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Biochemistry 2 > Glucose and AA Metabolism > Flashcards

Glucose and AA Metabolism Flashcards

1
Q

What are 4 products that glucose can be turned into and what is each product’s function?

A
  1. Glycogen, starch, sucrose –> storage
  2. Pyruvate –> Oxidation via glycolysis
  3. Extracellular matrix and cell wall polysaccharides –> Synthesis of structural polymers
  4. Ribose 5 Phosphate –> Oxidation via pentose phosphate pathway
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2
Q

What are the 4 pathways of glucose utilization?

A
  1. Glycolysis - glucose is degraded to pyruvate
  2. Gluconeogenesis - glucose is formed from a non-COH source
  3. Glycogenesis - glycogen is polymerized from glucose units
  4. Glycogenolysis - glycogen is degraded to glucose units
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3
Q

What are the two phases of glycolysis?

A

Preparatory phase, payoff phase

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4
Q

In the preparatory phase, when do the first and second priming reactions take place?

A

1st: Glucose to G-6-P via hexokinase. ATP used up
2nd: F-6-P to F-1,6-P via PFK-1. ATP used up

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5
Q

What is happening as aldolase converts F-1,6-BiP into Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate?

A

Cleavage of 6-C sugar phosphate to two 3-C sugar phosphates

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6
Q

What enzyme in glycolysis is also found on FA synthesis? What phase is it found in?

A

Glycerol-3-phosphate dehydrogenase

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7
Q

What is special about the conversion of 2NAD(+) –> 2NADH + 2H(+) from (2)Glyceraldehyde-3-phosphate to (2)1,3-Bisphosphoglycerate?

A

The NADH is used as the energy source, not ATP.

Oxidation & phosphorilation!!

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8
Q

What is the 1st ATP-forming reaction in glycolysis? The 2nd?

A

1st: (2)1,3-Bisphosphoglycerate –> (2)3-Phosphoglycerate
2nd:
(2)Phosphoenolpyruvate –> (2)Pyruvate

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9
Q

What is another way of calling an ATP-forming reaction in glycolysis?

A

Substrate-level phosphorylation

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10
Q

Define the Preparatory Phase?

A

Phosphorylation of glucose and its conversion to glyceraldehyde-3-phosphate

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11
Q

Define the Payoff phase?

A

Oxidative conversion of glyceraldehyde-3-phosphate to pyruvate and the coupled formation of ATP and NADH

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12
Q

What does the initial phosphorylation of glucose ensure?

A

That the pathway intermediates remain in the cell.

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13
Q

In the 1st step of glycolysis, phosphorylation occurs on which C?

A

C-6

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14
Q

In the 1st step of glycolysis, why does phosphorylation not occur on C-1?

A

C-1 is a carbonyl group and can not be phosphorylated.

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15
Q

Isomerization from G-6-P to F-6-P does what exactly?

A

It moves the carbonyl to C-2. Now C-1 is a hydroxyl group that can be later phosphorylated.

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16
Q

From F-6-P to F-1,6-BiP, phosphorylation occurs on what C?

A

C-1

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17
Q

What does the relocation of the carbonyl group onto C-2 facilitate?

A

C-C bond cleavage at the right location to yield two 3-Carbon products.

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18
Q

What reaction occurs to split Fructose-1,6-biphosphate into two 3-carbon compounds?

A

Reverse of an aldol condensation

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19
Q

What is the oxidative phosphorylation of Glyceraldehyde-3-phosphate a prerequisite for? What is produced?

A

ATP production. NADH is produced.

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20
Q

What happens from 3-Phosphoglycerate to 2-phosphoglycerate. What does this do?

A

The remaining phosphoryl group moves from C-2 to C-3. This sets up the final steps of the pathway.

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21
Q

What happens between 2-Phosphoglycerate and Phosphoenolpyruvate? What does this do?

A

Dehydration which activates the phosphoryl for transfer to ADP in the final step.

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22
Q

During what steps in the payoff phase is ATP produced? NADH produced?

