Glucose and AA Metabolism Flashcards
(177 cards)
1
Q
What are 4 products that glucose can be turned into and what is each product’s function?
A
- Glycogen, starch, sucrose –> storage
- Pyruvate –> Oxidation via glycolysis
- Extracellular matrix and cell wall polysaccharides –> Synthesis of structural polymers
- Ribose 5 Phosphate –> Oxidation via pentose phosphate pathway
2
Q
What are the 4 pathways of glucose utilization?
A
- Glycolysis - glucose is degraded to pyruvate
- Gluconeogenesis - glucose is formed from a non-COH source
- Glycogenesis - glycogen is polymerized from glucose units
- Glycogenolysis - glycogen is degraded to glucose units
3
Q
What are the two phases of glycolysis?
A
Preparatory phase, payoff phase
4
Q
In the preparatory phase, when do the first and second priming reactions take place?
A
1st: Glucose to G-6-P via hexokinase. ATP used up
2nd: F-6-P to F-1,6-P via PFK-1. ATP used up
5
Q
What is happening as aldolase converts F-1,6-BiP into Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate?
A
Cleavage of 6-C sugar phosphate to two 3-C sugar phosphates
6
Q
What enzyme in glycolysis is also found on FA synthesis? What phase is it found in?
A
Glycerol-3-phosphate dehydrogenase
7
Q
What is special about the conversion of 2NAD(+) –> 2NADH + 2H(+) from (2)Glyceraldehyde-3-phosphate to (2)1,3-Bisphosphoglycerate?
A
The NADH is used as the energy source, not ATP.
Oxidation & phosphorilation!!
8
Q
What is the 1st ATP-forming reaction in glycolysis? The 2nd?
A
1st: (2)1,3-Bisphosphoglycerate –> (2)3-Phosphoglycerate
2nd:
(2)Phosphoenolpyruvate –> (2)Pyruvate
9
Q
What is another way of calling an ATP-forming reaction in glycolysis?
A
Substrate-level phosphorylation
10
Q
Define the Preparatory Phase?
A
Phosphorylation of glucose and its conversion to glyceraldehyde-3-phosphate
11
Q
Define the Payoff phase?
A
Oxidative conversion of glyceraldehyde-3-phosphate to pyruvate and the coupled formation of ATP and NADH
12
Q
What does the initial phosphorylation of glucose ensure?
A
That the pathway intermediates remain in the cell.
13
Q
In the 1st step of glycolysis, phosphorylation occurs on which C?
A
C-6
14
Q
In the 1st step of glycolysis, why does phosphorylation not occur on C-1?
A
C-1 is a carbonyl group and can not be phosphorylated.
15
Q
Isomerization from G-6-P to F-6-P does what exactly?
A
It moves the carbonyl to C-2. Now C-1 is a hydroxyl group that can be later phosphorylated.
16
Q
From F-6-P to F-1,6-BiP, phosphorylation occurs on what C?
A
C-1
17
Q
What does the relocation of the carbonyl group onto C-2 facilitate?
A
C-C bond cleavage at the right location to yield two 3-Carbon products.
18
Q
What reaction occurs to split Fructose-1,6-biphosphate into two 3-carbon compounds?
A
Reverse of an aldol condensation
19
Q
What is the oxidative phosphorylation of Glyceraldehyde-3-phosphate a prerequisite for? What is produced?
A
ATP production. NADH is produced.
20
Q
What happens from 3-Phosphoglycerate to 2-phosphoglycerate. What does this do?
A
The remaining phosphoryl group moves from C-2 to C-3. This sets up the final steps of the pathway.
21
Q
What happens between 2-Phosphoglycerate and Phosphoenolpyruvate? What does this do?
A
Dehydration which activates the phosphoryl for transfer to ADP in the final step.
22
Q
During what steps in the payoff phase is ATP produced? NADH produced?
