Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular bioscience > Gluconeogenesis and regulation > Flashcards

Gluconeogenesis and regulation Flashcards

1
Q

Define Gluconeogenesis

A

Lactate from anaerobic metabolism of pyruvate can be converted back to glucose in the liver and kidney

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

What are the precursors of Gluconeogenesis?

A

Non-carbohydrate sources also provide precursors for gluconeogenesis

Most amino acids

Glycerol (via DHAP)

Metabolites which can be converted to pyruvate or oxaloacetate

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

What happens to the precursors formed in non-gluconeogenic tissues?

A

Transported to the liver

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

What takes place in the liver for the Cori cycle?

A

In the liver: Fatty acids are converted into ATP and Co2 + H2O is released. ATP is converted to glucose by lactate

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

What takes place in the muscle for the Cori cycle?

A

Muscle: Glucose is transported into the muscle, converting to glycogen and then back to glucose before producing ATP and lactate. Lactate then transported back to the liver.

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

Bypassing the irreversible steps to glycolysis: How is Oxaloacetate formed from pyruvate?

A

Requires 2 enzymes and 2 high energy phosphates

Pyruvate binds with HCO3
ATP is converted to ADP+Pi
Oxaloacetate is then formed

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

Bypassing the irreversible steps to glycolysis:

How is Phosphoenol pyruvate formed from Oxaloacetate?

A

GTP is converted to GDP
CO2 is lost
Forming Phosphoenolpyruvate
Highly endergonic

The energy supplied by decarboxylation helps drive the reaction

Additional energy supplied by GTP hydrolysis

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

What enzyme catalysis the conversion of Pyruvate to Oxaloacetate?

A

Pyruvate Carboxylase

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

What enzyme catalysis the conversion of Oxaloacetate to Phosphoenolpyruvate?

A

PEP carboxykinase

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

Bypassing the irreversible steps to glycolysis:

How is Fructose-1,6-bisphosphate converted to Fructose-6-phosphate?

A

F-1,6-bisphate is hydrolysed and Pi is lost

Hydrolysis of fructose-1,6-bisphosphate ester is thermodynamically favourable

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

Bypassing the irreversible steps to glycolysis:

How is Glucose-6-phosphate converted to Glucose?

A

G-6-phate is hydrolysed and Pi is lost

Hydrolysis of G-6-phate is thermodynamically favourable

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

Define Glucose-6-phosphatase

A

Membrane-bound enzyme localised on the smooth endoplasmic reticulum

Only present in liver and kidney

Has a high Km for Glucose-6-phosphate

Only active when substrate levels are high (substrate-level control)

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

Why is Gluconeogenesis regulated?

A

Meet major needs in the body:
1) ATP production

2) Production of precursors for other metabolic pathways

3) Conversion of pyruvate to glucose:
- To maintain blood [glucose] when alternative sources are exhausted
- Flux of metabolites through pathways must be tightly regulated
- Response to both intracellular and extracellular conditions

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

what 3 points are the pathways regulated?

A

1) Phosphorylation of glucose
2) Phosphorylation of fructose-6-phosphate
3) formation of pyruvate and ATP

All three steps are essentially irreversible under cellular conditions

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

What 3 different types of regulation controls enzyme activity?

A

Allosteric regulation: By substrate, products or effects (activators/inhibitors)

Covalent modification (phosphorylation)

Transcriptional activation

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

Regulation of Hexokinase: Whats the role of Hexokinase?

A

Effectively commits glucose to a fate within the cell

Glucose-6-phosphate can have a number of cellular fates

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

What inhibits hexokinase and how?

A

Glucose-6-phosphate is an allosteric inhibitor of hexokinase

Glucose-6-phosphate accumulates when all glucose-requiring pathways within the cell are full

Inhibits further glucose phosphorylation

18
Q

How does the regulation of Glucokinase differ from Hexokinase?

A

Important because of its role in glucose homeostasis

Predominant isoform present in the liver

Glucokinase has a higher Km for glucose

Affinity is approximately 50-fold lower than hexokinase

The liver only takes up glucose when blood [glucose] is high

19
Q

What regulates Glucokinase activity?

A

Fructose phosphates

20
Q

Glucokinase is inhibited by?

A

Fructose-6-phosphate: Glucose-6-phosphate (a precursor of glycogenesis) does not inhibit.

21
Q

What inhibits glucokinase?

A

Glucokinase regulatory protein:

GRP is present in liver cells

Binds to GK in the presence of fructose-6-phosphate

Glucose flux via glucokinase in the liver is usually low as a result

22
Q

Why does Fructose-1-phosphate compete for bind sites on GRP?

