Glucose Metabolism Flashcards
(114 cards)
1
Q
What are the main functions of glucose as a fuel?
A
- Extracellular matrix and cell wall polysaccharides
- Storage as glycogen, starch, and sucrose
- Oxidized to Pyruvate via Glycolysis
- Oxidized to Ribose-5-phosphate via the Pentose Phosphate Pathway
2
Q
What is glycolysis?
A
Glucose is degraded to yield pyruvate, which yields some energy
3
Q
What is gluconeogenesis?
A
Glucose is formed from a non-carbohydrate source; mainly proteins
4
Q
What is glycogenesis?
A
Glycogen is polymerized from glucose units
5
Q
What is glycogenolysis?
A
Glycogen is degraded to glucose units
6
Q
What is glycolysis also called? Why?
A
- EMP Pathway
- Because of the scientists: Euler-Meyerhof-Parnas
7
Q
What was particular about the scientists Euler-Meyerhof-Parnas?
A
They were all Jewish scientists that practiced during the World Wars
8
Q
In which mechanisms is DHAP located? (2) What can it become? Through what enzyme?
A
1) Glycolysis
- Triose phosphate isomerase
- Glyceraldehyde-3-phosphate
2) Fatty acid synthesis
- Glycerol-3-phosphate dehydrogenase
- Glycerol-3-phosphate
9
Q
What does GAPDH stand for?
A
Glyceraldehyde-3-phosphate dehydrogenase
10
Q
What does PEP stand for?
A
Phosphoenolpyruvate
11
Q
Where does substrate-level phosphorylation occur in glycolysis?
A
- Pyruvate kinase
- Phosphoglycerate kinase
12
Q
Where does tautomerization occur in glycolysis? What is it?
A
- Conversion of the double bond by exchanging electrons
- Pyruvate kinase
13
Q
In glycolysis, why can phosphorylation only occur on C-6 in hexokinase?
A
Because C-1 is a carbonyl group and cannot be phosphorylated
14
Q
What does phosphohexoisomerase do?
A
- Converts Glucose-6-phosphate to Fructose-6-phosphate
- Moves the double bond to C-2 so that C-1 can be phosphorylated and become Fructose-1,6-bisphosphate
15
Q
How many carbons do DHAP and glyceraldehyde-3-phosphate contain?
A
3 carbons each
16
Q
What is used in glycolysis?
A
- 1 Glucose
- 2 ATP
- 2 NAD+
- 4 ADP
17
Q
What is made in glycolysis?
A
- 2 Pyruvate
- 4 ATP (but 2 net)
- 2 NADH
18
Q
What must be done for glycolysis to continue?
A
NADH must be oxidized to NAD+ by fermentation
19
Q
What can pyruvate generate under anaerobic conditions? (2)
A
1) Fermentation to 2 Ethanol and 2 CO2 in yeast
2) Fermentation to 2 Lactate
20
Q
How is NAD+ generated in glycolysis?
A
By converting pyruvate to lactate through lactate dehydrogenase
21
Q
What particular type of cells are capable of converting pyruvate to lactate? Why?
A
- Erythrocytes since they do not have a mitochondria
- They need NAD+ to continue glycolysis
22
Q
Where is lactate converted to glucose?
A
In the liver
23
Q
What does the Cori Cycle explain?
A
How glucose is metabolized in muscles and how lactate is generated
24
Q
What are possible glucose sources that can enter glycolysis?
A
- Glucose
- Lactose
- Sucrose
- They can enter at various points
25
What happens in glycogenolysis? What enzyme is required? What does it yield?
- Glycogen phosphorylase
- Glucose is made from glycogen
- Glycogen is cleaved at its NON-reducing end
- Yields glucose-1-phosphate
26
Which tissues depend mainly on glucose?
Brain, RBC, testes, renal medulla, embryo
27
What causes pregnancy-induced insulin resistance?