A
ATP
- 1,3-Biphosphoglycerate –> 3-Phosphoglycerate
- Phosphoenolpyruvate –> Pyruvate
23
Q
Net Yield formula of Glycolysis
A
1glucose + 2ATP + 2NAD(+) + 4ADP + 2Pi = 2Pyruvate + 2NADH + 2H(+) + 2ATP + 2H2O
24
Q
How many ATP’s are used during Preparatory phase? How many ATP’s are produced during the Payoff phase? Net?
A
- 2
- 4
- 2
25
What are the 3 different paths that the 2 Pyruvate produced from glycolysis can take?
1. 2 Ethanol + 2 CO2
2. Acetyl-CoA --> 4 CO2 + 4 H2O
3. 2 Lactate
26
Under what conditions does pyruvate turn into 2 Ethanol + 2 CO2?
Hypoxic or anaerobic conditions.
| Fermentation to ethanol and yeast.
27
Under what conditions does pyruvate turn into 2 Acetyl-CoA, what else is producted? What pathway does it then go through to become 4CO2 + 4H2O?
Aerobic conditions, 2CO2 are also produced.
Citric acid cycle.
28
Under what conditions does pyruvate turn into 2 Lactate? Where does this normally happen in nature?
Anaerobic conditions.
Vigorously contracting muscle, erythrocytes, some microorganisms. Happens when animal tissues cannot be supplied with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis
29
Which type of cells produce lactate from pyruvate even under aerobic conditions? Via which enzyme?
Erythrocytes (have no mitochondria). Vial lactate dehydrogenase
30
How does lactate dehydrogenase modify pyruvate? Draw it.
Forms the L-isomer of lactate: L-lactate.
31
What is the change in free energy of the Pyruvate --> Lactate reaction? What does this mean?
-25.1 kJ/mol. Lactate formation is strongly favored.
32
What is the net production of NADH in lactate formation from pyruvate?
Because 2 molecules of NADH were produced in the payoff phase of glycolysis, there is no net production of NADH. Glycolysis produces 2NADH, then fermentation uses those two NADH.
33
When oxygen is not available in animal cells...
1. NAD+ is required for glycolysis to continue.
2. NAD+ is generated by converting pyruvate to lactate.
3. Erythrocytes convert pyruvate to lactate then carry the lactate to the liver where it is converted to glucose during muscle recovery.
34
What are the 5 primary sources of glucose into the preparatory stage of glycolysis? What are their enzymes?
Lactose (lactase), Trehalose (trehalase), Sucrose (sucrase), Dietary glycogen/starch (alpha-amylase), Endogenous glycogen (phosphorylase)
35
Where does the digestion of starch begin in our body? What enzyme is present and what does it do?
In the mouth. Alpha-amylase hydrolyzes the (alpha-1,4) glycosidic linkages of starch. Water is used!! (not Pi)
36
Where does alpha-amylase become inactivated in the body?
Stomach because of low pH. New alpha-amylase gets secreted by the pancreas into the small intestine.
37
What does dietary glycogen/starch become before it becomes G-6-P?
Dietary glycogen/starch (alpha-amylase) --> D-Glucose (hexokinase) --> Glucose-6-phosphate.
38
During glcogenolysis, what part of the glycogen molecule becomes broken down into glucose? What enzyme activates this reaction?
The non-reducing end of the glycogen molecule. Enzyme: glycogen (starch) phosphorylase.
39
What are the two products of glycogenolysis?
Glucose-1-phosphate +
| Glycogen (n-1) glucose units.
40
For what 6 body systems is glucose the main/only source of fuel?
Brain, nervous system, erythrocytes, testes, renal medulla, and embryo tissue.
41
When is
| gluconeogenesis required? 3 examples?
When glucose stores are not sufficient/depleted. Between meals, during long fasts, after vigorous exercise (needed for recovery).
42
What does gluconeogenesis do?
Converts pyruvate and related 3- & 4- C compounds to glucose. Basically reverse glycolysis.