A

Only present after a carbohydrate-rich meal

Fructose-1-phosphate relieves inhibitory effect of GRP on glucokinase

Liver, therefore, acts as a major control point in maintaining blood glucose levels

Beta-islet cells in the pancreas also contain glucokinase and GRP

23
Q

Explain the regulation of glucose-6-phosphatase

A

High Km (substrate-level regulation)

The enzyme is only active when levels of glucose-6-phosphate

Levels only rise when all other pathways requiring glucose-6-phosphate are full

24
Q

Formation of fructose-1,6-bisphosphate represents?

A

Regulation of phosphofructokinase-1 which is a committed step in glycolysis

25
Q

What allosteric effectors does PFK-1 have?

A

ATP and Citrate
ADP
AMP

26
Q

allosteric effectors of PFK-1: What do ATP and Citrate do?

A

Signal a high energy state within the cell

ATP is a potent inhibitor of PFK-1 (decreases affinity for fructose-6-phosphates)

Citrate enhances inhibitory effects

27
Q

allosteric effectors of PFK-1: What do ADP and AMP do?

A

The potent stimulator of PFK-1

Represent a cell deficient in ATP

Activate PFK-1 by increasing affinity for fructose-6-phosphate

28
Q

What activates PFK-1?

A

Fructose-2,6-bisphosphate

29
Q

How is Fructose-2,6-bisphosphate formed?

A

Formed from fructose-6-phosphate by phosphofructokinase-2 (PFK-2)

Which increases affinity of PFK-1 for fructose-6-phosphate

Decreases inhibitory effect of ATP

30
Q

What is PFK-2?

A

A bifunctional enzyme regulated by covalent modification

Tandem enzyme

A kinase activity (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2) present on the same polypeptide

A phosphorylation domain controls the activity of both enzyme activities

31
Q

Fructose-2,6-bisphosphate is also a potent allosteric inhibitor of?

A

Fructose-1,6-bisphosphatase

Covalent modifications regulate fructose-2,6-bisphosphate levels in response to hormonal signals

32
Q

Fructose-1,6-bisphosphatase activity is also controlled by?

A

Allosteric effectors which prevent substrate cycling

Many activators of PFK-1 inhibit fructose-1,6-bisphosphatase

Inhibitors of PFK-1 activate fructose-1,6-bisphosphatase

33
Q

Without regulation of fructose-6-phosphate to fructose-1,6-bisphosphate, what would happen?

A

The net result would be a futile cycle

Energy from ATP hydrolysis would be liberated as heat

Futile cycling through to be responsible for such conditions as malignant hyperthermia

Possibly important means of flux control during excessive exercise

Also an important factor in heat generation in insects

34
Q

What isoenzymes exhibit a sigmoidal response to phosphoenolpyruvate (PEP)?

A

Liver, kidney, muscle and erythrocyte isoenzymes

35
Q

Whats involved in the regulation of pyruvate kinase?

A

Allosterically activated by Fructose-1,6-bisphosphate

Allosterically inhibited by ATP

Regulation ensures full utilisation of glycolytic intermediates

Activity curve with fructose-1,6-bisphosphate is hyperbolic

Maximally active at physiological

High [ATP] lowers affinity for PEP

Alanine, acetyl-Coa and long-chain fatty acids are also inhibitors

36
Q

pyruvate kinase isoenzymes present in?

A

Liver and intestinal cells are also regulated by covalent modification

37
Q

Explain Phosphorylation by protein kinase A?

A

In response to the effect of glucagon

Results in a less active form of pyruvate kinase

38
Q

Explain Transcriptional regulation

A

Levels of pyruvate kinase decrease during periods of starvation

Increase after introduction to a high carbohydrate diet

This is the result of changes in the rate of transcription of the pyruvate kinase gene

39
Q

What is the fate of pyruvate?

A

ATP production from glyceraldehyde-3-phosphate in glycolysis -> reduction of NAD to form NADH

Cells only have limited amounts of NAD

If NAD is not regenerated, glycolysis will stop

Passing of reducing equivalents to electron transport chain (aerobic conditions)

Under anerobic conditions metabolism of pyruvate regenerates NAD

40
Q

Activity changes in response to?

A

Concentration of substrate, product or different effector molecules

41
Q

Why is Allosteric regulation important for control of metabolic pathways?

A

1) Small changes in [S] can result in large changes in activity: Helps to maintain homeostasis
2) Permits regulation by effectors totally dissimilar to substrates or products: End products of pathways can exert effects
3) Permits interaction of effectors formal several pathways

Molecular bioscience (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions