Intermediary metabolism Flashcards
(86 cards)
1
Q
What do aspirin, viagra and penicillin have in common?
A
They are enzyme inhibitors
2
Q
What does an enzyme affect during a reaction?
A
The transition state
Less activation energy needed to reach transition state
3
Q
Which 2 parameters characterize enzymes?
A
- Vmax
- Km
4
Q
Does hexokinase or glucokinase have a higher Vmax?
A
Glucokinase
So, hexokinase is saturated faster
5
Q
Does hexokinase of glucokinase have a higher Km?
A
Glucokinase
Glucokinase acts as a sensor
6
Q
In which type of cells is hexokinase found in?
A
All other body cells
7
Q
Which type of cells is glucokinase found in?
A
- Hepatocytes
- Pancreatic B cells
8
Q
How is competitive inhibition reversible?
A
Increase the substrate
9
Q
What enzyme parameter is changed by competitive inhibitors?
A
Km
More time needed to reach Vmax
10
Q
Which enzyme parameter is changed by non-competitive inhibitors?
A
Vmax
Lower
11
Q
What is allosteric regulation?
A
Shifting the equilibrium between active and inactive enzyme conformations.
Inhibitor shifts equilibirum to the right. Activator shifts equilibrium
12
Q
How is glycogen phosphorylase allosterically acivated?
A
- AMP binds outside of the active site
- Phosphorylase kinase attaches phosphates outside of the active site
Phosphorylation can either activate or deactivate an enzyme, mostly acti
13
Q
How are enzymes regulated?
A
- Competitive inhibition
- Allosteric regulation
- Hormonal regulation (via phosphorylation)
- Gene transcription
14
Q
What regulation of enzymes does glucagon activate?
A
Phosphorylation by activating protein kinase A by cAMP second messenger
15
Q
How does insulin regulate phosphorylation?
A
Insulin inhibits the activation of protein kinase A
16
Q
How does active protein kinase A increase gluconeogenesis?
A
- Protein kinase A activates phosphorylase kinase
- Phosphorylase kinase activates glycogen phosphorylase
- Protein kinase A phosphorylates glycogen synthase (deactivation)
These enzymes are activated by phosphorylation
17
Q
Do muscles respond to glucagon or epinephrine?
A
Epinephrine
18
Q
How does epinephrine regulate glycogen phosphorylase?
A
- Epinephrine stimulates Ca+ release from the ER
- Ca+ stimulates protein kinase C
- Ca+-calmodulin activates calmodulin dependent protein kinase and phosphorylase kinase
- Protein kinase C, calmodulin dependent kinase and phosphorylase kinase inactivate glycogen synthase
- Phosphorylase kinaseactivates glycogen phosphorylase
19
Q
What happens when there is a prolonged need for an enzyme?
A
Increased gene transcription
20
Q
At which two levels is human metabolism controlled?
A
- Intracellular metabolites
- Hormones and neuronal signals
21
Q
To which three substances can glucose-6-phosphate convert to?
A
- Glycogen via glucose-1-phosphate
- Pyruvate via fructose-6-phosphate
- Ribose-5-phosphate via 6-phosphate gluconate
22
Q
To which substances can pyruvate be converted to?
A
- Alanine
- Lactate
- Oxaloacetate
- Glucose-6-phosphate via oxaloacetate
- Acetyl CoA
Conversion t Acetyl CoA is decisive step!!
23
Q
To which substances can Acetyl CoA be converted to?
A
- Fatty acids
- CO2
- Cholesterol via 3-hydroxy-3-methyl-glutaryl CoA
- Ketone bodies via 3-hydroxy-3-methyl-glutaryl CoA
24
Q
What are the three main fates of glucose?
A
- Glycogen via glucose-1-phosphate
- Pentose phosphate pathway via ribose-5-phosphate
- Pyruvate via Fructose-6-phosphate
25
UDP-glucose from glucose-1-phosphate has which fates?
* Glycogen
* Lactose via UDP-galactose
* Glucuronides via UDP-glucuronate
* Glycoproteins, glycolipids and proteoglycans via UDP galactose and UDP glucuronate
| glucuronides make susbstances water soluble
26
Function of NADPH produced from the PPP?
* Biosynthesis
* Prevention of oxidative damage
27
How is glycolysis inhibited?