43
In what 3 locations does gluconeogenesis take place in the body? Which is the main spot?
Liver (majority), renal cortex (cortex of kidney), and epithelial cells that line the small intestine.
44
What happens to the lactate produced by anaerobic glycolysis in skeletal muscles after vigorous exercise? What is another name for this process?
It goes back to the liver where it is converted to glucose via gluconeogenesis. This glucose then travels back to the muscles & is converted to glycogen. Cori cycle.
45
What 3 steps of gluconeogenesis use different enzymes than glycolysis?
1. Pyruvate --> Phosphoenolpyruvate
2. Fructose-1,6-bisphosphate --> Fructose-6-phosphate
3. Glucose-6-phosphate --> Glucose
46
What enzyme is different in gluconeogenesis and glycolysis in the step involving Phosphoenolpyruvate and Pyruvate? At what stage is there an extra intermediate in gluconeogenesis that is not in glycolysis?
Glycolysis:
Phosphoenolpyruvate --> Pyruvate. Enzyme: pyruvate kinase (produces 2 ATP)
Gluconeogenesis:
1. Pyruvate --> Oxaloacetate. Enzyme: Pyruvate carboxylase (2 ADP produced).
2. Oxaloacetate --> Phosphoenolpyruvate. Enzyme: PEP carboxykinase (2 GDP produced + CO2).
47
What is the abreviation for Phosphoenolpyruvate?
PEP
48
Where in the cell does the Pyruvate to Oxaloacetate reaction take place?
Mitochondria
49
Where in the cell does the oxaloacetate to PEP reaction take place?
Cytosol/mitochondria
50
Pyruvate ---> oxaloacetate reaction requires what coenzyme?
Biotin
51
What is biotin?
A vitamin
52
Which intermediates of the TCA cycle can enter gluconeogenesis?
All of them!
53
What is the most common fate of G-6-P? What is an alternative fate?
Glycolysis. Pentose phosphate pathway
54
What is another term for pentose phosphate pathway?
Hexose monophosphate pathway.
55
What is the electron acceptor in the PPP? What does it make?
NADP+ which yeilds NADPH.
56
What type of cells undergo the pentose phosphate pathway? Such as? To produce what?
Rapidly dividing cells. Bone marrow, skin, intestinal mucosa, tumors!
Products: RNA, DNA, ATP, NADH, FADH2, Coenzyme A.
57
What type of cells require the NADPH produced by the PPP? For what 2 reasons do these cells require NADPH?
Tissues that carry out extensive fatty acid synthesis (adipose, liver, lactating mamary glands) or
extensive cholesterol synthesis and steroid hormones (liver, adrenal glands, gonads). Erythrocytes and eye cells.
Needed for reductive biosynthesis or to counter the effects of oxygen radicals.
58
What is the 1st reaction of the PPP + enzyme? Biproduct
G-6-P --> 6-phosphogluconate.
Enzyme: G6P Dehydrogenase.
Biproduct: NADPH
59
What does the NADPH produced in the 1st reaction of the PPP donate its electrons to? What enzyme is involved?
GSSG --> 2 GSH
Enzyme: Glutathione reductase
60
What is the second reaction of the PPP + enzyme? Biproduct?
6-Phosphogluconate --> Ribulose-5-Phosphate.
Enzyme: 6-phosphogluconate-dehydrogenase
Biproduct: NADPH
61
What does the NADPH produced in the 2nd reaction of the PPP donate its electrons to? What is this an example of?
Precursors --> fatty acies, sterols, etc.
Example of reductive biosynthesis
62
What is the 3rd step of the PPP? Enzyme?
Ribulose-5-Phosphate --> Ribose-5-phosphate.
Enzyme: Phosphopentose isomerase.
63
Ribose-5-Phosphate is a precursor for what?
