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DEMS_BTRAN > UNIT2_CHO Metabolism NTK > Flashcards

UNIT2_CHO Metabolism NTK Flashcards

1
Q

In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:

succinyl CoA is used in _______ synthesis.

A

heme

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2
Q

In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:

oxaloacetate is used in process/pathway?

A

gluconeogenesis

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3
Q

In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:

oxaloacetate and α-ketoglutarate are used in __________ synthesis

A

amino acid

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4
Q

In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:

citrate is involved in the pathway of ________ synthesis

A

fatty acid

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5
Q

What is the order of the citric acid cycle?

A

“Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate.”

Citrate
Isocitrate
α-Ketoglutarate
Succinyl CoA
Succinate
Fumarate
Malate
Oxaloacetate
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6
Q

For each turn, the citric acid cycle produces how many GTP, ATP, NADH, FADH2, CO2?

A

For each turn, the citric acid cycle produces:

0 ATP
1 GTP
3 NADH
1 FADH2
2 CO2
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7
Q

For each turn, the citric acid cyclea total of ____ ATP molecules are made per acetyl CoA., due to the electron transport chain.

A

10-12 ATP

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8
Q

The α-ketoglutarate dehydrogenase complex is one of the three regulated steps of the citric acid cycle. It requires many cofactors, including:

A 
Vitamin B1 (Thiamine)
Vitamin B2 (Riboflavin)
Vitamin B3 (Niacin)
Vitamin B5 (Pantothenic Acid)
Lipoic acid
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9
Q

α-ketoglutarate dehydrogenase is inhibited by: (4)

A

NADH
Succinyl CoA
ATP
GTP

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10
Q

What enzyme converts α-ketoglutarate to succinyl-CoA?

A

The α-ketoglutarate dehydrogenase complex

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11
Q

During what steps of the TCA cycle are CO2 released?

A

Isocitrate to α-ketoglutarate

&

α-ketoglutarate to Succinyl-CoA

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12
Q

What enzyme oxidizes malate to oxaloacetate, and the cycle can begin anew?

A

Malate dehydrogenase

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13
Q

Mitochondrial _________nconverts fumarate to malate

A

fumarase

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14
Q

FADH2 is produced in the conversion of succinate to fumarate. This reaction is catalyzed by what enzyme?

A

succinate dehydrogenase

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15
Q

What enzyme is embedded in the inner mitochondrial membrane as complex II of the electron transport?

A

succinate dehydrogenase

aka Complex II

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16
Q

The __________ enzyme complex catalyzes oxidation of succinate to fumarate.

A

succinate dehydrogenase

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17
Q

______________ converts succinyl-CoA to succinate and CoA. In the process, substrate-level phosphorylation produces GTP.

A

Succinyl-CoA synthetase

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18
Q

Succinyl-CoA synthetase converts succinyl-CoA to _________ & _________. In the process, substrate-level phosphorylation produces GTP.

A

succinate and CoA

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19
Q

What enzyme catalyses that reaction where the 2nd CO2 is released?

A

α-ketoglutarate dehydrogenase

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20
Q

What enzyme catalyses that reaction where the 1st CO2 is released?

A

isocitrate dehydrogenase

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21
Q

The α-ketoglutarate dehydrogenase complex converts __________ to succinyl-CoA.

A

α-ketoglutarate

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22
Q

The ___________ enzyme complex converts α-ketoglutarate to succinyl-CoA.

A

α-ketoglutarate dehydrogenase

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23
Q

What reaction in the TCA cycle produces GTP?

A

Succinyl-CoA synthetase converts succinyl-CoA to succinate and CoA.
In the process, substrate-level phosphorylation produces GTP. The entire reaction is:

Succinyl CoA + Pi + GDP ↔ Succinate + CoA + GTP

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24
Q

What reaction in the TCA cycle produces FADH2?

A

Succinate to Fumarate via

Succinate dehydrogenase. (Complex II on the inner mitochondria membrane in the ETC)

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25
Q

What enzyme concerts PEP to pyruvate?

A

Pyruvate Kinase

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26
Q

What is formed after GA3P?

A

1,3-biphosphoglycerate (1,3BPG)

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27
Q

What is the enzyme that sequesters glucose within the cells of skeletal muscles?

A

Hexokinase

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28
Q

Glucokinase is a high-capacity isoenzyme of hexokinase expressed what organs?

It is induced by insulin and is a key component of insulin’s hypoglycemic effect.

A

in the liver and pancreas

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29
Q

What is the RDS of Glycolysis?

A

F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) by phosphofructokinase-1 (PFK-1)

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30
Q

In what cellular compartment does glycolysis occur?

A

Cytosol

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31
Q

What are the key enzymes that regulate Glycolysis?