A

ATP

  • 1,3-Biphosphoglycerate –> 3-Phosphoglycerate
  • Phosphoenolpyruvate –> Pyruvate
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23
Q

Net Yield formula of Glycolysis

A

1glucose + 2ATP + 2NAD(+) + 4ADP + 2Pi = 2Pyruvate + 2NADH + 2H(+) + 2ATP + 2H2O

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24
Q

How many ATP’s are used during Preparatory phase? How many ATP’s are produced during the Payoff phase? Net?

A
  • 2
  • 4
  • 2
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25
Q

What are the 3 different paths that the 2 Pyruvate produced from glycolysis can take?

A
  1. 2 Ethanol + 2 CO2
  2. Acetyl-CoA –> 4 CO2 + 4 H2O
  3. 2 Lactate
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26
Q

Under what conditions does pyruvate turn into 2 Ethanol + 2 CO2?

A

Hypoxic or anaerobic conditions.

Fermentation to ethanol and yeast.

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27
Q

Under what conditions does pyruvate turn into 2 Acetyl-CoA, what else is producted? What pathway does it then go through to become 4CO2 + 4H2O?

A

Aerobic conditions, 2CO2 are also produced.

Citric acid cycle.

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28
Q

Under what conditions does pyruvate turn into 2 Lactate? Where does this normally happen in nature?

A

Anaerobic conditions.
Vigorously contracting muscle, erythrocytes, some microorganisms. Happens when animal tissues cannot be supplied with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis

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29
Q

Which type of cells produce lactate from pyruvate even under aerobic conditions? Via which enzyme?

A

Erythrocytes (have no mitochondria). Vial lactate dehydrogenase

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30
Q

How does lactate dehydrogenase modify pyruvate? Draw it.

A

Forms the L-isomer of lactate: L-lactate.

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31
Q

What is the change in free energy of the Pyruvate –> Lactate reaction? What does this mean?

A

-25.1 kJ/mol. Lactate formation is strongly favored.

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32
Q

What is the net production of NADH in lactate formation from pyruvate?

A

Because 2 molecules of NADH were produced in the payoff phase of glycolysis, there is no net production of NADH. Glycolysis produces 2NADH, then fermentation uses those two NADH.

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33
Q

When oxygen is not available in animal cells…

A
  1. NAD+ is required for glycolysis to continue.
  2. NAD+ is generated by converting pyruvate to lactate.
  3. Erythrocytes convert pyruvate to lactate then carry the lactate to the liver where it is converted to glucose during muscle recovery.
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34
Q

What are the 5 primary sources of glucose into the preparatory stage of glycolysis? What are their enzymes?

A

Lactose (lactase), Trehalose (trehalase), Sucrose (sucrase), Dietary glycogen/starch (alpha-amylase), Endogenous glycogen (phosphorylase)

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35
Q

Where does the digestion of starch begin in our body? What enzyme is present and what does it do?

A

In the mouth. Alpha-amylase hydrolyzes the (alpha-1,4) glycosidic linkages of starch. Water is used!! (not Pi)

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36
Q

Where does alpha-amylase become inactivated in the body?

A

Stomach because of low pH. New alpha-amylase gets secreted by the pancreas into the small intestine.

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37
Q

What does dietary glycogen/starch become before it becomes G-6-P?

A

Dietary glycogen/starch (alpha-amylase) –> D-Glucose (hexokinase) –> Glucose-6-phosphate.

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38
Q

During glcogenolysis, what part of the glycogen molecule becomes broken down into glucose? What enzyme activates this reaction?

A

The non-reducing end of the glycogen molecule. Enzyme: glycogen (starch) phosphorylase.

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39
Q

What are the two products of glycogenolysis?

A

Glucose-1-phosphate +

Glycogen (n-1) glucose units.

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40
Q

For what 6 body systems is glucose the main/only source of fuel?

A

Brain, nervous system, erythrocytes, testes, renal medulla, and embryo tissue.

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41
Q

When is

gluconeogenesis required? 3 examples?

A

When glucose stores are not sufficient/depleted. Between meals, during long fasts, after vigorous exercise (needed for recovery).

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42
Q

What does gluconeogenesis do?

A

Converts pyruvate and related 3- & 4- C compounds to glucose. Basically reverse glycolysis.

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43
Q

In what 3 locations does gluconeogenesis take place in the body? Which is the main spot?