Nucleotide synthesis (Nucleotides, coenzymes, DNA, RNA)
64
Why would tissue cells only undergo the non-oxidative phase instead of the oxidative phase?
They mainly just need NAHPH, not so much nucleotide production
65
What is recycled in the non-oxidative phase of the pentose phosphate pathway? Enzyme?
Ribulose-5-phosphate is recycled to G6P.
Enzyme: Transketolase, transaldolase
66
List the formation stages from O2 to Oxidative damage to lipids, proteins, DNA? What are additives & biproducts along the way?
Oxygen [O2] --> Superoxide Radical [*O2-] --> (((2H+ & e- comes in))) -->
Hydrogen peroxide [H2O2] --> (((H+ & e- come in))) (biproduct: H2O) -->
Hydroxyl Radical [*OH] --> Oxidative damage to lipids, proteins, DNA
67
How does the formation of 2GSH to GSSG prevent oxidative damage? Enzyme?
Adds 2 hydrogens to H2O2 --> 2H2O.
Enzyme: Glutathione peroxidase
68
How does 2GSH prevent oxidative damage?
Binds to [*OH], inhibiting oxidative damage to lipids, proteins, DNA
69
How is the PPP regulated (what inhibits it)? What is the result?
When NADH is forming faster than it is being used for biosyhtnesis and glutathione reduction, [NADPH] rises and inhibits the 1st enzyme in the PPP (G6P dehydrogenase).
Result: G6P is available for glycolysis.
70
Why do some of the reactions of gluconeogenesis use different enzymes at the same step of glycolysis?
Because they are the irreversible reactions of glycolysis: those catalyzed by hexokinase, PFK-1, & pyruvate kinase.
71
What is the change in free energy of glycolysis's irreversible reactions?
Large and negative
72
What 3 signaling molecules regulate expression/function of glycolytic enzymes?
Glucagon, epinephrine, insuline
73
What is the purpose of the regulation of glycolysis?
Maintain a constant ATP level
74
What are the isozymes of hexokinase? How are they all different?
Hexokinase I, II, III, IV.
| Each encoded by a different gene.
75
What is an isozyme?
Multiple forms of an enzyme that catalyze the same reaction but differ in amino acid sequence, substrate affinity, Vmax, and/or regulatory proteins.
76
What are the 3 main characteristics of Hexokinase I & II?
1. Predominant in muscle cells (myocytes)
2. Very high affinity for glucose (activity reaches max saturation quickly)
3. Allosterically inhibited by their product: G6P
77
What does allosteric mean?
Enzyme changes conformation of active site by binding to a site that is not the active site.
78
What is the difference between muscle cells and liver cells in terms of glucose usage?
Muscle cells: consume glucose & use it for energy production
Liver cells: maintain glucose homeostasis by consuming or producing glucose depending on the current [blood glucose]
79
What is a liver cell called?
Hepatocyte
80
What are the 3 characteristics of hexokinase IV?
???????????
1. Predominant in the liver
2. Low affinity for glucose. You need 5x the normal [glucose] for hexokinase IV to be fully saturated. At high [blood glucose] hexokinase IV is not fully saturated so continues to produce G6P. At low [blood glucose], the glucose generated by gluconeogenesis leaves the cell before affected by hexokinase, because the affinity is so low. ??????
2. It is not inhibited by G6P
3. Hexokinase IV can be inhibited by a regulatory protein (GKRP) & kept in nucleus when [fructose-6-phosphate] is high. When Glycolysis is activated, high [glucose] outcompetes F-6-P, & releases hexokinase IV to the cytosol.
81
What is special about PFK-1 (Phosphofructokinase-1)?
It commits glucose to glycolysis. Major point of regulation
82
What inhibits PFK-1? Activates it?
Allosteric inhibitors: ATP & citrate. The major role of glycolysis is to produce ATP, so when there is enough = inhibits.
Allosteric activators: High [AMP] & [ADP] + F-2,6-P
83
What inhibits FBPase-1 (Fructose Bisphosphatase-1?)
