MSK - Biochemistry - Glycolysis; Gluconeogenesis; Glycogen Metabolism Flashcards
(151 cards)
1
Q
How many reactions occur in glycolysis?
What phase are the first 5 known as?
What phase are the second 5 known as?
A
10;
the investment/preparatory phase;
the payoff phase
2
Q
What are the two goals of the investing/preparatory phase of glycolysis?
How many ATP are invested at this point?
A
- To make the process irreversible
- To split the 6-carbon sugar into two 3-carbon sugars
2
3
Q
By the end of the glycolytic investing/preparatory phase, glucose has been split into two molecules known as:
A
Glyceraldehyde-3-phosphate
4
Q
In the second five glycolytic reactions, the payoff phase, what high energy molecules are produced?
What is the net gain of glycolysis?
A
4 ATP, 2 NADH;
2 ATP, 2 NADH
5
Q
Of the ten glycolytic reactions, which are the most important for a healthcare provider to know?
A
1, 3, 6, 7, (9), 10
6
Q
The GLUT transporters work via what type of transport?
A
Facilitated diffusion
7
Q
What GLUT transporters are found in virtually all mammalian tissues and maintain basal glucose levels?
A
GLUT1, GLUT3
8
Q
What GLUT transporter is found in liver and pancreatic cells (as well as the basolateral portion of epithelium in the small intestine) and removes excess glucose from the blood / controls insulin secretion?
A
GLUT2
9
Q
What GLUT transporter is found in muscle and fat cells and is insulin sensitive?
A
GLUT4
10
Q
What GLUT transporter is found in mucosal membranes and spermatozoa for fructose transport?
A
GLUT5
11
Q
GLUT1 and GLUT3 are found in what tissues?
What is their purpose?
A
Virtually all mammalian tissues - maintain cellular basal glucose needs
12
Q
GLUT2 is found in what tissues?
What is its purpose?
A
Pancreatic tissues - control insulin secretion;
Liver and small intestinal tissues - removes excess glucose from blood
13
Q
GLUT4 is found in what tissue(s)?
It is ________-sensitive.
A
Muscle and adipose;
insulin
14
Q
GLUT5 transporters move what substance?
A
Fructose
15
Q
For GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5, state the relative Km for each.
(place them in order of increasing Km)
A
GLUT3 - 1 mM
GLUT1 - 1 - 2 mM
GLUT4 - 5 mM
GLUT5 - 10 mM
GLUT2 - 15 - 20 mM
16
Q
Normal physiological glucose levels are around: ____mM.
A
5.5
(100 mg/dl)
17
Q
Which GLUT transporters are transporting glucose almost all the time?
Which GLUT transporters are transporting glucose in the well-fed state only?
A
GLUT1, GLUT3, GLUT4;
GLUT2
(note: GLUT5 transports fructose)
18
Q
Describe the basic steps of insulin secretion.
A
1. Glucose levels rise (GLUT2 Km = 15 - 20 mM)
2. GLUT2 transporters allow glucose into pancreatic β cells
3. ATP is formed via glycolysis
4. ATP turns off K+ leak channels
5. The cell depolarizes
6. Calcium floods the cell and insulin is released
19
Q
What is the 3-carbon end product of glycolysis?
A
Pyruvate
20
Q
How do anti-hyperglycemic drugs such as sulfonylureas or meglitinides work?
What drug does the opposite?
A
They close ATP-sensitive K+ channels in pancreatic β cells
(note: these are channels that were pumping K+ into the cell);
diazoxide (treats insulinoma-induced hypoglycemia)
21
Q
Should type I diabetics be given sulfonylureas and/or meglitinides?
Should type II diabetics be given sulfonylureas and/or meglitinides?
A
They shouldn’t. They don’t have β cells;
Yes
22
Q
Where are GLUT4 transporters when glucose levels are low?
Where are GLUT4 transporters when glucose levels are high?
A
Endocytosed;
on the plasma membrane (exocytosed)
23
Q
What is the first step of glycolysis?
Why is this step important (3 reasons)?
A
Hexokinase adds a phosphate to glucose (making G6P).