A

Liver (majority), renal cortex (cortex of kidney), and epithelial cells that line the small intestine.

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44
Q

What happens to the lactate produced by anaerobic glycolysis in skeletal muscles after vigorous exercise? What is another name for this process?

A

It goes back to the liver where it is converted to glucose via gluconeogenesis. This glucose then travels back to the muscles & is converted to glycogen. Cori cycle.

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45
Q

What 3 steps of gluconeogenesis use different enzymes than glycolysis?

A
  1. Pyruvate –> Phosphoenolpyruvate
  2. Fructose-1,6-bisphosphate –> Fructose-6-phosphate
  3. Glucose-6-phosphate –> Glucose
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46
Q

What enzyme is different in gluconeogenesis and glycolysis in the step involving Phosphoenolpyruvate and Pyruvate? At what stage is there an extra intermediate in gluconeogenesis that is not in glycolysis?

A

Glycolysis:
Phosphoenolpyruvate –> Pyruvate. Enzyme: pyruvate kinase (produces 2 ATP)

Gluconeogenesis:

  1. Pyruvate –> Oxaloacetate. Enzyme: Pyruvate carboxylase (2 ADP produced).
  2. Oxaloacetate –> Phosphoenolpyruvate. Enzyme: PEP carboxykinase (2 GDP produced + CO2).
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47
Q

What is the abreviation for Phosphoenolpyruvate?

A

PEP

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48
Q

Where in the cell does the Pyruvate to Oxaloacetate reaction take place?

A

Mitochondria

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49
Q

Where in the cell does the oxaloacetate to PEP reaction take place?

A

Cytosol/mitochondria

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50
Q

Pyruvate —> oxaloacetate reaction requires what coenzyme?

A

Biotin

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51
Q

What is biotin?

A

A vitamin

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52
Q

Which intermediates of the TCA cycle can enter gluconeogenesis?

A

All of them!

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53
Q

What is the most common fate of G-6-P? What is an alternative fate?

A

Glycolysis. Pentose phosphate pathway

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54
Q

What is another term for pentose phosphate pathway?

A

Hexose monophosphate pathway.

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55
Q

What is the electron acceptor in the PPP? What does it make?

A

NADP+ which yeilds NADPH.

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56
Q

What type of cells undergo the pentose phosphate pathway? Such as? To produce what?

A

Rapidly dividing cells. Bone marrow, skin, intestinal mucosa, tumors!

Products: RNA, DNA, ATP, NADH, FADH2, Coenzyme A.

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57
Q

What type of cells require the NADPH produced by the PPP? For what 2 reasons do these cells require NADPH?

A

Tissues that carry out extensive fatty acid synthesis (adipose, liver, lactating mamary glands) or
extensive cholesterol synthesis and steroid hormones (liver, adrenal glands, gonads). Erythrocytes and eye cells.

Needed for reductive biosynthesis or to counter the effects of oxygen radicals.

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58
Q

What is the 1st reaction of the PPP + enzyme? Biproduct

A

G-6-P –> 6-phosphogluconate.

Enzyme: G6P Dehydrogenase.

Biproduct: NADPH

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59
Q

What does the NADPH produced in the 1st reaction of the PPP donate its electrons to? What enzyme is involved?

A

GSSG –> 2 GSH

Enzyme: Glutathione reductase

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60
Q

What is the second reaction of the PPP + enzyme? Biproduct?

A

6-Phosphogluconate –> Ribulose-5-Phosphate.

Enzyme: 6-phosphogluconate-dehydrogenase

Biproduct: NADPH

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61
Q

What does the NADPH produced in the 2nd reaction of the PPP donate its electrons to? What is this an example of?

A

Precursors –> fatty acies, sterols, etc.

Example of reductive biosynthesis

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62
Q

What is the 3rd step of the PPP? Enzyme?

A

Ribulose-5-Phosphate –> Ribose-5-phosphate.

Enzyme: Phosphopentose isomerase.

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63
Q

Ribose-5-Phosphate is a precursor for what?

A

Nucleotide synthesis (Nucleotides, coenzymes, DNA, RNA)

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64
Q

Why would tissue cells only undergo the non-oxidative phase instead of the oxidative phase?

