Final Flashcards
1
Q
Enzymes regulated by BOTH ATP/ADP
Inhibited by High ATP
A
PFK-1, Pyruvate Kinase, PDComplex, Isocitrate Dehydrogenase
2
Q
Enzymes only INHIBITED by high ADP
A
Pyruvate Carboxylase, PEPCK
ATP has no effect
3
Q
Activation step for Glycogen Synthesis
A
1 UTP + G-1-P –> UDP-Glucose (During Fed State!)
By udp-glucose-pyrophosphatase
4
Q
Activation step for FAS
A
ACC - Adds CO2 + ATP to Acetyl CoA to make Malonyl CoA (Fed State)
5
Q
Activation step for Cholesterol Synthesis
A
(Not rate limiting step)
Making Isoprene Unit = 3 ATP + Mevalonate –> 3-Isopentenyl Pyrophosphate (Fed State)
6
Q
Activation step for Phospholipid synthesis
A
CTP + Polar Head group or DAG (Fed State)
7
Q
Activation step for Triglyceride synthesis
A
Sike! there is none
8
Q
Activation steps for Gluconeogenesis
A
6 ATP/GTP, during various regulation steps - Energy Source = beta-oxidation of FAs (Fasted state)
9
Q
Activation step for FA oxidation (Beta oxidation)
A
Fatty Acid chain + Acyl (not acetyl) CoA + ATP –> FattyAcid-CoA (Driven by pyrophosphate hydrolysis)
10
Q
Processes during fed state
A
Glycolysis, PDC, Glycogen synthesis, FA synthesis, Cholesterol Synthesis
11
Q
Processes during fasted state
A
Ketogenesis, Gluconeogenesis, Glycogen degradation, FA oxidation
12
Q
Rate Limiting step for Cholesterol Synthesis
A
HMG CoA Reductase:
HMG-CoA –> Mevalonate
Requires 2 NADPH
13
Q
Rate Limiting Step for Fatty Acid Synthesis
A
Acetyl CoA Carboxylase:
Acetyl CoA + CO2 + ATP –> Malonyl CoA
14
Q
All Carboxylases require ______ as coenzyme
A
Biotin
15
Q
Rate Limiting step for Glycolysis
A
PFK1
F-6-P –> F-1,6-BP
16
Q
Rate Limiting Step for TCA Cycle
A
Isocitrate Dehydrogenase:
Isocitrate + NAD+ –> alpha-ketoglutarate + CO2
17
Q
Rate Limiting Step for Gluconeogenesis
A
F-1,6-Bisphosphatase
F-1,6-BP –> F-6-P
18
Q
Reactions in mitochondria
A
FA oxidation
PDC (Acetyl CoA Production)
TCA Cycle
Oxidative phosphorylation
Both mito + cytosol:
Gluconeogenesis
19
Q
Reactions in Cytoplasm
A
Glycolysis
FA Synthesis
Cholesterol Synthesis
Both:
GNG
20
Q
Structure of cholesterol
A
three 6 membered, one 5 membered
21
Q
Acetone must be exhaled because ketone body production leads blood pH to ______
A
Decrease – Acidosis
22
Q
TCA Cycle Regulated by
A
[Acetyl CoA] and [OAA], ATP utilization, O2, NAD+/NADH
23
Q
Muscle Contraction effects:
A
TCA cycle increases, O2 consumption increases, ADP increases, H+ gradient decreases (ox. phos. increases to restore H+ Gradient)
24
Q
Insulin receptor cascade
A
NO G Protein
Binds –> IRS-1 phos. –> PI-3-Kinase phos. –> PIP2 phos. to PIP3 –> PDK-1 phos. –> AKT phos
25
GPCR Oxytocin
G protein activated --> Alpha subunit activates PLC --> PIP2 cleaved to IP3 and DAG --> IP3 releases CA2+ --> Ca2+ and DAG activate PKC
26
GPCR Epi/Glucagon
G-alpha activates adenylate cyclase --> cAMP produced --> cAMP activates PKA
27
RTK: RAS/RAF
GRB2 --> Sos --> Ras --> Raf --> Mek --> Erk1/2 --> Other shit
28
Do insulin receptors dimerize?