AMP
84
What does insulin promote?
Glycolysis, glycogenesis, and triglyceride synthesis
85
What does glucagon promote? Inhibit?
Promotes gluconeogenesis.
| inhibits glycolysis.
86
What does the secretion of insulin activate? Which enzyme aids this reaction? Biproduct? Required?
PFK-2 via enzyme phospho-protein phosphatase.
Biproduct: Pi
Requires: H2O
87
After its activation via the presence of insulin, what does PFK-2 do? What is PFK-2 dependent on?
it converts F-6-P into F-2,6-P. PFK-2 is ATP dependent, biproduct = ADP.
88
What is special about the presence of Fructose-2,6-phosphate? This leads to???
It's presence activates PFK-1. PFK-1 Converts F-6-P to F-1,6-biP ----> Glycolysis bound!!!
89
What does the secretion of glucagon activate? Which enzyme aids this reaction? Biproduct?
FBPase-2 via enzyme cAMP-dependent protein kinase
Biproduct: ADP
90
After its activation via the presence of glucagon, what does FBPase-2 do? Biproduct?
It converts F-2,6-biP back to F-6-P.
Biproduct: Pi
91
What is special about the absence of F-2,6-biP?
Activates FBPase-1 which converts F-1,6-biP to F-6-P ---> Gluconeogenesis bound!!!!
92
How does Xylulose-5-phosphate regulate glycolysis/gluconeogenesis?
It activates phosphoprotein phosphatase 2A which dephosphorylates the PFK-2/FPBase-2 enzyme, activating PFK-2. This causes a rise in [F-2,6-P] --> glycolysis!!!
Inhibits gluconeogenesis
93
Xylulose-5-phosphate is a product of what pathway?
PPP
94
What allostericaly inhibits the enzyme (pyruvate kinase) in the reaction from PEP-->Pyruvate?
High [ATP, acetyl-CoA, long chain FA]. Also Alanine which is produced from pyruvate via transamination reaction (reversible)
95
What allostericaly activates pyruvate kinase in the PEP-->Pyruvate reaction?
F16BP
96
What enzyme is involved in the PEP-->Pyruvate reaction?
Pyruvate Kinase L/M
97
What is a biproduct of the PEP-->Pyruvate reaction?
ATP = produced
98
What isozyme of Pyruvate Kinase is effected by phosphorilation?
Liver form
99
When is pyruvate kinase L inactivated? What is the mechanism? Effect?
When glucagon is released due to low blood [glucose]. Glucagon activates -cAMP-dependent protein kinase (PKA) which phosphorylates the Pyruvate Kinase L, inactivating it. This slows glucose use as fuel in the liver & allows the glucose to be used in other parts of the body (brain/other organs)
100
When is [acetyl-CoA] high in the liver?
When there is sufficient FA for beta-oxidation
101
How does acetyl CoA act as a regulator of pyruvate?
When [acetyl-CoA] is high, this means that further breakdown of glucose for fuel is not necessary. High [acetyl-CoA] inhibits the pyruvate dehydrogenate complex and activates the pyruvate carboxylase enzyme. This favors production of oxaloacetate and gluconeogenesis!
102
What are the two fates of pyruvate?
1. Acetyl-CoA --> TCA --> energy
| 2. Oxaloacetate --> gluconeogenesis
103
Liver cells:
1. Scientific name?
2. Hexokinase isozyme?
3. Glucose transporter?
1. Hepatocytes
2. Hexokinase IV
3. GLUT 2
104
What does ChREBP stand for? When is ChREBP unable to enter the nucleus?
Carbohydrate response element binding protein. When either its Tyr-P or Ser-P residues are phosphoryated - it remains in the cytosol.
105
What enzyme dephosphoylates ChREBP? Which residue is dephosphorilated first?
What activates this enzyme?
What does this dephosphorilation allow?