A

They mainly just need NAHPH, not so much nucleotide production

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65
Q

What is recycled in the non-oxidative phase of the pentose phosphate pathway? Enzyme?

A

Ribulose-5-phosphate is recycled to G6P.

Enzyme: Transketolase, transaldolase

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66
Q

List the formation stages from O2 to Oxidative damage to lipids, proteins, DNA? What are additives & biproducts along the way?

A

Oxygen [O2] –> Superoxide Radical [O2-] –> (((2H+ & e- comes in))) –>
Hydrogen peroxide [H2O2] –> (((H+ & e- come in))) (biproduct: H2O) –>
Hydroxyl Radical [OH] –> Oxidative damage to lipids, proteins, DNA

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67
Q

How does the formation of 2GSH to GSSG prevent oxidative damage? Enzyme?

A

Adds 2 hydrogens to H2O2 –> 2H2O.

Enzyme: Glutathione peroxidase

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68
Q

How does 2GSH prevent oxidative damage?

A

Binds to [*OH], inhibiting oxidative damage to lipids, proteins, DNA

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69
Q

How is the PPP regulated (what inhibits it)? What is the result?

A

When NADH is forming faster than it is being used for biosyhtnesis and glutathione reduction, [NADPH] rises and inhibits the 1st enzyme in the PPP (G6P dehydrogenase).

Result: G6P is available for glycolysis.

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70
Q

Why do some of the reactions of gluconeogenesis use different enzymes at the same step of glycolysis?

A

Because they are the irreversible reactions of glycolysis: those catalyzed by hexokinase, PFK-1, & pyruvate kinase.

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71
Q

What is the change in free energy of glycolysis’s irreversible reactions?

A

Large and negative

72
Q

What 3 signaling molecules regulate expression/function of glycolytic enzymes?

A

Glucagon, epinephrine, insuline

73
Q

What is the purpose of the regulation of glycolysis?

A

Maintain a constant ATP level

74
Q

What are the isozymes of hexokinase? How are they all different?

A

Hexokinase I, II, III, IV.

Each encoded by a different gene.

75
Q

What is an isozyme?

A

Multiple forms of an enzyme that catalyze the same reaction but differ in amino acid sequence, substrate affinity, Vmax, and/or regulatory proteins.

76
Q

What are the 3 main characteristics of Hexokinase I & II?

A
  1. Predominant in muscle cells (myocytes)
  2. Very high affinity for glucose (activity reaches max saturation quickly)
  3. Allosterically inhibited by their product: G6P
77
Q

What does allosteric mean?

A

Enzyme changes conformation of active site by binding to a site that is not the active site.

78
Q

What is the difference between muscle cells and liver cells in terms of glucose usage?

A

Muscle cells: consume glucose & use it for energy production
Liver cells: maintain glucose homeostasis by consuming or producing glucose depending on the current [blood glucose]

79
Q

What is a liver cell called?

A

Hepatocyte

80
Q

What are the 3 characteristics of hexokinase IV?

???????????

A
  1. Predominant in the liver
  2. Low affinity for glucose. You need 5x the normal [glucose] for hexokinase IV to be fully saturated. At high [blood glucose] hexokinase IV is not fully saturated so continues to produce G6P. At low [blood glucose], the glucose generated by gluconeogenesis leaves the cell before affected by hexokinase, because the affinity is so low. ??????
  3. It is not inhibited by G6P
  4. Hexokinase IV can be inhibited by a regulatory protein (GKRP) & kept in nucleus when [fructose-6-phosphate] is high. When Glycolysis is activated, high [glucose] outcompetes F-6-P, & releases hexokinase IV to the cytosol.
81
Q

What is special about PFK-1 (Phosphofructokinase-1)?

A

It commits glucose to glycolysis. Major point of regulation

82
Q

What inhibits PFK-1? Activates it?

A

Allosteric inhibitors: ATP & citrate. The major role of glycolysis is to produce ATP, so when there is enough = inhibits.

Allosteric activators: High [AMP] & [ADP] + F-2,6-P

83
Q

What inhibits FBPase-1 (Fructose Bisphosphatase-1?)

A

AMP

84
Q

What does insulin promote?