They don't need to, they are always dimerized
29
Substrate level phosphorylation
Creatine phosphate, 1,3-BPG from step 6 glycolysis, PEP from step 10 glycolysis
30
Hexokinase/Glucokinase
Glucokinase (high Km) = Liver
Hexokinase = brain, all other tissues
Trap Glucose within cell to commit it to glycolysis
31
TCA Cycle intermediates are used in other pathways:
Citrate --> FAs, sterols
Alpha-ketoglutarate --> Glutamate --> Other amino acids --> Purines
Succinyl CoA --> porphyrins/heme
Oxaloacetate --> Aspartate -> Purines/Pyrimidines
OAA --> Glucose via GNG
32
Glucokinase regulation
Not FBI, inducible by insulin
33
Hexokinase regulation
FBI by G-6-P (product)
34
PFK-1 regulation
No hormonal
+: AMP, F-2,6-P (Not product F-1,6-P)
-: Citrate, ATP
35
PFK-2 regulation
Normal hormonal fed state active (NHFedSA)
36
Pyruvate Kinase
High energy charge inhibition (HECI), normal hormonal fed state active (NHFedSA)
37
PDH Complex
Pyruvate + NAD+ + CoA --> Acetyl CoA + CO2 + NADH + H+
38
PDH Complex regulation
High energy charge inhibition (HECI),
+: ADP, NAD+, Pyruvate
-: ATP, NADH, Acetyl CoA
NHFedSA
39
Is there hormonal regulation in the TCA Cycle?
NO! There is no I/G effect on TCA Cycle
40
Isocitrate dehydrogenase regulation
HECI (ATP/ADP),
+: NAD+
-: NADH
41
Alpha-ketoglutarate dehydrogenase regulation
HECI,
+: NAD+
-: NADH, Succinyl CoA
42
Which enzymes reduce NAD+ in TCA cycle?
All the dehydrogenases
43
Glycogen synthase
UDP-Glucose to alpha-1,4 linkages
44
Glycogen synthase regulation
Activated by G-6-P and dephosphorylated+activated by Protein Phosphatase 1,
NHFedSA!
45
NHFSA (Normal hormonal fed state active enzymes)
PFK-2, Pyruvate Kinase, PDH Complex, Glycogen synthase, ACC, HMG-CoA Reductase,
46
Glycogen Phosphorylase regulation
Protein phosphorylase dephosphorylates and inactivates, Opposite of NHFSA, it is active when phosphorylated
47
Acetyl CoA Carboxylase regulation
```
Citrate attaches to polymerize/activate, palmitoyl attaches to inactivate by depolymerization,
NHFSA
Inactivated by AMP-Kinases
Inhibited by ADP
HECA HECA
```
48
Pyruvate carboxylase
Pyruvate to OAA for FAS
49
Pyruvate carboxylase regulation
Acetyl CoA positive allosteric
| Activated by High Energy Charge (HECA!)
50
PEPCK function + Regulation
OAA to PEP - phosphorylate and decarboxylate
| Inhibited only by high ADP
51
FBPase 2 function + regulation
against PFK2 to break down F-2,6-P, Opposite of NHFedSA, it is active when phosphorylated
Part of 2 part enzyme, other half is PFK2
52
Glucose-6-Phosphatase location, function
Removes phosphate from G-6-P
Only exists in liver so glucose --> Blood!
G-6-P in muscle goes right to glycolysis
53
Lactate Dehydrogenase function and regulation
Anaerobic respiration.. Pyruvate + NADH --> Lactate + NAD+
More NADH = positive
Less NADH = negative
Oxygen present?
54
Cholesterol made where?
Liver
55
Requirements for cholesterol synthesis
Acetyl CoA - thioester bonds
ATP
NADPH
O2
56
Mnemonic for Cholesterol
Alcoholic's Anonymous Has Me Insane and Dying, I'D Go For Some Sweet PinaColada Laced Cocaine
57
LDL receptors undergo ___
Receptor mediated endocytosis
58
LDL receptors if mutated
LDL production will increase abnormally
59
Statin Drugs which step interfers
HMG-CoA Reductase
| Competitive inhibitors!
60
HMG-CoA Reductase regulation
Phosphorylation by AMPKinases, HECA
Degradation - half life is 3 hrs - if Cholesterol is HIGH
Transcription/Translation by SCAP, SREBP, SRE - ONLY IF Cholesterol is LOW
61
SCAP SREBP SRE mechanism
SCAP and SREBP on membrane, if low cholesterol detected, they go into a golgi and go to nucleus where SREBP binds to SRE on chromosome and activates production of HMG-CoA
62
HDL
Reverse cholesterol transport- brings back cholesterol from vascular tissue to return to lver
63
Trans fat vs Saturated fat
Trans fat lowers HDL and raises LDL. Saturated Fat raises LDL but ignores HDL
64
Are there glucagon receptors in muscle?
