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Biochemistry > Glycolsis > Flashcards

Glycolsis Flashcards

1
Q

Which 2 peptide hormones control the concentration of glucose in plasma?

A

Insulin from beta cells
Glucagon from alpha cells
Both from islets of langerhans

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2
Q

What other name can be used to refer to glycolysis?

A

Embden-Meyerhof-Parnas (EMP) pathway.

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3
Q

Where does glycolysis take place?

A

Cytosol. It is the first step in cellular respiration

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4
Q

What is the significance of glycolysis?

A
  1. major pathway of carbohydrate metabolism that occurs in almost all organisms from plants, microbes to mammals.
  2. can happen in aerobic and anaerobic conditions.
  3. Provides energy as ATP by oxidising glucose

4.provides intermediates for other metabolic pathways

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5
Q

What is the overall word description of glycolysis

A

Glucose, a 6-C molecule, is split into two molecules of pyruvate, 3-carbon compound

• Pyruvate is the end product of anaerobic glycolysis in cells without MITOCHONDRIA and an adequate supply of OXYGEN.

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6
Q

When/where does anaerobic glycolysis occur?

A

In cells without mitochondria or under anaerobic conditions I.e. strenuous exercise leading to an oxygen debt

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7
Q

What is the importance of anaerobic glycolysis?

A

It allows energy to be produced in cells lacking mitochondria eg RBC

It also allows energy to be produced in the absence of oxygen

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8
Q

What is the product of anerobic glycolysis?

A

Glucose is broken down into pyruvate which is further broken down into lactate, all in the absence of oxygen

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9
Q

Name the 2 types of glucose transporters

A
  1. Na+-independent, facilitated diffusion transport system
  2. Na+- monosaccharide co-transporter system.
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10
Q

What is SGLT?

A

Sodium-dependent glucose co- transporter

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11
Q

Where is SGLT found?

A

On the apical/luminal side of Intestinal cells and PCT of kidneys

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12
Q

What maintains the sodium concentration gradient used by SGLT?

A

Na+/K+ ATPase.

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13
Q

How does SGLT 1 function?

A

2 Na ions move into the cell down its concentration gradient, taking 1 glucose with it in the small intestine and kidney

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14
Q

How does SGLT 2 Function?

A

1 Na molecule moves down its concentration gradient into the cell, taking along 1 glucose molecule as well

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15
Q

What % of reabsorbed filtered glucose in the PCT does SGLT 1 and 2 account for?

A

3% and 97% respectively

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16
Q

How many Na+ independent facilitated diffusion transporters are there? What are their names?

A

There are 4 types in total
*GLUT-1
*GLUT-2
*GLUT-3
*GLUT-4

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17
Q

Which Na+ independent glucose transporters do NOT require insulin to function?

A

GLUT 1,2 &3

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18
Q

Which Na Independent glucose transporters are found in most human cells, CNS, placenta and Also have a high affinity for glucose?

A

GLUT-1 and GLUT-3

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19
Q

Which glucose transporter is found in the Cornea, BBB and fetal tissue?

A

GLUT-1

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20
Q

Which glucose transporters is found in the liver, kidney, pancreatic beta cells and the small intestine?

A

GLUT-2

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21
Q

Where is GLUT 4 located in the body?

A

In AHS- Adipocytes, Heart muscle and Skeletal muscle

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22
Q

What are the functions of GLUT-2?

A

*Transports ALL monosaccharides.

• senses Glucose .

• acts as a Bidirectional transporter, allowing hepatocytes to take up glucose for glycolysis and release glucose during gluconeogenesis and glycogenolysis.

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23
Q

What is the affinity of GLUT 2 for glucose?

A

Low, meaning glucose only diffuses through this insulin independent transporter at at high levels

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24
Q

What peptide hormone activates GLUT-4?

A

of active GLUT-4 increases with insulin

Insulin— stimulates movement of GLUT-4 which is stored in vesicles to plasma membranes for glucose uptake

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25
Q

What else can cause the translocation of GLUT-4 to plasma membrane?

A

Physical exercise may cause the translocation of GLUT 4 in an insulin INdependent way in skeletal muscle

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26
Q

What are the 2 phases of glycolysis ?