Protein phosphatase (PP2A). This allows entry into the nucleus. Ser residue.
Xylulose-5-phosphate
Allows entry of ChREBP into the nucleus.
106
Once into the nucleus, what enzyme further dephosphorylates ChREBP?
Which residue is dephosphorilated?
What does this dephosphorilation cause?
Protein phosphatase -PP2A (activated by Xylulose-5-phosphate)
Thr
ChREBP is now activated and binds to its partner protein Mlx.
107
What does the ChREBP-Mlx complex bind to once it has come together?
ChoRE (carbohydrate response element)
108
What is ChoRE?
A specific DNA sequence that is recognized by the transcription factor.
109
What is the function of the ChREBP-Mlx complex?
Allow the transcription factor to turn on the synthesis of pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase (1st enzyme in the path to fatty acid synthesis)
110
What is the purpose of FOXO1 on the transcriptional regulation of enzymes?
It promotes the synthesis of gluconeogenic enzymes, and suppresses the synthesis of the enzymes of glycolysis + PPP + triacylglycerol synthesis.
111
When is FOXO1 activated?
When it is not phosphorilated
112
What does FOXO1 act as in its unphosphorylated form?
A nuclear transcription factor.
113
What enzyme dephosphorylates FOXO1?
phosphoprotein phosphatase
114
What does FOXO1 do in response to insulin?
It leaves the nucleus and goes into the cytosole where it becomes phosphorilated by PKB, then bound to ubiquitin and degraded by proteasome.
115
What prevents FOXO1 to become phosphorilated by PKB?
Glucagon!!! Allowing it to remain active in the nucleus
116
What happens to FOXO1 that remains unphosphorilated or that becomes dephosphorilated?
In nucleus, it binds to a response element & triggers transcription of PEP carboxykinase, G6P & more...
117
Slide 32
Skipped
118
How do animals store glucose? How do plants store glucose?
1. Glycogen
| 2. Starch
119
In what 2 locations is glycogen primarily found?
Liver and muscle
120
Glycogen makes up what % of the liver's weight?
10%
121
Where is glycogen stored?
Large cytosolic granules
122
What is the elementary particle of glycogen?How many glucose residues is 1 beta-particle made up of? With how many non-reducing ends?
Beta-particle.
55,000 glucose residues! With 2,000 non-reducing ends!
123
How many beta-particles is an alpha-rosette made up of?
20-40
124
How fast are alpha-rosettes depleted after fasting in liver? Depleted after how much exercise in muscles?
12-24 h
1 h
125
Amount of energy stored as glycogen relative to the amount of energy stored as fat?
Waaaaaayyyy less
126
Glycogenesis is predominant in what type of cells?
Liver
127
What is necessary for the polymerization of glucose into glycogen? What do these compounds do?
Sugar nucleotides which activate the anomeric carbon of a glucose molecule by attaching it to a nucleotide via a phospho-ester bond.
128
What sugar nucleotide is used in the production of glycogen? What two molecules is this sugar nucleotide made up of?
UDP-glucose. Made up of D-Glucosyl group + Uridine
129
What is the net reaction of the formation of UDP -glucose?
What acts as the nucleophile in the mechanism? What does this nucleophile attach?
Sugar phosphate + NTP ---> NDP-sugar (sugar nucleotide) + 2Pi
Condensation reaction!!
The neg charged oxygen on the sugar phosphate serves as a nucleophile & attacks the alpha-phosphate of the neucleoside triphosphate.
130
What is the first step in the formation of UDP Glucose? How are 2Pi formed?
Sugar phosphate + NTP --> Pyrophosphate (PPi) + Sugar Nucleotide (NDP-sugar).
^Enzyme: NDP-sugar pyrophosphorylase
Pyrophosphate (PPi) --> 2 Phosphate via enzyme inorganic pyrophosphatase.
131
What is the function of the NDP-sugar pyrophosphorylase enzyme?