- Energy investment
- Traps glucose in cell
- Ionic charges increase favorability of subsequent interactions
24
Q
What are substrates and product of the first step of glycolysis/
A
Glucose (+ hexokinase + ATP + Mg2+) –> Glucose-6-phosphate
25
Why is the first step of glycolysis (shown below) a favorable reaction (- ΔG)?
ATP coupling
26
Why is the hexokinase found in the liver (hexokinase IV) called glucokinase?
Does it have any inhibitors?
It only acts on glucose;
yes, F6P
27
What is the [glucose] Km for hexokinase I (or II and III)?
What is the [glucose] Km for hexokinase IV (glucokinase)?
0.05 mM;
5 mM
28
Which is allosterically inhibited by G6P, hexokinase I or glucokinase?
Hexokinase I
29
When GLUT2 transports glucose into liver cells, what effect does this have on glucokinase?
It draws it out of the nucleus
30
Which of the following would inactive liver glucokinase by shuttling it into the nucleus, incoming glucose or liver gluconeogenesis?
Liver gluconeogenesis
31
What happens in step two of glycolysis?
What enzyme is responsible?
G6P is turned into F6P;
phosphohexose isomerase
32
What is the commitment step of glycolysis?
Via what enzyme?
Step 3;
phosphfructokinase-1 (PFK-1)
33
What are the two investment steps of the preparatory phase (1st five steps) of glycolysis?
Steps 1 and 3
34
What are the substrates and main product of the 3rd step of glycolysis?
F6P (+ PFK-1 + ATP + Mg2+) --\> F1,6BP
35
What are some allosteric activators of the third step of glycolysis (shown below)?
AMP, ADP, F2,6BP
36
What are some allosteric inhibitors of the third step of glycolysis (shown below)?
ATP, citrate
37
What effect does F2,6BP have on the third step of glycolysis (shown below)?
What effect does citrate have on the third step of glycolysis (shown below)?
Allosteric activation;
allosteric inhibition
38
What enzyme catalyzes the formation of F2,6BP?
What enzyme catalyzes the breakdown of F2,6BP?
PFK-2;
F2,6BPase -2
39
**True/False.**
PFK-2 and F2,6BPase-2 are two separate domains of the same enzyme and both can be active at the same time.
**False.**
They *are* two separate domains of the same enzyme, but only **one** is active at any one point in time
40
What effect does glucagon have on FBPase-2 activity?
How?
**Increased**;
**phosphorylation** of the enzyme via PKA
41
What effect does insulin have on PFK-2 activity?
How?
**Increased**;
**dephosphorylation** of the enzyme via phosphoprotein phosphatase
42
Does glucagon activate the F2,6BPase-2 or PFK-2 domain?
How?
Does insulin activate the F2,6BPase-2 or PFK-2 domain?
How?
**F2,6BPase-2**, phosphorylation via PKA;
**PFK-2**, dephosphorylation via PPP
43
What effect does glucagon have on F2,6BP levels? How?
What effect does insulin have on F2,6BP levels? How?
Decreased, via PKA --\> F2,6BPase-2 activity;
increased, via PPP --\> PFK-2 activity
44
Does F2,6BP allosterically activate or inhibit glycolysis?
Activate
45
Describe glucagon's overall effects on the following:
PKA or PPP
F2,6BPase-2 or PFK-2
F2,6BP
Glycolysis
Gluconeogenesis
PKA **activity increased**
F2,6BPase-2 **activity increased**
F2,6BP **decreased**
Glycolysis **inhibited**
Gluconeogenesis **stimulated**
46
Describe insulin's overall effects on the following:
PKA or PPP
F2,6BPase-2 or PFK-2
F2,6BP
Glycolysis
Gluconeogenesis
PPP **activity increased**
PFK-2 **activity increased**
F2,6BP **increased**
Glycolysis **stimulated**
Gluconeogenesis **inhibited**
47
What happens in step 4 of glycolysis (starting with F1,6BP)?
What happens in step 5 of glycolysis?
The F1,6BP is chopped into DHAP and glyceraldehyde-3-phosphate;
the DHAP is isomerized into glyceraldehyde-3-phosphate
48
Name an allosteric inhibitor of hexokinase I.