No, only the liver responds to I/G ratio
65
Glycogen phosphorylase cleaves glycogen at the _________ ends
non-reducing ends
66
Transferase in glycogen degradation
transfers 3 glucoses before a branch point to the non-reducing end of a 1,4 linkage
67
Alpha-1,6-Glucosidase
for branch point cleavage
68
Phosphoglucomutase
Converts G-1-P from glycogen degradation to G-6-P using serine to hold the phosphate
69
Glycogen phosphorylase a and b, T and R forms in muscle and liver
aR=most active + phosphorylated
bT form in muscle, can become bR form with AMP
aR form in liver, can become aT form (less active) with increased glucose
70
Why allosteric and hormonal regulation of glycogen degradation
allosteric is faster than hormonal, so can respond to smaller and quicker changes in glucose homeostasis
71
Precursors for GNG
Lactate, AAs (muscle), Glycerol from TAG breakdown, TCA cycle intermediates (OAA)
72
Cori Cycle main idea
Lactate from muscle moved to liver to be remade into pyruvate for glucose production
Lactate recycling
73
Alanine aminotransferase
Converts alanine to pyruvate by removing an amino group
74
Glycerol processed into GNG how?
Glycerol kinase then glycerol phosphate dehydrogenase to DHAP --> enters as intermediate
75
Can Fatty acids be used as substrates for gluconeogenesis?
NO! They yield acetyl-CoA
| No reverse for pyruvate dehydrogenase, kinetically or themodynamically
76
GNG big picture:
Pyruvate to OAA
OAA leaves mitochondria as aspartic acid or malate
OAA to PEP by PEPCK
PEP to glucose
ATP comes from oxidation of fatty acids or ketone bodies
77
Pyruvate carboxylase
Biotin for any carboxylase!
| Pyruvate + ATP + CO2 --> OAA + ADP + Pi + 2H+
78
PEPCK (Carboxykinase)
OAA + GTP --> PEP + GDP + CO2
| Opposite Pyruvate kinase
79
F-1,6-Bisphosphatase
Hydrolysis of F-1,6-bisphosphate to F-6-P
Opposite PFK1
Inhibited by F-2,6-Bisphosphate
RATE LIMITING POINT in GNG
80
Glucose-6-Phosphatase in GNG, not Glycogen deg.
Not in muscle, only liver
| Converts G-6-P to Glucose, released to bloodstream
81
When does FA oxidation happen?
Fasted state, low I/G
82
3 lipases in FA Oxidation
```
Adipose Triglyceride lipase
Hormone Sensitive lipase
Monoacylglyceride Lipase
Each cleaves a single FA
AHM
```
83
Activation of lipases in FA Oxidation
Phosphorylated perilipin activates ATGL
HS Lipase phosphorylated by Protein Kinase A
Protein Kinase A
Protein Kinase A
84
Albumin role in FA oxidation
Serum protein
Binds multiple fatty acids
Transports FAs to tissues since FAs are hydrophobic
85
Carnitine Acyltransferase I and II
1 attaches carnitine to activated FA - CoA removed
| 2 removes carnitine - adds CoA back
86
Translocase of FA-carnitine
Moves FA-Carnitine into matrix of mitochondria
87
Beta oxidation process:
1. Oxidation = double bond formation, FAD reduced
2. Hydration = alcohol formation
3. Oxidation to yield ketone, NAD+ reduced
4. Add SH to make Acetyl CoA and a Fatty acid CoA to continue oxidation
88
How many ATP does 1 palmitic acid yield
106, not 108, since 2 ATP are required for activation
89
Carnitine Acyltransferase regulation
Inhibited by Malonyl CoA - Cannot make and break down FA's at the same time...
90
FA Oxidation regulation
High [FA] = stimulates
| ATP utilization controls rate of ETC - regulates oxidative enzymes of TCA cycle and beta-oxidation (NAD+ and FAD)
91
Ketone body formation process:
2 Acetyl CoA --> Acetoacetyl CoA --> HMG-CoA --> Acetoacetate --> Acetone and D-3-hydroxybutyrate
Acetone is exhaled
92
Advantages of ketone bodies
Water soluble
fuel source during prolonged fasting - for brain
Muscle sparing during fasting
93
Conditions for Ketosis
Low insulin, low carb diets, Type 1 diabetes, Chronic alcoholism
94
Oxidation of ketone bodies
Ketone body --> acetoacetate --> Acetoacetyl CoA --> 2 Acetyl CoA
Succinyl CoA used
95
Can liver use ketone bodies?
Liver produces ketone bodies but CANNOT oxidize them!!