A

Preparatory/ Investment phase and Payoff phase respectively

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27
Q

At which point is ATP used in glycolysis?

A

In the first priming reaction, where glucose is phosphorylated into Glucose-6-phosphate

AND

In the second priming reaction where Fructose-6-phosphate phosphorylated into Fructose 1,6-Biphosphate

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28
Q

Which reaction first forms ATP??

A

Reaction 7 biphosphoglycerate catalysed by phosphoglycerate kinase into 3-phosphoglycerate

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29
Q

Which second reaction forms ATP?

A

Reaction 10: phosphoenol pyruvate catalysed by pyruvate kinase into pyruvate

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30
Q

Which reaction produces water as biproduct ?

A

Reaction 9: dehydration of 2-phosphoglycerate catalysed by enolase into phosphoenol pyruvate (PEP)

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31
Q

Which reaction produces NADH and hydrogen?

A

Reaction 6: oxidation of glyceraldehyde-3-phosphate catalysed by glyceraldehyde-3-phosphate dehydrogenase into 1.3 biphosphoglycerate

Also the FIRST redox reaction of glycolysis

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32
Q

What are the 2 products of the cleavage of Fructose 1,6 biphosphate?

A

Glyceraldehyde 3 phosphate (G3P) and dihydroxyacetone phosphate (DHAP)

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33
Q

Why must Dihydrocyacetpne be immediately isomerised to form glyceraldehyde -3 phosphate?

A

For the second NADH molecule to form from the dehydration reaction of the second glyceraldehyde molecule. NADH if formed when glyceraldehyde-3-phosphate is converted to 1.3 biphosphoglycerate

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34
Q

Which reactions are reversible in glycolysis?

A

Reaction 1, 2, 4, 5, 6, 7, 8 and 9

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35
Q

Which reaction is the first committed (I.e irreversible) step in glycolysis?

A

Reaction 3: phosphorylation of fructose 6-phosphate to Fructose 1,6-biohosphate

36
Q

Which two aldose and ketose products are formed during glycolysis?

A

Glyceraldehyde-3-phosphate and dihydroxyacetone

37
Q

Which reactions require a coenzyme Mg2+?

A

Reaction 1, 2,3, 7, 8 and 10

38
Q

Which reaction of the first REDOX reaction?

A

Reaction 6: dehydration of glyceraldehyde 3-phosphate into 1,3 biphosphoglycerate

39
Q

What pathology inhibits glyceraldehyde 3-phosphate dehydrogenase? How?

A

Hyperglycemia, it promotes overproduction of reactive oxygen species (superoxide) which activates poly(ADP-ribose) polymerase.

ThisenzymeaddsmultipleADP-ribosemoleculestothefreesulfhydryl groups of active site cysteine residues of glyceraldehyde 3-phosphate dehydrogenase, causing inhibition

40
Q

Give an example of substrate level phosphorylation (SLP)?

A

Reaction 7. Synthesis of 3-Phosphoglycerate with the formation of ATP from 1.3 biphosphoglycerate under the action of phosphoglycerate kinase

41
Q

Explain the mechanism of SLP?

A

SLP is a mechanism of ATP formation which involves the transfer of a phosphate (Pi) from an energy rich metabolic intermediate to ADP to form ATP.

the donor molecule must be a high energy phosphate containing compound for SLP to happen

the energy released during the hydrolytic release of the Pi must be high enough to attach the Pi to ADP.

42
Q

How does arsenic poisoning it affect the production of ATP in glycolysis ?

A

Arsenate prevents ATP production without inhibiting the pathway itself.

Due to its structural similarity to phosphate, it interacts with the Cys-SH group of glyceraldehyde 3-phosphate dehydrogenase, forming a complex (1-arseno- 3-phosphoglycerate) that spontaneously hydrolyzes to form 3- phosphoglycerate.

By bypassing the synthesis of 1,3- BPG, ATP is not formed by phophoglycerate kinase.

Therefore there is no net ATP synthesis occurring when glycolysis takes place in the presence of arsenate

43
Q

Which reactions only require an enzyme to occur?