G6P
49
What occurs in step 6 of glycolysis?
Why is this important?
Inorganic phosphate is added to glyceraldehyde-3-phosphate to form 1,3-bisphosphoglycerate;
there are now two phosphates on each molecule, yielding four ATP total in the payoff phase (2 ATP net)
50
In step 6 of glycolysis, inorganic phosphate is added to glyceraldehyde-3-phosphate to form 1,3-bisphosphoglycerate.
What enzyme accomplishes this and what electron acceptor is needed?
Glyceraldehyde-3-phosphate dehydrogenase;
NAD+
51
What steps of glycolysis involve ATP hydrolysis?
What steps of glycolysis involve NADH production?
What steps of glycolysis involve ATP production?
Steps 1 and 3;
step 6;
steps 7 and 10
52
Why is it important that F1,6BP (from an original glucose molecule) is cleaved into two separate halves during glycolysis?
The energy generated in the payoff phase is doubled
53
What is the term that describes the fact that reactions with fairly neutral ΔGs with occur rapidly if very thermodynamically stable reactions occur later in the flow?
(E.g. the less favorable steps 2 and 5 of glycolysis happen readily *because* steps 1, 3, and 10 occur?)
Substrate flux
54
What happens in step 7 of glycolysis?
Via what enzyme?
1,3-Bisphosphoglycerate is turned into 3-phosphoglycerate and ATP is formed;
phosphoglycerate kinase
55
The ATP production in glycolysis is termed \_\_\_\_\_\_\_\_\_\_\_-\_\_\_\_\_ phosphorylation.
This in contrast with __________ phosphorylation.
Substrate, level;
oxidative
56
Which must have a higher energy state, 1,3-bisphosphoglycerate or ATP?
(reaction 7 of glycolysis shown below)
1,3-Bisphosphoglycerate
(used for substrate-level phosphorylation)
57
What happens in step 8 of glycolysis (starting with 3-phosphoglycerate)?
What happens in step 9 of glycolysis?
3-PG is isomerized to 2-PG by PG mutase;
2-PG is dehydrated to phosphoenolpyruvatase by enolase
58
What happens in step 10 of glycolysis?
Via what enzyme?
Phosphoenolpyruvate is turned into pyruvate and ATP;
(substrate-level phosphorylation)
**pyruvate kinase**
59
What glycolytic intermediate is one of the highest energy compounds that we know of?
Phosphoenolpyruvate
| (much higher than ATP or 1,3-BPG)
60
Which must have a higher energy state, phosphoenolpyruvate or ATP?
(reaction 10 of glycolysis shown below)
Phosphoenolpyruvate
(used for substrate-level phosphorylation)
61
What are the three important products of glycolysis?
2 Pyruvate
2 NADH
2 ATP
62
What are the glucose-derived substrates and intermediates of glycolysis (starting at glucose and ending at pyruvate)?
Bold each one that is used for substrate-level phosphorylation to form ATP.
Place an asterisk next to each one that is used for glycolytic NADH production.
[1 Glucose] --\>
G6P --\>
F6P --\>
F1,6BP --\>
GAP\* + DHAP (DHAP --\> GAP\*) --\>
**1,3-BPG** --\>
3-PG --\>
2-PG --\>
**PEP** --\>
[2 Pyruvate]
63
In the liver, what hormone serves to inactivate pyruvate kinase?
Via what enzyme?
Glucagon;
PKA
64
What are some allosteric activators of pyruvate kinase?
What are some allosteric inhibitors of pyruvate kinase?
ADP, phosphoenolpyruvate, F1,6BP;
ATP, acetyl-CoA, long-chain fatty acids, alanine
65
What are some allosteric activators of pyruvate kinase?
ADP, phosphoenolpyruvate, F1,6BP
66
What are some allosteric inhibitors of pyruvate kinase?
ATP, acetyl-CoA, long-chain fatty acids, alanine
67
In the liver, what hormone serves to activate pyruvate kinase?
Via what enzyme?