96
Cholera toxin
cAMP continuously produced - dehydration - diarrhea
97
Energy charge equilibrium maintained by enzyme:
Adenylate Kinase
| 2 ADP ATP + AMP
98
Step 6 of Glycolysis
Redox reaction with NAD+ to form 1,3-BPG and NADH
| 1,3-BPG has high phosphoryl transfer potential (substrate level phosphorylation)
99
Fructose-2,6-Bisphosphate effect on PFK1
Can override the inhibition of high ATP!
100
Pyruvate dehydrogenase complex reaction
2 Pyruvate + NAD+--> CO2 + Acetyl CoA + NADH
101
Vitamin coenzymes of PDC
Thiamine PPi - decarboxylation - releases CO2
Lipoamide - binds acetyl group, attaches CoA group
FAD -- oxidizes Lipoamide
102
Can I keep selling sex for money officer?
Citrate, Isocitrate, a-ketoglutarate, succinyl CoA, Succinate, Fumarate, malate, oxaloacetate!
103
Citrate Synthase
Condensation reaction between OAA and Acetyl CoA - ORDERED BINDING
OAA binds 1st to create site for Acetyl CoA!
104
What drives citrate synthase reaction?
Hydrolysis of high energy thioester bond of acetyl CoA
105
Why is isocitrate dehydrogenase the rate limiting enzyme of TCA
1st step to produce NADH, depends on ETC to return NAD+
| CO2 is removed
106
Regulation within the TCA Cycle
Generally HECI, no hormonal control!
Citrate synthase controlled by small [OAA]
Inhibited by high NADH, low NAD+
107
Anapleurotic reaction
Filling up / Refilling reactions
108
E0 is positive when
The thing will accept electrons, like Oxygen
109
Complex 1
Proton pumps
| NADH --> FMN, 4 H+ pumped per 2 e- passed to CoQ
110
Complex 2
Accepts from FAD
| No proton pumping
111
Isoprene units also appear in ____
not only cholesterol but also CoQ in ETC
112
Complex 3
Transfers from CoQ to oxidized cytochrome c
| pumps 2H+
113
Complex 4
transfers from cytochrome c to oxygen to make water
| Pumps 4 H+
114
Cyanide, Azide, CO inhibit which complex
Complex 4
CN and N3 with Fe 3+ of heme a3
CO with Fe2+ of heme a3
115
Reactive O2 species
OH radical most reactive
| When O2 accepts a single electron to form superoxide
116
Superoxide dismutase
Superoxide dismutase turns superoxide to H2O2
117
Catalase (peroxisomes)
Turn H2O2 to H2O and O2
118
GSH (glutathione) peroxidase and reductase
SH groups act as nucleophiles
React with peroxide to give GSSG
Reductase breaks GSSG back to GSH using NADPH
119
Nonenzymatic antioxidants
Vitamin E - Protects against lipid peroxides
| Vitamin C - supports reduced form of Vitamin E
120
Number of ATP for NADH and FAD
2. 5 ATP for NADH
| 1. 5 ATP for FAD
121
Subunit a vs. alpha
Subunit a has 2 half channels, alpha subunits are just spacers between beta subunits
122
Conformations of beta subunits
L - Loose - binds ADP and Pi
T - Tight - turns ADP + Pi To ATP, but holds it
O - open - releases ATP
123
Amino acid on C subunits in c ring
Aspartic acid
124
ATP yield per glucose from complete oxidation
Invest 2, get out 32, net yield is +30 ATP
125
Glycerol-3-phosphate shuttle
Located in muscle, brings electrons from cytosol to ETC
| Yields 1.5 ATP per NADH instead of 2.5 since it uses FAD
126
Malate Aspartate shuttle
Located in liver/heart
| Still uses NADH so 2.5 ATP are yielded still per NADH
127
Respiratory control
ADP concentration controls rate of O2 consumption
128
As ATP is used...
O2 consumption increases, pmf can be sensed and must be maintained, everything speeds up
129
ATP-ADP translocase
Most ATP to cytoplasm, ADP to mitochondria
130
Respiratory inhibitors
```
Rotenone + Amytal - C1
Antimycin A - C3
CN-, N3-, Fe3+ heme a3 on C4
CO - Fe2+ on heme a3 on C4
Buildup of NADH
```
131
ATP Synthase inhibitors
Oligomycin
DCCD
Same thing happens as respiratory inhibitors, whole process of ETC slows
Buildup of NADH
132
Uncouplers
p-nitro phenol
If stuff is still running, then this is probably it
Buildup of NAD+ but no ATP generated
133
UCP-1 found in...