A

Glycolysis, glycogenesis, and triglyceride synthesis

85
Q

What does glucagon promote? Inhibit?

A

Promotes gluconeogenesis.

inhibits glycolysis.

86
Q

What does the secretion of insulin activate? Which enzyme aids this reaction? Biproduct? Required?

A

PFK-2 via enzyme phospho-protein phosphatase.

Biproduct: Pi
Requires: H2O

87
Q

After its activation via the presence of insulin, what does PFK-2 do? What is PFK-2 dependent on?

A

it converts F-6-P into F-2,6-P. PFK-2 is ATP dependent, biproduct = ADP.

88
Q

What is special about the presence of Fructose-2,6-phosphate? This leads to???

A

It’s presence activates PFK-1. PFK-1 Converts F-6-P to F-1,6-biP —-> Glycolysis bound!!!

89
Q

What does the secretion of glucagon activate? Which enzyme aids this reaction? Biproduct?

A

FBPase-2 via enzyme cAMP-dependent protein kinase

Biproduct: ADP

90
Q

After its activation via the presence of glucagon, what does FBPase-2 do? Biproduct?

A

It converts F-2,6-biP back to F-6-P.

Biproduct: Pi

91
Q

What is special about the absence of F-2,6-biP?

A

Activates FBPase-1 which converts F-1,6-biP to F-6-P —> Gluconeogenesis bound!!!!

92
Q

How does Xylulose-5-phosphate regulate glycolysis/gluconeogenesis?

A

It activates phosphoprotein phosphatase 2A which dephosphorylates the PFK-2/FPBase-2 enzyme, activating PFK-2. This causes a rise in [F-2,6-P] –> glycolysis!!!

Inhibits gluconeogenesis

93
Q

Xylulose-5-phosphate is a product of what pathway?

A

PPP

94
Q

What allostericaly inhibits the enzyme (pyruvate kinase) in the reaction from PEP–>Pyruvate?

A

High [ATP, acetyl-CoA, long chain FA]. Also Alanine which is produced from pyruvate via transamination reaction (reversible)

95
Q

What allostericaly activates pyruvate kinase in the PEP–>Pyruvate reaction?

A

F16BP

96
Q

What enzyme is involved in the PEP–>Pyruvate reaction?

A

Pyruvate Kinase L/M

97
Q

What is a biproduct of the PEP–>Pyruvate reaction?

A

ATP = produced

98
Q

What isozyme of Pyruvate Kinase is effected by phosphorilation?

A

Liver form

99
Q

When is pyruvate kinase L inactivated? What is the mechanism? Effect?

A

When glucagon is released due to low blood [glucose]. Glucagon activates -cAMP-dependent protein kinase (PKA) which phosphorylates the Pyruvate Kinase L, inactivating it. This slows glucose use as fuel in the liver & allows the glucose to be used in other parts of the body (brain/other organs)

100
Q

When is [acetyl-CoA] high in the liver?

A

When there is sufficient FA for beta-oxidation

101
Q

How does acetyl CoA act as a regulator of pyruvate?

A

When [acetyl-CoA] is high, this means that further breakdown of glucose for fuel is not necessary. High [acetyl-CoA] inhibits the pyruvate dehydrogenate complex and activates the pyruvate carboxylase enzyme. This favors production of oxaloacetate and gluconeogenesis!

102
Q

What are the two fates of pyruvate?

A
  1. Acetyl-CoA –> TCA –> energy

2. Oxaloacetate –> gluconeogenesis

103
Q

Liver cells:

  1. Scientific name?
  2. Hexokinase isozyme?
  3. Glucose transporter?
A
  1. Hepatocytes
  2. Hexokinase IV
  3. GLUT 2
104
Q

What does ChREBP stand for? When is ChREBP unable to enter the nucleus?

A

Carbohydrate response element binding protein. When either its Tyr-P or Ser-P residues are phosphoryated - it remains in the cytosol.

105
Q

What enzyme dephosphoylates ChREBP? Which residue is dephosphorilated first?

What activates this enzyme?

What does this dephosphorilation allow?

A

Protein phosphatase (PP2A). This allows entry into the nucleus. Ser residue.