Insulin;
PPP
68
During the 7th step of glycolysis (shown below), 1,3-BPG can be isomerized to become what substance?
What effect will this have on the blood?
What effect will this have had on glycolytic ATP production?
2,3-BPG;
causes oxygen release from hemoglobin;
one less ATP (because step 7 was skipped)
69
What are the two most common genetic causes of hemolytic anemia?
1. G6PD deficiency
2. Pyruvate kinase deficiency
70
What is the main sign of pyruvate kinase deficiency that is often first seen at high altitudes?
Why does it occur?
Hemolytic anemia;
step 7 of glycolysis is circumvented by 2,3BPG formation
(step 10 is already inhibited by the PK deficiency:
subtrate-level ATP synthesis is stopped, and that's all erythrocytes have for energy production)
71
Why would an individual with COPD have a resultant acidosis?
(2 reasons)
Increase in carbonic acid due to trapped CO2
(respiratory acidosis)
Lack of O2 = pause in oxidative phosphorylation; switch to anerobic glycolysis for energy production --\> lactic acid production
(lactic acidosis)
72
What is the purpose of anerobic acidosis?
To regenerate NAD+
by turning pyruvate into lactate
73
**True/False.**
A patient with severe COPD may present with simultaneous respiratory and metabolic acidosis.
**True**
(O2 deficiency / lactic acidosis --\> metabolic cause;
CO2 buildup --\> respiratory cause)
74
During the day (from about breakfast to midnight) blood sugar comes mostly from what two sources?
During the night (midnight to breakfast), it comes mostly from what source?
Diet, glycogenolysis;
gluconeogenesis
75
How many irreversible steps are there in glycolysis?
So how does gluconeogenesis get around this?
3;
with alternate enzymes (4 of them)
76
Why are the effects of hexokinase, PFK-1, and pyruvate kinase deemed 'irreversible?'
They have such negative ΔGs and are hugely thermodynamically favorable
77
For the most part, gluconeogenesis is just glycolysis in the reverse direction.
How many unique gluconeogenic enzymes are there?
What tissues contain them?
Only 4;
hepatic, kidney, and intestinal epithelial tissues
78
What are normal glucose physiological levels?
(in both mg/dl and mM)
100 mg/dl;
5.5 mM
79
With key exceptions in three steps, gluconeogenesis is basically just ___________ in reverse.
Glycolysis
80
What are the four unique gluconeogenic enzymes?
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase
81
What gluconeogenic enzymes allow the body to skip backwards past the 'irreversible' step 10 of glycolysis (shown below)?
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
82
What gluconeogenic enzymes allow the body to skip backwards past the 'irreversible' step 3 of glycolysis?
Where is this enzyme found?
Fructose 1,6-bisphosphatase;
the cytosol
83
What gluconeogenic enzymes allow the body to skip backwards past the 'irreversible' step 1 of glycolysis?
Where is this enzyme found?
Glucose 6-phosphatase;
the ER
84
What are the first two steps of gluconeogenesis?
*What step of glycolysis and enzyme has this allowed us to reverse?*
**1.** Pyruvate carboxylase combines CO2 + biotin + ATP + pyruvate to make oxaloacetate
**2.** Phosphoenolpyruvate carboxykinase adds GTP to oxaloacetate to release that same CO2 and make phosphoenolpyruvate (PEP);
*Step 10, pyruvate kinase*
85
What step of gluconeogenesis occurs in the mitochondria and requires biotin as a cofactor?
Step 1
## Footnote
*(Pyruvate carboxylase combines CO2 + biotin + ATP + pyruvate to make oxaloacetate)*
86
Identify the cellular compartment where each of the following gluconeogenic enzymes are found:
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase
Mitochondria
Mitochondria, cytosol
Cytosol
Endoplasmic reticulum
87
What tissues have all of the following enzymes?
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase
Liver, kidney, intestinal epithelium
*(Note: adipose tissue has PC and PEP-CK for glyceroneogenesis)*
88
How can G6P access the ER to be acted upon by glucose 6-phosphatase in gluconeogensis?
G6P transporter 1 is found on the ER membrane
89
How many steps does it typically take to convert alanine to pyruvate?
