Lecture 17 Flashcards

1
Q

What is gluconeogenesis?

A
    • indirect synthesis of glucose

- - not exactly the reverse of glycolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which of the following is NOT a reason as to why our bodies spend energy to make glucose?
A) we can only store 190g of glucose at any time
B) stores of glucose only last for little over a day.
C) we need to make sure enough glucose is present for the brain
D) We don’t actually make glucose and its all a hoax

A

D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

True or false.

The organs that are capable of gluconeogenesis are the liver and the kidney

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

True or false

non-carbohydrate precursors that can enter gluconeogenesis include glycerol, amino acids, and lactate

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

T or F, major tissue for gluconeogenesis is the LIVER and occurs mainly in cytosol, though some precursors come from the mitochondria

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why isn’t glucose synthesis simply the reverse of glucose metabolism?

A

– Energetics

– also there are 3 key reactions in glycolysis are energetically very favorable – i.e. deltaG is negative:

glucose –> glucose 6-P

fructose 6-P –> fructose 1,6-BP

PEP –> pyruvate

– this means the reactions are, essentially, irreversible and thus evolution needed a way around this to synthesize glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the different enzymes involved in gluconeogenesis?

A
    • pyruvate carboxylase, – phosphophenol –pyruvate carboxykinase
    • fructose 1 6 bisphosphatase and

– glucose 6 phosphatase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where does gluconeogesis occur?

A

– cytosol except for the initial step that occurs in the matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which enzyme is involved in the conversion of pyruvate to oxaloacetate?

A

– pyruvate carboxylase

– carboxylation of pyruvate occurs in mitochondria – oxaloacetate must then be sent to the cytoplasm for conversion to PEP

– occurs through a malate intermedediate and uses a malate transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the net input/output during the formation of oxaloacetate from pyruvate?

A

will input 1ATP, 1 HCO3 (bicarbonate). will release and ADP and Pi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which cofactor is necessary for the first reaction of gluconeogesis?

A

biotin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

True or false

There is a transfer of NADH from inside the matrix to outside the matrix during gluconeogenesis

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which enzyme is involved in the use and reformation of NADH/NAD+ during the first step of gluconeogesis

A

malate dehydrogenase

– because remember oxaloacetate is converted to malate intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

True or false

Lactate can be used as precursor to pyruvate and amino acids can be formed into oxaloacetate

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which enzyme is responsible for the formation of phosphophenol pyruvate (PEP) from oxaloacetate

A

PEP carboxykinase

– a decarboxylation and phosphorylation reaction converts oxaloacetate to PEP while burning a GTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the next in/output of conversion of oxaloacetate to PEP?

A

– 1 GTP input and an output of one GDP and CO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

True or false
a carboxylation followed by a decarboxylation is a coupling event that occurs in gluconeogenesis in order to overcome the positive free energy of converting to PEP

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is gluconeogenesis different from glycolysis?

A
    • energetics
    • deltaGknot prime for reverse glycolysis = + 31 kJ/mol – Not going to happen

– gluconeogenesis uses a carboxylation/decarboxylation cycle to get PEP from pyruvate, and this is much more energetically favorable deltaG = -25 kJ/mol

– however, it has to utilize an ATP and a GTP, energetically expensive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

T or F, after formation of PEP, gluconeogenesis proceeds as reverse glycolysis

A

True; reaction direction is determined by the concentrations of reactants, until we hit the fructose 1,6-BP step

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the net output/input between PEP to FBP?

A

-1ATP -1NADH -1H20 and + 1 ADP + 1Pi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Which enzyme is responsible for the conversion of FBP to F6P

A

– FBPase –> allosteric enzyme under

– Fructose 1,6 - BP is converted to fructose 6-P by dephosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the products of the reaction of FPasE?

A

– one Pi

23
Q

What enzyme is responsible for the formation of glucose from G6p?

A

– glucose 6-phosphatase

– Fructose 6-P readily converts to glucose 6-P

– this enzyme allows liver and kidney want to send glucose into the bloodstream

– this enzyme is also expressed primarily in those tissues

24
Q

true or false GPase is present only in the liver and kidney

A

true

25
Q

true or false

FPase is an allosteric enzyme

A

true

26
Q

What is the next product of gluconeogenesis when 2 pyruvate are used?