Removes 2 Pi's from NTP and adds a sugar phosphate
132
What does the enzyme glycogen synthase need in order to produce a new glycogen molecule?
A primer with at least 8 glucose residues!
133
What two molecules initiate the formation of the primer for glycogenesis?
Glycogenin (a protein) + UDP-glucose
134
What is special about Glycogenin?
It is both the primer on which the new chains are assembled and the enzyme that catalyzes their assembly.
135
What is the very first step in the synthesis of a new glycogen molecule?
What happens next?
Biproduct?
How many times does this process occur?
Transfer of a glucose residue from UDP-glucose to the hydroxyl group (-OH) of Tyr-194 of glycogenin. (The -OH of glycogenin's Tyr-194 attacks the C-1 of UDP-glucose).
The C-1 hydroxyl group of a new UDP-glucose attacks the C-4 of the terminal glucose molecule on the growing glycogen!
Biproduct: UDP
Up until there are 8 glucose residues.
136
How many times does this primer process occur?
8
137
What bonds are formed between the glucose molecules of glycogen? Due to what type of reaction?
(alpha1-->4) glycosidic bonds.
Condensation reaction
138
What is the transfer of a gucose residue from UDP-glucose to the hydroxyl group of Tyr-194 of glycogen catalyzed by?
The protein's intrinsic glucosyltransferase activity
139
What enzyme elongates a glycogen chain? How?
How many glucose residues must already be present in the glycogen chain for glycogen synthase to become activated?
Glycogen synthase. By transffering the glucose residue of UDP-glucose to the non-reducing end of a glycogen branch.
n > 4
140
An newly elongated glycogen has what formula?
n + 1 residues
141
What is another name for the glycogen branching enzyme?
amylo(1-->4) to (1-->6)transglycosylase
142
How many glucose residues down from the terminal one does the glycogen branching enzyme cleave? (textbook)
What glycosidic bond does the glycogen-branching enzyme cleave from the glycogen core?
6-7
4th one
143
What kind of bond is formed at the new branch point during glycogen synthesis?
(alpha1-->6)
144
What is the purpose of branching?
1. Increase solubility
2. Increase the number of non-reducing ends (to increase # of sites accessible to glycogen phosphorylase and glycogen synthase which only act at non-reducing ends)
145
What are the 4 main steps to glycogenesis?
1. Formation of UDP-glucose (NDP-sugar-pyrophosphorylase)
2. Initial short chain synthesis (glycogenin --> up to 8 glucose molecules)
3. Elongation (glycogen synthase)
4. Branching (glycogen-branching enzyme)
146
Each chain of glycogen has approximately how many glucose residues?
12-14
147
What is glycogenolysis?
Glycogen breakdown
148
What are the 3 enzymes involved in glycogenolysis?
1. Glycogen phosphorylase
2. Glycogen debranching enzyme
3. Phosphoglucomutase
149
What reaction does glycogen phosphorylase catalyze? What molecule is produced?
Attach of Pi on the (alpha1-->4) glycosidic linkage of two glucose residues at a non-reducing end of a glycogen molecule.
Glucose-1-phosphate
150
When does glycogen phosphorylase stop repetitively breaking glucose off glycogen?
When it reaches the 4th glucose from a (alpha1-->6) branching point
151
What is an essential cofactor of the glycogen phosphorylase reaction?
Pyridoxal phosphate
152
How are the remaining 4 glucose residues near the branch removed after the terminal glucose residues have been removed by glycogen phosphorylase?
Via a debranching enzyme
153
What is special about the debranching enzyme?
It is bi-functional.
1. Transferase activity
2. (alpha1-->6) glucosidase activity
154
What happens during the transferase activity of the debranching enzyme?
a block of 3-glucose residues is shifted from the branch to the nearest non-reducing end -- reattached in (alpha1-->4) linkage
155
What happens during the (alpha1-->6) activity of the debranching enzyme?