1
90
What is an example of a substrate that can be turned into DHAP and then GAP, a gluconeogenic/glycolytic intermediate?
What is an example of a substrate that can be turned into oxaloacetate, a gluconeogenic intermediate?
What is an example of a substrate that can be turned into pyruvate, a gluconeogenic intermediate?
Glycerol;
some amino acids;
lactate, alanine
91
Most of the glucose made in gluconeogenesis is made from the starting substrate:
Alanine
92
What is the energy expense of gluconeogenesis to produce one glucose molecule?
4 ATP + 2 GTP + 2 NADH
93
What is the main allosteric activator of PFK-1 and allosteric inhibitor of F1,6BPase?
F2,6BP
94
What hormone does the pancreas release in the starved state?
What hormone does the pancreas release in the fed state?
Glucagon (islet α cells)
Insulin (islet β cells)
95
What effect does glucagon have on pyruvate kinase?
Inactivation
| (through phosphorylation via PKA)
96
What effect does acetyl-CoA have on pyruvate carboxylase?
Activation
(for increased oxaloacetate to be available in gluconeogenesis or the TCA)
97
A high **glucagon : insulin** ratio stimulates the synthesis of what compounds?
A high **insulin : glucagon** ratio stimulates the synthesis of what compounds?
Pyruvate carboxykinase, F1,6BPase, G6Pase
(gluconeogenic enzymes)
glucokinase, PFK-1, pyruvate kinase
(main glycolytic enzymes)
98
Although adipose tissue cannot perform gluconeogenesis, it still has the first two enzymes of gluconeogenesis (pyruvate carboxylase and PEP carboxykinase).
Why is that?
They are used to synthesize glycerol 3-phosphate from pyruvate
(glyceroneogenesis)
99
How many fatty acids can be attached to one glycerol molecule?
Three
| (to make a triglyceride)
100
What effect does glucagon have on serum fatty acid levels?
They increase dramatically
101
In which organs does glyceroneogenesis occur?
The liver and adipose tissue
102
In what tissues is glycogen synthesized and stored?
The liver and skeletal muscle
103
What enzyme is found in hepatic tissues but not skeletal tissues and explains why muscle does not break down glycogen to maintain blood sugar levels as the liver does?
Glucose 6-phosphatase
(the muscle cannot release its sugar as the liver can)
104
What bond is found in linear glycogen chains?
What bond is found in glycogen branch points?
α-1,4 glycosidic linkages
α-1,6 glycosidic linkages
105
Although glucose is quickly phosphorylated by hexokinase when it enters the muscle (creating glucose 6-phosphate), why is this not yet useful to glycogen synthesis?
So, what is the first step of glycogen synthesis?
Glycogen synthesis starts with glucose 1-phosphate;
G6P is converted to G1P by phosphoglucomutase
106
**True/False.**
The conversion of G6P to G1P by phosphoglucomutase is necessary to glycogen synthesis and thus irreversible.
**False.**
While it is true that this step is necessary for glycogenesis, the reaction is readily reversible.
107
What are the first two steps of glycogen synthesis?
## Footnote
*(Let's assume a glucose molecule has entered the myocyte through a GLUT4 transporter and just been phosphorylated to G6P by hexokinase I)*
**1.** G6P --\> G1P (via phosphoglucomutase)
**2.** G1P --\> UDP - glucose (via UDP-glucose pyrophosphorylase\*)
*(Note\*: 2 phosphate groups were hydrolyzed from UTP and UMP was attached to G1P to form UDP-glucose)*
108
What are the first two enzymes of glycogenesis?
What is the third step?
Phosphoglucomutase;
UDP-glucose pyrophosphorylase;
UDP-glucose --\> added to glycogen (α-1,4 glycosidic bond)
109
A deficiency of what enzyme causes type 0 glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
Glycogen synthase;
the liver;
hypoglycemia, elevated ketones,
early death
110
A deficiency of what enzyme causes type I glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(von Gierke's) glucose 6-phosphatase;
the liver;
hepatomegaly, kidney failure
111
**True/False.**
von Gierke's disease affects skeletal muscle and hepatic tissues.