Xylulose-5-phosphate

Allows entry of ChREBP into the nucleus.

106
Q

Once into the nucleus, what enzyme further dephosphorylates ChREBP?

Which residue is dephosphorilated?

What does this dephosphorilation cause?

A

Protein phosphatase -PP2A (activated by Xylulose-5-phosphate)

Thr

ChREBP is now activated and binds to its partner protein Mlx.

107
Q

What does the ChREBP-Mlx complex bind to once it has come together?

A

ChoRE (carbohydrate response element)

108
Q

What is ChoRE?

A

A specific DNA sequence that is recognized by the transcription factor.

109
Q

What is the function of the ChREBP-Mlx complex?

A

Allow the transcription factor to turn on the synthesis of pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase (1st enzyme in the path to fatty acid synthesis)

110
Q

What is the purpose of FOXO1 on the transcriptional regulation of enzymes?

A

It promotes the synthesis of gluconeogenic enzymes, and suppresses the synthesis of the enzymes of glycolysis + PPP + triacylglycerol synthesis.

111
Q

When is FOXO1 activated?

A

When it is not phosphorilated

112
Q

What does FOXO1 act as in its unphosphorylated form?

A

A nuclear transcription factor.

113
Q

What enzyme dephosphorylates FOXO1?

A

phosphoprotein phosphatase

114
Q

What does FOXO1 do in response to insulin?

A

It leaves the nucleus and goes into the cytosole where it becomes phosphorilated by PKB, then bound to ubiquitin and degraded by proteasome.

115
Q

What prevents FOXO1 to become phosphorilated by PKB?

A

Glucagon!!! Allowing it to remain active in the nucleus

116
Q

What happens to FOXO1 that remains unphosphorilated or that becomes dephosphorilated?

A

In nucleus, it binds to a response element & triggers transcription of PEP carboxykinase, G6P & more…

117
Q

Slide 32

A

Skipped

118
Q

How do animals store glucose? How do plants store glucose?

A
  1. Glycogen

2. Starch

119
Q

In what 2 locations is glycogen primarily found?

A

Liver and muscle

120
Q

Glycogen makes up what % of the liver’s weight?

A

10%

121
Q

Where is glycogen stored?

A

Large cytosolic granules

122
Q

What is the elementary particle of glycogen?How many glucose residues is 1 beta-particle made up of? With how many non-reducing ends?

A

Beta-particle.

55,000 glucose residues! With 2,000 non-reducing ends!

123
Q

How many beta-particles is an alpha-rosette made up of?

A

20-40

124
Q

How fast are alpha-rosettes depleted after fasting in liver? Depleted after how much exercise in muscles?

A

12-24 h

1 h

125
Q

Amount of energy stored as glycogen relative to the amount of energy stored as fat?

A

Waaaaaayyyy less

126
Q

Glycogenesis is predominant in what type of cells?

A

Liver

127
Q

What is necessary for the polymerization of glucose into glycogen? What do these compounds do?

A

Sugar nucleotides which activate the anomeric carbon of a glucose molecule by attaching it to a nucleotide via a phospho-ester bond.

128
Q

What sugar nucleotide is used in the production of glycogen? What two molecules is this sugar nucleotide made up of?

A

UDP-glucose. Made up of D-Glucosyl group + Uridine

129
Q

What is the net reaction of the formation of UDP -glucose?

What acts as the nucleophile in the mechanism? What does this nucleophile attach?

A

Sugar phosphate + NTP —> NDP-sugar (sugar nucleotide) + 2Pi

Condensation reaction!!

The neg charged oxygen on the sugar phosphate serves as a nucleophile & attacks the alpha-phosphate of the neucleoside triphosphate.

130
Q

What is the first step in the formation of UDP Glucose? How are 2Pi formed?

A

Sugar phosphate + NTP –> Pyrophosphate (PPi) + Sugar Nucleotide (NDP-sugar).
^Enzyme: NDP-sugar pyrophosphorylase

Pyrophosphate (PPi) –> 2 Phosphate via enzyme inorganic pyrophosphatase.

131
Q

What is the function of the NDP-sugar pyrophosphorylase enzyme?