Brown Adipose tissue only
134
Why use glycogen, in terms of osmotic pressure
Glycogen has a fraction of osmotic pressure vs. equivalent #glucose molecules
135
Alpha vs. beta linkages
```
Alpha = trans - Glycogen
Beta = Cis - Cellulose
```
136
Ketone + Alcohol =
Hemiketal
137
Glycogenin is a protein that...
Synthesizes the primer of glycogen synthesis - a short oligosaccharide of glucose
138
Activation step of glycogen synthesis driven by:
Cleavage of pyrophosphate
| UTP + G-1-P --> UDP-Glucose + PPi
139
AKT effect on glycogen
AKT from insulin signalling
| AKT deactivates glycogen synthase KINASE, which allows glycogen synthase to be active in dephosphorylated form
140
Fatty acid synthesis location
Liver, also adipose tissue to lesser extent
141
What happens without insulin to Acetyl CoA
Ketone bodies are made instead of fatty acids
142
Sources of NADPH
PPP - Glucose to Ribulose 5-c Sugar, gives 2 NADPH
| Malic Enzyme - Malate to pyruvate - gives 1 NADPH
143
What breaks down citrate in cytosol?
ATP Citrate lyase
144
AMP kinases
Phosphorylate and deactivate carboxylases and HMG CoA Reductase
Activated by AMP
Inhibited by ATP
145
Fatty Acid Synthesis Process:
1. Condensation to release CO2
2. Reduction of Carbonyl to get alcohol
3. Dehydration to yield water
4. Reduction of Double bond
5. Pass to condensing enzyme to continue
146
Source of carbons for FAS
Carbon from DIET
147
Where does saturated-->unsaturated bond happen?
Endoplasmic reticulum
148
Glucose-6-Phosphate Dehydrogenase
G-6-P --> some intermediate
| Rate controlling step of PPP, generates 1 NADPH
149
Triacylglycerols - Why make them?
Hydrophobic, efficient storage, energy WITHOUT NITROGEN
150
Sources of glycerol
Adipose tissue depends on DHAP from glycolysis ONLY
| Liver gets it from glycerol kinase
151
Common intermediate between Phospholipid vs. TAG biosynthesis
Phosphotidate
152
Lipoprotein Lipase
During FED state, activated by insulin
153
LDL, HDL, VLDL, Chylomicrons Relative densities and protein concentrations
Density and [TAG] = Chylomicrons>VLDL>LDL>HDL
| Protein Content = HDL>LDL>VLDL>Chylomicrons
154
Thiolase
condenses acetyl coa + acetyl coa to acetoacetyl coA
155
How many ATP from palmitic acid
```
10 for each acetyl coA through TCA
8*10 = 80
split it 7 times in beta oxidation - 4 ATP each
7*4 = 28
Invested 2 carbons
108-2 = 106 ATP
```
156
What do you need for Cholesterol synthesis
ATP for Isoprene unit formation
NADPH for Mevalonate formation and Cyclization and hydroxylation
O2 for Cyclization and hydroxylation
157
Where does cyclization of Cholesterol occur?
Smooth ER
158
Only 5 enzymes that are activated by phosphorylation
```
FBPase-2
Glycogen phosphorylase
Perilipin
HS Lipase
AMPKinase
```
159
Fatty Acid Oxidation regulated by:
Rate of oxidation of NADH and FADH2 in TCA cycle
ATP/ADP ratio - BECAUSE TCA CYCLE DEPENDS ON IT TOO
Malonyl CoA inhibits
High fatty acids activates
160
Rate limiting enzyme of TAG degradation
HS lipase- phosphorylated and activated by PKA
161
Rate Limiting enzyme in FA Oxidation
Carnitine palmitoyl transferase 1
Inhibited by malonyl CoA
162
Glyceraldehyde 3-phosphate dehydrogenase
Step 6 Glycolysis, makes 1,3-BPG
NAD+ --> NADH
Thioester intermediate!
NOT FBI by ATP!
163
What type of reaction does PDH Complex catalyze?
Oxidative decarboxylation
| Pyruvate --> CO2 + Acetyl CoA
164
Citrate synthase binding, be specific
Independently is NOT equal to "induced fit"
ORDERED BINDING..
Also FBI by Citrate!
165
Pantothenic Acid is a coenzyme for
Acyl Carrier Protein in FAS
166
What drives condensation reactions in Lipogenesis?
Decarboxylation, not NADPH
167
Fatty acids produced from ______ end to _______ end
Omega (reducing) to Carboxylic acid end (non-reducing)