The single glucose residue remaining at the branch point, in a (alpha1-->6) linkage, is then released as free glucose.
156
Which enzyme produces glucose-6-phosphate from glucose-1-phosphate? How?
Where does G-6-P go after?
Phosphoglucomutase. This enzyme has a phosphorilated serine residue which it first donates to C-6 of glucose-1-phosphate, producing glucose-1,6-bisphosphate. The phosphate group on C-1 of glucose-1,6-bisphosphate is then transfered back to the enzyme.
157
What is the function of the G6P formed from glucogenolysis in muscles? In liver?
Muscles: enter glycolysis and serve as an energy source to support muscle contraction
Liver: Release glucose into the blood when blood glucose levels drop
158
What enzyme is required in the liver to convert G6P to Glucose? Where is it located? What kind of protein is this & what organelle does it belong to? Where is its active site located?
Glucose-6-phosphatase.
Liver (& kidney).
Integral membrane protein of the ER.
Active site is on the lumen side of the ER.
159
How is the glucose-6-phosphate produced in the cytosol of the liver enter the lumen of the ER?
T1 specific transporter
160
What is the function of glucose-6-phosphatase?
Hydrolyses G6P into Glucose + Pi
161
How do glucose and Pi leave the lumen of the ER?
T2 - glucose transporter
| T3 - Pi transporter
162
How does glucose leave the hepatocyte?
GLUT2 transporter on plasma membrane
163
What is the purpose of having the active site of G6P inside of the ER lumen instead of in the cytosol?
This separates the reaction from glycolysis that is happening in the cytosol (which would steal G6P)
164
What are the active and inactive forms of the glycogen phosphorylase enzyme?
Active: Glycogen phosphorylase a
Inactive: Glycogen phosphorylase b
165
Where is glycogen phosphorylase b predominantly found in the body?
Resting muscles
166
What enzyme activates phosphorylase b to a? How is it activated?
Phosphorylase b kinase. Epinephrine (in muscle)/glucagon(in liver). Rise in cAMP activates PKA which phosphorylates 'Phosphorylase b kinase' on its 2 serine residues via 2 ATP's --> formation of phosphorylase a kinase (active form) which stimulates glycogen breakdown.
167
What does the activation of phosphorylase a kinase do in muscle vs liver?
Muscle: fuel for glycolysis to sustain fight or flight response signaled by epinephrine
Liver: glycogen breakdown fixes the low blood glucose signaled by glucagon --> releasing glucose
168
What enzyme causes phosphorylase a to become inactivated back to phosphorylase b?
What was added? Biproduct?
Phosphorylase a phosphatase (PP1)
2 H2O molecules.
Biproduct 2 pi
169
What are the active and inactive forms of the Glycogen synthase enzyme?
Active: glycogen synthase a
Inactive: glycogen synthase b
170
Is the active form (glycogen synthase a) phosphorilated or de-phosphorilated? On what residues?
Dephosphorilated on the 3 serine residues
171
What must happen in order to glycogen synthase to become phosphorylated (inactive)?
CKII needs to phosphorylate GSK3 to activate it, then GSK3 phosphorylates glycogen synthase
172
What inhibits GSK3 and activates PP1?
Inuline
173
What inhibits PP1? Activates?
Inhibit: Glucagon, epinephrine
Activate: Insulin, G6P, Glucose
174
Look at slide 47, 48, 49. Discuss once mastered all card!!! :)
Talk about it out loud with someone
175
How are each of the 8 glucose residues linked?
alpha(1-->4) glycosidic linkages.
176
What is the function of the glucosyltransferase activity in the formation of the 8-glucolse long primer?
Brings glucosyl group (new glycogen molecule) to UDP-glucose
177
What is the function of glycogen synthase?
How many residues does the activity of glycogen synthase require?
Catalyzes the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branched glycogen molecule.
At least 4!