* Glucose-6-phosphate inhibits hexokinase
* ATP
* Citrate inhibits phosphofructokinase
* Acetyl CoA inhibits pyruvate dehydrogenase
| citrate is first metabolite in citric acid cycle
28
How is glycolysis supported?
* AMP
* Fructose-2,6-biphosphate activates phosphofructokinase
* Fructose-1,6-biphosphate activates pyruvate kinase
29
When glycogenolysis starts, how long during fasting does this occur?
| Glycogenolysis is breakdown of glycogen to produce glucose and energy
About 24 h
| Until glycogen storage is depleted
30
Role of fructose-2,6-phosphate on glycolysis pathway?
It activates phosphatefructokinase 1, activating glycolysis and inhbiting gluconeogenesis
31
Which hormone controls the speed of gluconeogenesis?
Glucagon
32
Which enzyme does glucagon regulate to initiate gluconeogenesis?
Pyruvate kinase is activated (dephosphorylation)
33
Pyruvate is not converted to acetyl CoA but to what substance during gluconeogenesis?
Oxaloacetate under activation of pyruvate carboxylase by acetyl CoA itself
34
How is glucose made from pyruvate during gluconeogenesis?
1. From pyruvate to oxaloacetate via glucose carboxylase
2. From oxaloacetate to phosphoenolpyruvate
3. To glyceraldehyde-3-phosphate
4. To fructose-1,6-biphosphate
5. To Fructose-6-phosphate by Fructose-1,6-biphosphatase
6. To glucose-6-phosphate
7. To glucose by glucose-6-phosphatase
| Gluconeogenesis only in the liver
35
How much of all glucose enters the PPP?
30%
36
Which compound is produced that also stimulates fatty acid synthesis for example?
2 NADPH from 2 NADP+
| Only produced via oxidative pathway
37
Via which metabolite is ribose-5-phosphate produced if the pathway is oxidative?
Glucose-6-phosphate
38
Via which metabolite is ribose-5-phosphate porduced if the pathways is non-oxidative?
Fructose-6-phosphate
39
What is a nucleoside
A 5 carbon molecule, usually a ribose molecule with a nitrigenous base
40
From which substance are nucleotides made of?
Ribose-5-phosphate
41
What is the difference between nucleosides and nucelotides?
Nucleotides are nucleosides with 1,2 or 3 phosphate groups attached
42
Which nucleosides make up nucleotides in DNA?
* Adenine
* Guanine
* Cytosine
* Thymine
43
Which nucleosides are purines?
* Adenine
* Guanine
44
Which nucleosines are pyrimidines?
* Thymine
* Cytosine
45
Which enzyme facilitates the conversion of ribose-5-phosphate to 5-phosphoribosyl 1-pyrophosphate (PRPP)
PRPP synthetase
46
Which activated molecule supports nucleotide production?
5-phosphorybosyl 1-pyrophosphate (PRPP)
47
Which molecules are needed to go from an amino acid to uridine monophosphate (UMP) during pyrimidine synthesis?
* Carbamoyl phosphate
* PRPP
* Ribose-5-phosphate
48
How is carbomoyl phosphate produced in pyrimidine synthesis?
Glutamine+CO2+2ATP
49
What is uridinyl monophosphate (UMP)?
An intermediate in pyrimidine synthesis
50
What is the difference between purine and pyrimidine synthesis?
* PRPP is still formed, however:
* PRPP and glutamine together form IMP as an intermediate
* A lot of ATP (6) is used for 11 steps
51
Which enzyme facilitates the formation of dNDP's from NDP?
Ribonucleotide reductase
| It removes an alcohol group and adds an H+ instead
52
Which molecule that is produced during the oxidative PPP is used during production of dNDP's?
NADPH
| So, if there is alot of NADPH, nucleotide synthesis is activated
53
For which disease was 5-Fluorouracil (5-FU) used?
Cancer, to block DNA synthesis
54
How does 5-FU inhibit DNA synthesis?
5-FU is an analogue of uracil or thymine, but with a fluor group added where binding between nucleotides is supposed to occur. As a result no basepairing and DNA synthesis stops.
55
Which amino acids are needed during pyrimidine synthesis?
* Glutamine to produce carbamoyl phosphate
* Aspartate
56
What does pyruvate dehydrogenase do?