A

Reaction 4, 5 and 9!dealing with aldolase, triode phosphate isomerase and enolase respectively

44
Q

What are the key enzymes of Glycolysis?

A

Hexokinase (Glucokinase), Phosphofructokinase-1, and Pyruvate kinase.

45
Q

Why are the enzymes that regulate Glycolysis know as key enzymes?

A

They regulate the rate of glycolysis according to physiological needs of the body

46
Q

What activates hexokinase? What stimulates hexokinase synthesis?

A

AMP and ADP: adenosine monophosphate and adenosine diphosphate

Insulin! Therefore ⬇️ blood glucose levels

47
Q

What inhibits hexokinase function? What inhibits hexokinase formation?

A

its product, glucose-6-phosphate

Glucagon inhibits hexokinase synthesis therefore inhibiting the first step of glycolysis. This leads to ⬆️ blood sugar levels

48
Q

What inhibits glucokinase?

A

fructose-6-phosphate.

49
Q

What and how is PFK-1 inhibited?

A

Elevated levels of ATP and citrate.

high proton concentration. This make sures there is no cell damaging effect of decreased pH as a result of anaerobic pyruvate metabolism.

50
Q

What and how is PFK-1 activated?

A

is activated allosterically by high concentrations of AMP and fructose 2,6-bisphosphate.
S6
• Fructose 2,6-bisphosphate is the most potent activator of PFK-1 and can activate the enzyme even when ATP levels are high.

51
Q

What inhibits pyruvate kinase?

A

ATP and alanine.

52
Q

What activates pyruvate kinase?

A

fructose 1,6-bisphosphate.

53
Q

What is the first reaction of glycolysis?

A
  1. Phosphorylation of Glucose: with the help of ATP, Mg2+ and hexokinase

: Phosphorylated sugar molecules do not readily cross cell membranes, because there are no specific transporters for these compounds.
• They remain effectively trapped in the cells.
• Phosphorylation of glucose ensure the intracellular concentration of glucose is low allowing for the continued uptake of glucose by the cells.

54
Q

What is the 2nd reaction of glycolysis?

A
  1. Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate in the presence of phosphoglucose isomersae and Mg2+
55
Q

What is the 3rd reaction of glycolysis?

A

Phosphorylation of Fructose 6-Phosphate to Fructose 1,6- Bisphosphate in the presence of ATP, Mg2+ and PFK-1

56
Q

What is the 4th reaction of glycolysis?

A
  1. Cleavage of Fructose 1,6-Bisphosphate in the presence of aldolase
57
Q

What is the 5th reaction in glycolysis?

A
  1. Isomerization of the Triose Phosphates: dihydroxyacetone phosphate, is rapidly and reversibly converted to glyceraldehyde 3-phosphate by the fifth enzyme of the sequence, triose phosphate isomerase

results in the net production of two molecules of glyceraldehyde 3-phosphate from the cleavage products of fructose 1,6- bisphosphate.

58
Q

What is the 6th reaction of glycolysis?

A
  1. Oxidation of Glyceraldehyde 3-Phosphate to 1,3-Bisphosphoglycerate in the presence of G3PD

First pay off reaction as NADH is formed
First redox reaction

59
Q

What is the 7th reaction of glycolysis?

A
  1. Synthesis of 3-Phosphoglycerate with the formation of ATP from 1,3- BPG in the presence of phosphoglycerate kinase and Mg2+
60
Q

What is the 8th reaction of glycolysis?

A
  1. Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate in the presence of phosphoglycerate mutase and Mg2+
61
Q

What is the 9th reaction of glycolysis?

A
  1. Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate
    (PEP) in the presence of enolase

This reaction produces water

62
Q

What is the 10th reaction of glycolysis?

A
  1. Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP, in the presence in pyruvate kinase, forming pyruvate
63
Q

What happens to the net products of aerobic glycolysis

A

Pyruvate gets combined with oxaloacetate to form citrate in the presence of citrate synthase

64
Q

What is the energy yield of aerobic glycolysis?

A

2 net ATP since 2 were used up
2 NADH molecules

65
Q

What is the energy yield of anaerobic glycolysis?