The embryo depends heavily on glucose
28
What compounds are converted to what in gluconeogenesis?
- Formation of glucose from non-carbohydrate sources (pyruvate, glycerol, glucogenic AA)
29
What is the main site of gluconeogenesis? What are other sites?
- Main: Liver
| - Also, renal cortex and intestinal epithelium
30
Recovery after vigorous exercise involves ________________
gluconeogenesis
31
Which four enzymes are different in gluconeogenesis? Why?
- To bypass non-reversible reactions in glycolysis
- Pyruvate carboxylase and PEP carboxykinase
- Fructose-1,6-biphosphoatase-1
- Glucose-6-phosphatase
32
Which enzyme in glycolysis do pyruvate carboxylase and PEP carboxykinase replace in gluconeogenesis?
Pyruvate kinase
33
Which enzyme in glycolysis does fructose-1,6-biphosphoatase-1 replace in gluconeogenesis?
Phosphofructokinase-1
34
Which enzyme in glycolysis does glucose-6-phosphatase replace in gluconeogenesis?
Hexokinase
35
Which enzyme does pyruvate carboxylase resemble?
ACC since it contains biotin and uses ATP
36
What are the two steps to convert phosphoenolpyruvate from pyruvate?
1) Pyruvate + Bicarbonate --> Oxaloacetate
| 2) Oxaloacetate --> Phosphoenolpyruvate
37
What enzyme is used to convert: Pyruvate + Bicarbonate --> Oxaloacetate? Where does it occur? What energy source does it use?
- Pyruvate carboxylase
- Mitochondria
- Uses ATP
38
What enzyme is used to convert: Oxaloacetate --> Phosphoenolpyruvate? Where does it occur? What energy source does it use?
- PEP carboxykinase
- Cytosol/Mitochondria
- Uses GTP
39
All the intermediates of __________ can enter gluconeogenesis
Intermediates of TCA
40
Different AA yield different products in gluconeogenesis. What kind of products?
Pyruvate, a-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate
41
Which AA are not glucogenic?
Leucine and Lysine
42
What are the two fates of Glucose-6-Phosphate?
- Glycolysis
| - Pentose Phosphate Pathway
43
What is the Pentose Phosphate Pathway also called?
Hexose monophosphate pathway
44
What is the Pentose Phosphate Pathway more common in?
- Highly proliferative cells (ex: skin)
- Cells of FA biosynthesis
- Cells of sterol synthesis
- Cells with oxidative stress (RBCs)
45
G6P leads to intermediates in two ways in the Pentose Phosphate Pathway. What are they?
1) Oxidative phase:
- G6P --> Ribulose-5-phosphate
2) Non-oxidative phase:
- Ribulose-5-phosphate --> G6P
46
What is the most important enzyme of the Pentose Phosphate Pathway?
G6P dehydrogenase
47
What enzyme converts ribulose-5-phosphate to ribose-5-phosphate?
Phospho-pentose isomerase
48
What can ribose-5-phosphate become? What is its use?
- Nucleotides, coenzymes, DNA, RNA
| - Proliferation and gene expression
49
Where does NADPH come from?
From the Pentose Phosphate Pathway
50
What are the functions of NADPH?
* FA synthesis in liver, kidney, and lactating mammary gland
* Cholesterol/steroid synthesis in liver, adrenal and gonads
* Alleviation of oxidative stress
51
What happens if hydrogen peroxide is not metabolized properly?
- It yields a hydroxyl free radical
| - Dangerous for lipids, proteins, and DNA
52
How does NADPH alleviate oxidative stress?
- NADPH is converted to NADP+ through glutathione reductase
- Donates electrons and reduces GSSG to GSH
- GSH has two hydrogens, which can be donated to hydrogen peroxide to turn them into water
53
What is GSH? What is GSSG?
o GSH: reduced form of glutathione
| o GSSG: oxidized form of glutathione
54
What is the function of the Non-Oxidative Phase of the Pentose Phosphate Pathway? When is it used?
* Regenerates G-6-P from R-5-P
| * Used in tissues requiring more NADPH than R-5-P
55
What regulates the Pentose Phosphate Pathway?
Intermediates, such as NADPH
56
What does NADP+ do in terms of regulation of the pentose phosphate pathway? What does NADPH do in terms of regulation?
- NADP+ activates G6PD and the PPP
| - NADPH inhibits G6PD and the PPP (negative feedback - glycolysis will predominate)
57
Why is glycolysis regulated?
To maintain constant ATP levels
58
Which three enzymes are regulated in glycolysis?
- Hexokinase
- PFK-1
- Pyruvate kinase
59
Which compounds regulate expression/function of glycolytic enzymes?
Glucagon, epinephrine, and insulin
60
How many isoforms does hexokinase have?
I to IV
61
What are isozymes?
Slight differences in AA sequences, which creates slight changes in their function
62
Hexokinase 4 is also called what?
Glucokinase
63
Hexokinase I and II are predominantly expressed where? What do they have a high affinity for?
- Muscle
| - High affinity for glucose
64
As the glucose concentration increases, how does the activity of Hexokinase I and II change? What about Hexokinase IV?
I and II: increases dramatically
| IV: does not increase as much, lower affinity for glucose
65
What are Hexokinase I and II allosterically inhibited by?
Glucose-6-phosphate, end-product of the reaction
66
Where is Hexokinase IV predominantly expressed? How is their affinity for glucose?
- Liver
| - Low affinity for glucose
67
Why is the low affinity for glucose of Hexokinase IV idea?
Since it is expressed in the liver, which does not used glucose (sends it to other body parts)
68
Is Hexokinase IV inhibited by glucose-6-phosphate? What about Hexokinase I and II?
I and II: Yes
| IV: No
69
In the _____, glucose escapes glycolysis through a specific regulatory protein called _____
liver
| GKRP
70
How does glucose escape glycolysis in the liver at low concentrations?
GKRP binds to Hexokinase IV and translocates it into the nucleus, which is not a site of glycolysis
71
When glucose concentration is low, ________ promotes the association between GKRP and hexokinase IV, which is shuttled to the nucleus
fructose-6-phosphate
72
What are the three major sites of glycolysis and gluconeogenesis?
Liver, kidney, and epithelial cells
73
When is hexokinase IV utilized to generate energy through glycolysis?
When there is high blood glucose
74
In gluconeogenesis, what enzyme replaces hexokinase from glycolysis?
glucose-6-phosphatase
75
In gluconeogenesis, what enzyme replaces PFK-1 from glycolysis?
fructose 1,6-bisphosphatase-1 (FBPase-1)
76
In gluconeogenesis, what enzyme(s) replaces pyruvate kinase?
- Pyruvate carboxylase
| - PEP carboxykinase
77
PFK-1 commits _____ to ______
glucose
| glycolysis
78
What inhibits PFK-1?
- High ATP
| - High citrate, which increases ATP-inhibition
79
What stimulates PFK-1?
- High ADP
| - High AMP
80
What inhibits FBPase-1?
High AMP
81
What pathways does insulin promote?
- Glycolysis
- Glycogenesis
- TG synthesis
82
What pathway does glucagon inhibit? What does it stimulate?
- Inhibits glycolysis
| - Stimulates gluconeogenesis
83
Is Fructose-2,6-bisphosphate used in glycolysis?
NO, it is just a regulator of the glycolytic pathway
84
What does F26BP activate? What does it inhibit?
- Activates PFK-1 (glycolysis)
| - Inhibits FBPase-1 (gluconeogenesis)
85
Fructose 2,6-bisphosphate is synthesized from ________ by _____, which requires ____
Fructose 6-phosphate
PFK-2
ATP
86
Fructose 6-phosphate is synthesized from ___________ by __________, which does not require _____
Fructose 2,6-bisphophate
FBPase-2
ATP
87
Are PFK-1 and FBPase-1 located on the same protein?
No
88
Are PFK-2 and FBPase-2 located on the same protein?
Yes
89
FBPase-2 is activated when PFK-2 is (phosphorylated/dephosphorylated)
phosphorylated
90
What stimulates the phosphorylation of PFK-2?
Glucagon
91
An increase of FBPase-2 stimulates what?
Gluconeogenesis
92
Insulin causes (phosphorylation/dephosphorylation) of PFK-2 by stimulation what?
dephosphorylation
| phosphoprotein phosphatase
93
An increase of PFK-2 stimulates what?
Glycolysis
94
Xylulose-5-phosphate is found where?
In the non-oxidative phase of the pentose phosphate pathway
95
What is the role of xylulose-5-phosphate? What does it stimulate/inhibit?
- Brings back glucose-6-phosphate to recycle glucose
- Stimulates glycolysis
- Inhibits gluconeogenesis
96
High amounts of Xylulose-5-phosphate are acquired when there are high amounts of ______
glucose
97
What inhibits pyruvate kinase?
- Pyruvate
- ATP
- Acetyl-CoA
- Long-chain fatty acids
98
What activates pyruvate kinase?
Fructose 1,6-bisphosphate
99
How is pyruvate kinase inactivated? Where does this occur?
- When it is phosphorylated
- ONLY occurs in the liver (muscle is not affected by PKA)
- PKA phosphorylates it
100
Pyruvate in the liver can undergo _________ to yield glucose, or _________ to yield energy
gluconeogenesis
| TCA cycle
101
How can pyruvate in the liver go through gluconeogenesis?
Converted to oxaloacetate by pyruvate carboxylase
102
How can pyruvate in the liver go through the TCA cycle?
Converted to Acetyl-CoA by the pyruvate dehydrogenase complex
103
What does high Acetyl-CoA concentration activate and inhibit?
- Activates pyruvate carboxylase
| - Inhibits the pyruvate dehydrogenase complex
104
How does a high amount of glucose contribute to an increase in FA synthesis?
- Glucose in PPP produces X-5-P
- X-5-P activates a phosphatase, which dephosphorylates ChREBP, which moves to the nucleus
- The dephosphorylation of ChREBP in the nucleus makes it mix with MLS
- Once the mixture binds to ChoRE, they promote mRNA synthesis for a specific gene, such as Pyruvate kinase, Acetyl-CoA carboxylase, FA synthase
105
How is FOXO1 inactivated? What happens?
- Inactivated when it is phosphorylated
| - Forces it to remain in the cytoplasm, degradation through ubiquination
106
How is FOXO1 activated? What happens?
- Activated when it is dephosphorylated by phosphoprotein phosphatase
- Travels to the nucleus
107
In the nucleus, FOXO1 creates mRNA sequences for what? They are enzymes of what?
- PEP carboxykinase and glucose-6-phosphate
| - Enzymes of gluconeogenesis
108
FOXO1 suppresses the transcription of enzymes of which pathways?
Glycolysis, PPP, and FA synthesis
109
What is the consequence of the fast multiplication of cancerous cells?
Oxygen cannot be provided quickly enough (hypoxia)
110
In cancer cells, proteins are involved in which pathways?
Glycolysis and PPP
111
What are the transcription factors called in cells exposed to hypoxia?
HIFI: Hypoxia-Inducible Factor 1
112
What does HIFI activate? What does it inhibit?
- Activates the enzymes of glycolysis
| - Inhibits the enzymes that promote the synthesis of Acetyl-CoA
113
Why does HIFI inhibit Acetyl-CoA synthesis?
- Since the cells are exposed to hypoxia, they lack oxygen
| - Acetyl-CoA is the precursor for the TCA cycle, which requires oxygen
114
Why does HIFI promote the PPP?
Since precursors for DNA and RNA are from the PPP