Metabolizes pyruvate into acetyl CoA
| PDH is therefore an important factor to regulate to determine glucose fa
57
Can acetyl CoA be used to synthesise glucose?
No
58
When is fat produced?
When insulin is produced and glycogen storage is full
59
Which enzyme activated PDC?
Phosphatase stimulated by insulin
| Ca+ also activates the enzyme
60
Which enzyme deactivates PDC?
Kinase which adds a phosphate
61
Which other factors regulate the deactivation of PDC by kinase?
* ADP inhibits inactivation (If alot is formed during PDC inactivation)
* Pyruvate inhibits inactivation (If there is alot of pyruvate)
* Acetyl CoA activates kinase (To stop xtra CoA forming)
* NADH activates kinase (To stop xtra NADH forming)
62
Which substances regulate TCA cycle?
* Citrate inhibits citrate synthase
* NADH inhibits more formation of NADH
* ADP activates TCA cycle as ADP can be used to generate ATP in the electron transport system
* Ca+ activates cycle by insulin
63
When is fatty acid synthesis a fully comitted step?
If malonyl-CoA is produced from acetyl-CoA by acetyl-CoA carboxylase
64
How is acetyl-CoA carboxylase regulated?
* At hormonal level by insulin and glucagon
* At cellular level by citrate and AMP
65
When is acetyl carboxylase activated?
* When citrate binds to inactive carboxylase
* When insulin activates protein phosphatase to remove the phosphate group
66
When is acetyl CoA inactivated?
* When glucagon activates protein kinase to bind a phosphate group
* When there is a surplus of AMP, protein kinase is inactivated
67
How do beta-oxidation and fatty acid synthesis never occur simultaneously?
Malonyl-CoA inhibtis FA CoA from entering the mitochondria
68
By which two metabolites is fatty acid metabolism regulated?
* Citrate activates acetyl CoA carboxylase
* Palmitoyl CoA inhibits acetyl CoA carboxylase
69
What funtion does glucose have for adipose cells?
Glycerol is made from glucose to make triglycerides
70
Which enzyme is stimulated by insulin in order to facilitate fatty acids entering adipose cells?
Lipoprotein lipase
71
Which GLUT transporter is insulin dependent?
GLUT4
72
Glucagon does what to PDC?
It deactivates it in order to convert pyruvate onto oxaloacetate
73
From which metabolite does gluconeogenesis start?
Oxaloacetate
74
Which are mobilized first: fatty acids or amino acids?
Amino acids
| This is seen by the increase of nitrogenous products in urine
75
What effect does glucagon have on adipose cells?
* Glucagon activates cAMP
* cAMP activates protein kinase A
* Protein kinase A activates adipocyte triglyceride lipase
* Fatty acids and glycerol transported into the blood
76
Four fates of acetyl CoA are?
* TCA cycle
* Fatty acid synthesis
* Ketone bodies
77
During fasting, which compound is used for glucose production?
Glycerol from adipose tissue
78
During fasting, fatty acids are used to produce what to generate energy in the muscle?
Acetyl CoA
79
During fasting fatty acids transported to the liver are used to make what compound that can be used by the brain and muscles?
Ketone bodies
80
During fasting, ketone bodies are converted into what in the muscle to generate energy?
Acetyl CoA
81
Describe ketone body production in short
1. Two acetyl CoA molecules produce acetoacetate
2. Acetoacetate can be spontaneously converted to acetone, releasing CO2
3. Acetoacetate can be converted to beta-hydroxybutyrate bybeta-hydorxybutyrate dehydrogenase
82
Describe ketone body to acetyl CoA in short
1. Beta-hydroxybutyrate into acetoacetate
2. Acetoacetate into acetoacetyl CoA
3. Acetoacetyl CoA into two molecules of acetyl CoA
83
During starvation which tissue uses glucose alot
nervous system
84
During starvation, which tissues use fatty acid as fuel?
* Skeletal muscle
* Heart muscle
* Liver
* Kidney a bit
85
Which tissues use ketone bodies during starvation?
* Nervous system
* Skeletal muscle
* Heart muscle
* Intestinal epithelial cells
* Kidney a bit
| Liver does NOT use ketone bodies
86
How does epinephrine influence glucose mobilization?
Glucose is produced from triglycerides, pyruvate and lactate (muscle) and glycogen to increase blood glucose levels