A

2ATP

66
Q

Write short notes on pyruvate kinase deficiency

A

The normal, mature erythrocyte lacks mitochondria and is completely dependent on glycolysis for production of ATP.

• ATP is required to meet the metabolic needs of the red blood cell, and to fuel the pumps necessary for the maintenance of the biconcave, flexible shape of the cell, which allows it to squeeze through narrow capillaries.

• The premature death and lysis of red blood cells results in hemolytic anemia.

• Symptoms of PK deficiency is mild to severe chronic hemolytic anemia, icterus, fatigue, jaundice, and elevated bilirubin levels.

67
Q

Why is glucose-6-phosphate an important compound?

A

can be diverted to many metabolic pathway such as
glycolysis, gluconeogensis, pentose phosphate pathway, and glycogenesis).

68
Q

Write short notes on the function of Glucokinase regulatory protein

A

Glucokinase regulatory protein
(GKRP) in the liver regulates the activity of glucokinase through reversible binding. In the presence of
fructose 6- phosphate, glucokinase is translocated into the nucleus and binds tightly to the regulatory
protein, thus rendering the enzyme inactive. When glucose levels in the blood (and also in the
hepatocyte, as a result of GLUT-2) increase, glucokinase is released from the regulatory protein, and the
enzyme re-enters the cytosol where it phosphorylates glucose to glucose 6-phosphate. GKRP also acts as
a competitive inhibitor, competeing with glucose to bind to the active site of glucokinase.

69
Q

What potently inhibits enolase?

A

Fluoride

70
Q

What are the two ways in which Glycolysis can be regulated?

A

hormonal (via cAMP), or it can be allosterically (via reactant or product).

71
Q

Which enzyme has a high affinity for glucose?

A

Hexokinase has high affinity for glucose. This ensures that even at low glucose concentration glycolysis
occurs in extrahepatic tissues

72
Q

Which enzyme has a low affinity for glucose?

A

Glucokinase has low affinity for glucose. This means that it will bind to glucose only when the glucose
concentration is very high.

73
Q

Which amino acid can pyruvate be converted into

A

Alanine

74
Q

What does the formation citrate and alanine signal

A

Its high-level signals that
the substrate requirements for CAC (critic acid cycle) has been met.

Alanine formation signals that the substrate requirements for other
metabolic pathways have been met

75
Q

Which product is NOT an intermediate of glycolysis

A

F2,6BP

76
Q

When does oxidative decarboxylation of pyruvate occur?

A

If oxygen is available or in cells with mitochondria,

77
Q

What are the products of the Oxidative decarboxylation of pyruvate?

A

acetyl-CoA and carbon dioxide, producing more ATP molecules.

78
Q

Which enzyme is used in Oxidative decarboxylation of pyruvate?

A

pyruvate dehydrogenase

79
Q

Why is the previous irreversible reaction important?

A

Pyruvate dehydrogenase irreversibly converts pyruvate into acetyl CoA, a major fuel for the TCA cycle and the building block for fatty acid synthesis.

80
Q

How is a the limited amount of NAD+ which comes from NADH formed?

A

• oxidation of NADH via the respiratory chain (aerobic).
• NADH-linked conversion of pyruvate to lactate (anaerobic).

81
Q

Which enzyme catalyses the reaction of the reduction of pyruvate to lactate?

A

lactate dehydrogenase

82
Q

What else is needed for the reduction of pyruvate to lactate other than the enzyme lactate dehydrogenase?

A

NADH +H to form NAD+

83
Q

Where does reduction of pyruvate to lactate notmallly occur? Why?

A

Where? lens and cornea of the eye, kidney medulla, testes, leukocytes and red blood cells

Why? these are all poorly vascularized and/or lack mitochondria.

84
Q

How does lactate form in muscle?

A
85
Q

What if the function of glucokinase in the liver and beta pancreatic cells?

A

In liver parenchymal cells and β-cells of the pancreas, glucokinase is the predominant enzyme responsible for phosphorylation of glucose.
• The function of glucokinase in the liver is to provide glucose 6-phosphate in excess of requirements for glycogen synthesis.
• in pancreatic β-cells, it acts as glucose sensor and regulates the secretion of insulin.

Biochemistry (6 decks)

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