A

Removes 2 Pi’s from NTP and adds a sugar phosphate

132
Q

What does the enzyme glycogen synthase need in order to produce a new glycogen molecule?

A

A primer with at least 8 glucose residues!

133
Q

What two molecules initiate the formation of the primer for glycogenesis?

A

Glycogenin (a protein) + UDP-glucose

134
Q

What is special about Glycogenin?

A

It is both the primer on which the new chains are assembled and the enzyme that catalyzes their assembly.

135
Q

What is the very first step in the synthesis of a new glycogen molecule?

What happens next?

Biproduct?

How many times does this process occur?

A

Transfer of a glucose residue from UDP-glucose to the hydroxyl group (-OH) of Tyr-194 of glycogenin. (The -OH of glycogenin’s Tyr-194 attacks the C-1 of UDP-glucose).

The C-1 hydroxyl group of a new UDP-glucose attacks the C-4 of the terminal glucose molecule on the growing glycogen!

Biproduct: UDP

Up until there are 8 glucose residues.

136
Q

How many times does this primer process occur?

A

8

137
Q

What bonds are formed between the glucose molecules of glycogen? Due to what type of reaction?

A

(alpha1–>4) glycosidic bonds.

Condensation reaction

138
Q

What is the transfer of a gucose residue from UDP-glucose to the hydroxyl group of Tyr-194 of glycogen catalyzed by?

A

The protein’s intrinsic glucosyltransferase activity

139
Q

What enzyme elongates a glycogen chain? How?

How many glucose residues must already be present in the glycogen chain for glycogen synthase to become activated?

A

Glycogen synthase. By transffering the glucose residue of UDP-glucose to the non-reducing end of a glycogen branch.

n > 4

140
Q

An newly elongated glycogen has what formula?

A

n + 1 residues

141
Q

What is another name for the glycogen branching enzyme?

A

amylo(1–>4) to (1–>6)transglycosylase

142
Q

How many glucose residues down from the terminal one does the glycogen branching enzyme cleave? (textbook)

What glycosidic bond does the glycogen-branching enzyme cleave from the glycogen core?

A

6-7

4th one

143
Q

What kind of bond is formed at the new branch point during glycogen synthesis?

A

(alpha1–>6)

144
Q

What is the purpose of branching?

A
  1. Increase solubility
  2. Increase the number of non-reducing ends (to increase # of sites accessible to glycogen phosphorylase and glycogen synthase which only act at non-reducing ends)
145
Q

What are the 4 main steps to glycogenesis?

A
  1. Formation of UDP-glucose (NDP-sugar-pyrophosphorylase)
  2. Initial short chain synthesis (glycogenin –> up to 8 glucose molecules)
  3. Elongation (glycogen synthase)
  4. Branching (glycogen-branching enzyme)
146
Q

Each chain of glycogen has approximately how many glucose residues?

A

12-14

147
Q

What is glycogenolysis?

A

Glycogen breakdown

148
Q

What are the 3 enzymes involved in glycogenolysis?

A
  1. Glycogen phosphorylase
  2. Glycogen debranching enzyme
  3. Phosphoglucomutase
149
Q

What reaction does glycogen phosphorylase catalyze? What molecule is produced?

A

Attach of Pi on the (alpha1–>4) glycosidic linkage of two glucose residues at a non-reducing end of a glycogen molecule.

Glucose-1-phosphate

150
Q

When does glycogen phosphorylase stop repetitively breaking glucose off glycogen?

A

When it reaches the 4th glucose from a (alpha1–>6) branching point

151
Q

What is an essential cofactor of the glycogen phosphorylase reaction?

A

Pyridoxal phosphate

152
Q

How are the remaining 4 glucose residues near the branch removed after the terminal glucose residues have been removed by glycogen phosphorylase?

A

Via a debranching enzyme

153
Q

What is special about the debranching enzyme?

A

It is bi-functional.

  1. Transferase activity
  2. (alpha1–>6) glucosidase activity
154
Q

What happens during the transferase activity of the debranching enzyme?

A

a block of 3-glucose residues is shifted from the branch to the nearest non-reducing end – reattached in (alpha1–>4) linkage

155
Q

What happens during the (alpha1–>6) activity of the debranching enzyme?

