it transfers electrons to CoQ
succinate dehydrogenase is part of complex
110
process in Complex II
1. succinate is oxidized to fumarate upon interaction with FAD (bound to complex) which is the converted to FADH2
2. FADH2 is reoxidized to FAD as it reduces an iron-sulfate protein
3. iron-sulfate protein is reoxidized and CoQ is reduced to CoQH2
NO protons (H+) pumping occurs, no contribution to the proton gradient
net passing of electrons from succinate to CoQ to from fumarate and CoQH2
111
Complex III
CoQH2-cytochrome c oxidoreductase
facilitates the transfer of electrons from coenzyme Q to cytochrome c
contribution to the proton-motive force via the Q cycle
CoQH2 + 2 cytochrome c [w/ Fe3+]
--> CoQ + 2 cytochrome c [w/ Fe2+] +[2H+]
112
cytochrome
proteins with heme groups
| iron is reduced to Fe2+ and reoxidized to Fe3+
113
Q cycle
1. 2 electrons are shuttled from CoQH2 (ubiquinol) near the inter membrane space to a molecule of CoQ (ubiquinone) near the mitochondrial matrix
2. another 2 electrons attached to heme moieties, reducing 2 molecules of cytochrome c
*this process happens twice since 2 molecules of CoQH2 were produced in the other complexes
4 protons are pumped into the inter membrane space, increasing the gradient
114
Complex IV
cytochrome c oxidase
facilitates transfer of electrons from cytochrome c to oxygen
oxygen is the final electron acceptor
subunits of cytochrome a, cytochrome a3, and Cu3+ ions
cytochrome a and a3 make up cytochrome oxidase
115
process in Complex IV
series of redox reactions
cytochrome oxidase gets oxidized as oxygen becomes reduced and forms water
final location of proton pumping, 2 protons are pumped across the membrane
2 cytochrome c [w/Fe2+] + 2H+ +1/2 O2
--> 2 cytochrome c [w/Fe3+] + H2O
116
electrochemical gradient
a gradient that has both chemical and electrostatic properties
proton-motive force
stores energy
117
formation of proton-motive force
[H+] increases in the inter membrane space during the process of the ETC
as it increase 2 things happen: pH drops in the inter membrane space and the voltage difference b/w the inter membrane space and matrix increases due to proton pumping
this creates and electrochemical gradient
stores energy and ATP synthase harnesses this energy to form ATP
118
NADH shuttle mechanism
transfers the high-energy electrons of NADH to a carrier that can cross the inner mitochondrial membrane
this is bc NADH cannot directly cross
2 mechanisms: glycerol 3-phosphate shuttle and malate-aspartate shuttle
119
glycerol 3-phosphate shuttle
cytosol contains glycerol 3-phosphate dehydrogenase which oxidizes cytosolic NADH to NAD+ and forming glycerol 3-phosphate
another glycerol 3-phosphate dehydrogenase is on the inner mitochondrial membrane that is FAD dependent
FAD is reduced to FADH2 which transfers its electrons to ETC via complex II
generates 1.5 ATP for every cytosolic NADH
120
malate-aspartate shuttle
1. cytosolic oxaloacetate is reduced to malate by malate dehydrogenase also oxidizing NADH to NAD+
2. malate crosses the membrane and is oxidized to form oxaloacetate and NADH in the inter membrane space
3. NADH is passed to ETC via complex 1
4. oxaloacetate is transaminate to aspartate with aspartate transaminase, this crossed back into the cytosol can be reconverted to oxaloacetate to begin the process again
* generates 2.5 ATP for every NADH
121
ATP synthase
protein complex that links the electron transport chain and ATP synthesis
spans the entire inner mitochondrial membrane and protrudes into the matrix
122
Fo (F not/sub0)
```
portion of ATP synthase that spans the membrane
function as an ion channel
protons travel through it along their gradient back into the matrix
```
123
chemiosmotic coupling
utilization of the proton-motive force generated by the electron transport chain to drive ATP synthesis in oxidative phosphorylation
describes a direct relationship b/w proton gradient and ATP synthesis
124
synthesis of ATP
chemiosmotic coupling harnesses the chemical energy of the gradient to phosphorylate ADP to ATP
ETC generates high concentration of protons in the inter membrane space
protons flow through the Fo ion channel to ATP synthase back into the matrix
F1 portion of ATP synthase utilizes the energy from the gradient to phosphorylate ADP to ATP
125
conformational coupling
relationship b/w proton gradient and ATP synthesis is indirect
ATP is released by the synthase as a result of conformational change caused by the gradient
F1 portion is reminiscent of a turbine, spinning within a stationary compartment to facilitate harnessing of energy for chemical bonding
126
regulation of oxidative phosphorylation
O2 and ADP are key regulators
low O2, oxidative phosphorylation is decreased, NADH and FADH2 levels increase, which inhibits the citric acid cycle
--> respiratory control
in presence of adequate O2, regulated by ADP
ADP allosterically activates isocitrate dehydrogenase, increasing citric acid cycle and production of NADH, increasing rate of ETC and oxidative phosphorylation