**False**.
Skeletal muscle lacks glucose 6-phosphatase;
type I glycogen storage disease affects the liver and kidney
112
A deficiency of what enzyme causes type II glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
*(Note: has infantile, juvenile, and adult presentations)*
(Pompe's) lyosomal glucosidase;
skeletal and cardiac muscle;
* infantile form* - death by age 2
* juvenile form* - muscle defects
* adult form* - as a muscular dystrophy
113
A deficiency of what enzyme causes type IIIa glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(Cori's or Forbe's) Debranching enzyme;
the liver, skeletal muscle, cardiac muscle;
myopathy, infantile hepatomegaly
114
Type IIIb glycogen storage disease is similar to type IIIa (Cori's or Forbe's) with what key exception?
It is a deficiency of debranching enzyme in the liver _only_
(presents only as infantile hepatomegaly)
115
A deficiency of what enzyme causes type IV glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(Anderson's) Branching enzyme;
the liver, skeletal muscle;
hepatosplenomegaly, myoglobinuria
116
A deficiency of what enzyme causes type V glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(McArdle's) Glycogen phosphorylase [in muscle];
skeletal muscle;
exercise-induced cramps, myoglobinuria
117
A deficiency of what enzyme causes type VI glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(Hers's) glycogen phosphorylase [in the liver];
the liver;
hepatomegaly
118
What differentiates McArdle's disease from Hers's disease?
Location;
McArdle's - glycogen phosphorylase **in skeletal muscle** is deficient
Hers's - glycogen phosphorylase **in the liver** is deficient
119
A deficiency of what enzyme causes type VII glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(Tarui's) PFK-1 [in muscle];
Muscle, erythrocytes;
Same as McArdle's + hemolytic anemia
120
A deficiency of what enzyme causes type XI glycogen storage disease? (state the alternate name if there is one)
Identify any majorly affected organs.
What are the main signs/symptoms?
(Fanconi-Bickel) GLUT2;
liver;
failure to thrive, hepatomegaly, rickets, kidney dysfunction
121
Name the alternate name (if applicable) and missing enzyme for each of the following glycogen storage diseases:
Type 0
Type Ia
Type II
Glycogen synthase;
(von Gierke's) glucose 6-phosphatase
(Pompe's) lysosomal glucosidase
122
Name the alternate name (if applicable) and missing enzyme for each of the following glycogen storage diseases:
Type IIIa
Type IIIb
Type IV
(Cori's or Forbe's) Debranching enzyme
Liver debranching enzyme
(Anderson's) Branching enzyme
123
Name the alternate name (if applicable) and missing enzyme for each of the following glycogen storage diseases:
Type V
Type VI
(McArdles's) Muscle glycogen phosphorylase
(Hers's) Liver glycogen phosphorylase
124
Name the alternate name (if applicable) and missing enzyme for each of the following glycogen storage diseases:
Type VII
Type XI
(Tarui's) Muscle PFK-1
(Fanconi-Bickel) GLUT2
125
What is the techinical name for the branching enzyme of glycogenesis?
What type of bond does it form between UDP-glucoses?
Glycosyl 4,6 transferase;
α-1,6 glycosidic linkages
126
**True/False.** (for each of the following)
The branching of glycogen (A) increases storage space, (B) increases the number of ends and thus the speed with which it can be stored or broken down, and (C) decreases its solubility.
**A.** True
**B.** True
**C.** False; branching increases solubility
127
*De novo g*lycogenesis needs a starting point and can't just start as free-floating UDP-glucose molecules.
What is the primer protein that serves as this initialization point?
Glycogenin
128
Anderson's disease affects what organ tissues?
(type IV glycogen storage disease)
hepatic tissue and skeletal muscle
129
What enzyme chops single G1P molecules from glycogen in a linear manner?
What is this enzyme's cofactor?
Glycogen phosphorylase;
Pyridoxal phosphate (vitamin B6)
130
What are the four primary enzymes of glycogenesis?
In *de novo* glycogenesis, they build off what **primer**?