A

The single glucose residue remaining at the branch point, in a (alpha1–>6) linkage, is then released as free glucose.

156
Q

Which enzyme produces glucose-6-phosphate from glucose-1-phosphate? How?

Where does G-6-P go after?

A

Phosphoglucomutase. This enzyme has a phosphorilated serine residue which it first donates to C-6 of glucose-1-phosphate, producing glucose-1,6-bisphosphate. The phosphate group on C-1 of glucose-1,6-bisphosphate is then transfered back to the enzyme.

157
Q

What is the function of the G6P formed from glucogenolysis in muscles? In liver?

A

Muscles: enter glycolysis and serve as an energy source to support muscle contraction

Liver: Release glucose into the blood when blood glucose levels drop

158
Q

What enzyme is required in the liver to convert G6P to Glucose? Where is it located? What kind of protein is this & what organelle does it belong to? Where is its active site located?

A

Glucose-6-phosphatase.

Liver (& kidney).

Integral membrane protein of the ER.

Active site is on the lumen side of the ER.

159
Q

How is the glucose-6-phosphate produced in the cytosol of the liver enter the lumen of the ER?

A

T1 specific transporter

160
Q

What is the function of glucose-6-phosphatase?

A

Hydrolyses G6P into Glucose + Pi

161
Q

How do glucose and Pi leave the lumen of the ER?

A

T2 - glucose transporter

T3 - Pi transporter

162
Q

How does glucose leave the hepatocyte?

A

GLUT2 transporter on plasma membrane

163
Q

What is the purpose of having the active site of G6P inside of the ER lumen instead of in the cytosol?

A

This separates the reaction from glycolysis that is happening in the cytosol (which would steal G6P)

164
Q

What are the active and inactive forms of the glycogen phosphorylase enzyme?

A

Active: Glycogen phosphorylase a

Inactive: Glycogen phosphorylase b

165
Q

Where is glycogen phosphorylase b predominantly found in the body?

A

Resting muscles

166
Q

What enzyme activates phosphorylase b to a? How is it activated?

A

Phosphorylase b kinase. Epinephrine (in muscle)/glucagon(in liver). Rise in cAMP activates PKA which phosphorylates ‘Phosphorylase b kinase’ on its 2 serine residues via 2 ATP’s –> formation of phosphorylase a kinase (active form) which stimulates glycogen breakdown.

167
Q

What does the activation of phosphorylase a kinase do in muscle vs liver?

A

Muscle: fuel for glycolysis to sustain fight or flight response signaled by epinephrine

Liver: glycogen breakdown fixes the low blood glucose signaled by glucagon –> releasing glucose

168
Q

What enzyme causes phosphorylase a to become inactivated back to phosphorylase b?

What was added? Biproduct?

A

Phosphorylase a phosphatase (PP1)

2 H2O molecules.
Biproduct 2 pi

169
Q

What are the active and inactive forms of the Glycogen synthase enzyme?

A

Active: glycogen synthase a

Inactive: glycogen synthase b

170
Q

Is the active form (glycogen synthase a) phosphorilated or de-phosphorilated? On what residues?

A

Dephosphorilated on the 3 serine residues

171
Q

What must happen in order to glycogen synthase to become phosphorylated (inactive)?

A

CKII needs to phosphorylate GSK3 to activate it, then GSK3 phosphorylates glycogen synthase

172
Q

What inhibits GSK3 and activates PP1?

A

Inuline

173
Q

What inhibits PP1? Activates?

A

Inhibit: Glucagon, epinephrine

Activate: Insulin, G6P, Glucose

174
Q

Look at slide 47, 48, 49. Discuss once mastered all card!!! :)

A

Talk about it out loud with someone

175
Q

How are each of the 8 glucose residues linked?

A

alpha(1–>4) glycosidic linkages.

176
Q

What is the function of the glucosyltransferase activity in the formation of the 8-glucolse long primer?

A

Brings glucosyl group (new glycogen molecule) to UDP-glucose

177
Q

What is the function of glycogen synthase?

How many residues does the activity of glycogen synthase require?

A

Catalyzes the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branched glycogen molecule.

At least 4!

Biochemistry 2 (8 decks)

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