A
    • 1 glucose
    • 4ADP
    • 2GDP
    • 6Pi
    • 2NAD+
    • 2H+
27
Q

How many NTPS are burned per glucose regenerated from pyruvate?

A
    • 6
    • 4ATP
    • 2GTP
28
Q

T or F, lactate can serve as a precursor for gluconeogenesis via the Cori Cycle

A

True

29
Q

T or F, under heavy exertion, lactate produced by muscles isn’t wasted, as it can be regenerated into glucose by the liver

A

True

30
Q

Which two amino acids are mainly involved in the gluconeogenic pathway?

A

– Alanine and Glutamine

31
Q

When would amino acid metabolism occur?

A

– when fasting or starving, muscle protein will breakdown

– main source of pyruvate

32
Q

What are major control mechanisms?

A

– substrate-level control, concentration of reactants or products of the reaction activating/inhibiting the reaction

– feedback control, products of Citric Acid Cycle influencing enzymatic reactions.

At high ATP concentrations, flux through Citric Acid cycle slows and intermediates accumulate

33
Q

Describe phosphofructokinase regulation

A

– PFK an allosteric enzyme that is activated (R state) by low energy charge (low ATP) and inhibited by high energy

– ATP is also a substrate for the reaction, so binds in the active site

– it binds at the allosteric site with lower affinity so only inhibits at HIGH ATP concentrations

34
Q

True or false

PFK is a homotetramer

A

true

35
Q

What are the pathways that F6P can take in the context of glucose breakdown?

A

it can turn into F16BP or turn into F26BP

36
Q

True or false

The non phosphorylated PFK2 enzyme stimulates glycolysis

A

True

– regulation by phosphorylation, activating one activity versus the other

– kinase activity versus phosphatase activity is controlled by hormone regulation in liver

37
Q

How does the conformation of PFK change when phosphorylated vs not?

A

– when phosphorylated the FBpase site is connected and the kinase site is separated, resulting in breakdown of fructose 26 bisphosphate.

– When not, the kinase site is together and the phosphatase site is not, resulting in increase kinase activity and formation of F26BP

38
Q

True or false

insulin stimulates FBP2 by increasing protein phosphatase activity

A

True

39
Q

True or false

glucagon exerts its influence on F2BP levels by increasing activity of cAMP-dependent protein kinase

A

True

40
Q

True or false

pyruvate kinase is allosterically activated by F16BP

A

true

41
Q

Which of the following is pyruvate kinase not inhibited by?
A) acetyl coa
B) ATP/alanine
C) F16BP
D) cAmp dependent phosphorylation in the liver

A

C

42
Q

true or false

PC and PEPCK are activated by acetyl goa

A

true

43
Q

True or false

glucagon stimulates PEPCK and insulin inhibits it

A

true

44
Q

true or false

hexokinase is inhibited by G6P in non-liver cells

A

true; however liver isozyme (hexokinase IV/glucokinase) is NOT subject to feedback inhibition

45
Q
Which of the following stimulate PFK activity?
A) Citrate
B) ATP
C) AMP/ADP
D) G6P
A

C; AMP, ADP and also F2, 6 BP

46
Q

True or false

citrate and ATP stimulate FBPASE

A

false. inhibit pfk

47
Q

true or false

FBpase is inhibited by F26P and amp

A

true

48
Q

true or false

the reactions between G69 and glucose and vice versa are regulated by substrate level control except in the liver

A

true

49
Q

Describe the regulation of Hexokinase

A

– inhibited by product G-6-P; however, the liver isozyme (hexokinase IV/glucokinase) is NOT subject to feedback inhibition

50
Q

Explain how insulin and glucagon activate glycolysis and gluconeogenesis.

A

– insulin activates kinase activity (high glucose, F2, 6B activates Glycolysis inhibits gluconeogenesis)

– glucagon activates phosphatase activity (low glucose, no activation of Glycoloysis)

51
Q

T or F, pyruvate kinase is allosterically inhibited by: Acetyl- CoA

A

True, also ATP, amino acids and hormonal regulation in liver isoforms

52
Q

T or F, PC and PEPCK are activated by Acetyl-CoA

A

True

53
Q

T or F, glucagon tells us about low blood sugar

A

True, this activates the synthesis of phosphoenol-pyruvate carboxykinase