Phosphoglucomutase;
UDP-glucose pyrophosphorylase;
glycogen synthase;
Glycosyl 4,6 transferase (branching enzyme)
**glycogenin**
131
Describe the two steps of glycogen debranching during glycogenolysis.
Name the two enzymes involved
**1.** 3 G1P residues are transfered from the branch, leaving just one at the branch point (enzyme: **glucosyl 4,4-transglycosidase**)
2. **α-1,6 glucosidase** cleaves the remaining G1P
132
Lysosomal acidic α-glucosidase is the equivalent of what other enzyme (but found in the lysosome instead)?
Similar to this other enzyme, it cleaves what type of bond?
Glycogen phosphorylase;
α-1,4 glycosidic linkages
133
Name all four enzymes of glycogenolysis that take branched glycogen and turn it into G6P molecules.
Glycogen phosphorylase;
\*glucosyl 4,4 transglycosidase;
\*α-1,6 Glucosidase;
phosphoglucomutase
*(\*both part of debranching enzyme)*
134
What cofactor does glycogen phosphorylase require?
It is basically the active form of vitamin \_\_.
Pyridoxal phosphate;
B6
135
Which of the following is activated by phosphorylation and which is deactivated by phosphorylation?
Glycogen synthase
Glycogen phosphorylase
**Activated**: glycogen phosphorylase
**Inactivated**: glycogen synthase
136
Via what covalent modification is glycogen synthase activated?
What hormone would likely result in this effect?
Dephosphorylation;
insulin (and PP1 --\> inactivating glycogen synthase kinase 3)
137
Via what covalent modification is glycogen phosphorylase activated?
What hormone would likely result in this effect?
Phosphorylation;
glucagon/epinephrine (and PKA --\> activating phosphorylase kinase)
138
What molecule, at high concentrations, will allosterically inactivate glycogen phosphorylase?
Glucose
139
Why do individuals with pyruvate kinase deficiency often manifest with hemolytic anemia at high altitudes?
*(Hint: steps 7 and 10 of glycolysis are the only ATP-producing mechanisms that RBCs have)*
As 1,3-BPG is isomerized to 2,3-BPG (because of the altitude), the afflicted individual loses their only remaining ATP-production step of glycolysis (step 7)
(step 10 is already compromised by the pyruvate kinase deficiency)
140
**True/False.**
Erythrocytes in patients with pyruvate kinase deficiency are getting all their ATP from _only_ step 10 of glycolysis.
**False.**
The RBCs are getting all their ATP from only *step 7*
(step 10 is compromised by the PK deficiency)
141
How does 2-deoxyglucose inhibit ATP production and glycolysis?
It is phosphorylated by hexokinase and then builds up in the cell as 2-deoxyglucose 6-phosphate
(it cannot progress to the second step of glycolysis)
142
What glycolytic enzyme does iodoacetamide bind and inhibit?
Glyceraldehyde 3-phosphate dehydrogenase
143
What type of phosphorylation does arsenate (a phosphate analog) inhibit?
Substrate-level
144
What glycolytic enzyme does fluoride inhibit?
Enolase
145
Which is allosterically inhibited by F6P, hexokinase I or glucokinase?
Glucokinase
146
Which amino acid is the most common substrate for kinase modification of the proteins that control the rates of glucose catabolism and glycogen formation?
Serine
147
Which enzyme catalyzes a reaction that is most likely to be the *committed* step in the pathway?
E1 --\> E2 --\> E3 --\> E4
**E1 **--\> E2 --\> E3 --\> E4
148
The metabolite of which enzyme is most likely to be feedback inhibitor for the pathway?
E1 --\> E2 --\> E3 --\> E4
E1 --\> E2 --\> E3 --\> **E4**
149
What high-energy bond is broken to induce glycogen storage?
UTP
150
Most steps of glycogenolysis yield G1P monomers.
Which reaction yields unphosphorylated glucose?
Alpha-1,6 glucosidase
| (domain of debranching enzyme)
151
What are the two domains of the debranching enzyme in glycogenolysis?
What is branching enzyme's name?
Glucosyl 4,4-transglycosidase,
alpha-1,6 glucosidase;
glycosyl 4,6 transferase