A
  • Hexokinase
  • Glucokinase
  • Phosphofructokinase-1 (PFK-1)
  • Pyruvate Kinase
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32
Q

Is Hexokinase or Glucokinase inhibited by G-6-P? Why is this important?

A

Hexokinase is inhibited by G-6-P.

The regulation of Hexokinase by G6P prevetns the over consumption of ATP during the rxn.

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33
Q

What is the Km and V_max of Hexokinase?

What is the Km and V_max of Glucokinase?

What does this mean?

A

Hexokinase: Low Km=High Affinity & low capacity=low V_max

Glucokinase: High Km=Low affinity & high capacity=high V_max.

Also peripheral tissue to get glucose even in a fasted state.

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34
Q

Is Hexokinase or Glucokinase STIMULATED by insulin? Why is this important?

A

Glucokinase is stimulated by insulin!

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35
Q

What is MODY and what enzyme is defective?

A

Glucokinase genetic mutationson chromosome 7 may result in maturity-onset diabetes of the young (MODY).

Glucokinase, within the beta-cells of the pancreas, acts as a glucose sensor, thus when a mutation is present, impaired glucose sensation occurs leading to persistant hyperglycemia and impaired insulin secretion.

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36
Q

Glucokinase is further regulated by fructose-6-phosphate. Explain how?

A

F6P binds to the same receptor as glucokinase regulatory protein (GKRP), thereby enhancing GKRP’s ability to inhibit glucokinase.

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37
Q

Phosphofructokinase-1 activity is increased in the presence of what molecule? What type of regulation is this?

A

AMP

&

fructose-2,6-bisphosphate (F2,6BP)

which act as allosteric activators.

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38
Q

Phosphofructokinase-1 activity is decreased in the presence of what molecule?

A

Citrate and ATP (high energy state)

39
Q

Phosphofructokinase-2 (PFK2) / fructose-2,6-bisphosphatase (F26BPase) is a bifunctional enzyme regulating phosphofructokinase-1. PFK2 is favored under the following pathway: (6)

A
  1. High blood glucose causes insulin secretion
  2. Insulin activates protein phosphatase
  3. Protein phosphatase dephosphorylates PFK2
  4. PFK2 then predominates over F26BPase
  5. PFK2 synthesizes fructose-2,6-bisphosphate from fructose-6-phosphate
  6. F26BP is a potent activator of PFK-1
40
Q

Phosphofructokinase-2 / fructose-2,6-bisphosphatase is a bifunctional enzyme regulating phosphofructokinase-1. F26BPase is favored under the following pathway: (5)

A
  1. Low blood glucose elevates glucagon secretion
  2. Glucagon secretion causes phosphorylation of PFK-2 via cAMP pathway
  3. F2,6BPase activity now predominate
  4. F26BPase synthesizes fructose-6-phosphate from fructose-2,6-bisphosphate
  5. Lower concentrations of F26BP decreases the activity of PFK-1
41
Q

What increases Pyruvate Kinase activity?

A

presence of F1,6BP and PEP

42
Q

How is Pyruvate Kinase inhibited?

A

Allosterically, by ATP & Alanine

43
Q

Pyruvate kinase may also be inhibited by low blood glucose levels, allowing for PEP to enter gluconeogenesis via the following pathway: (4)

A
  1. Low Glucose levels detected.
  2. INcreased glucagon secretion.
  3. Increased cAMP and PKA activity
  4. Phosphorylation leads to inactivation of pyruvate kinase
44
Q

What molecule results from the carboxylation reaction of pyruvate?

A

Oxaloacetate

via Pyruvate carboxylase

45
Q

The majority of pyruvate is metabolized to lactate by lactate dehydrogenase in the following tissues:(6)

A
  • Cornea
  • Lens
  • Red blood cells
  • White blood cells
  • Kidney medulla
  • Testes
46
Q

What enzyme converts pyruvate to alanine and what is the cofactor that is needed?

A

alanine aminotransferase (ALT)

Transamination rxn.

Cofactor is Pyridoxal phosphate (vitamin B6 .

47
Q

Pyruvate can be converted to the following molecules and enter their associated pathways: (4 rxns)

A

1) acetyl-CoA → citric acid cycle
2) oxaloacetate → TCA cycle or gluconeogenesis
3) alanine → glucose-alanine cycle
4) lactate → Cori cycle (hepatic gluconeogenesis from lactate)

48
Q

How can pyruvate enter the Cori Cycle?

A

Pyruvate –> Lactate

via lactate dehydrogenase (LDH)

49
Q

Can pyruvate be made to enter the Pentose Phoshate pathway?

A

NO!

Pyruvate can only enter the following pathways:

1) acetyl-CoA → citric acid cycle
2) oxaloacetate → TCA cycle or gluconeogenesis
3) alanine → glucose-alanine cycle
4) lactate → Cori cycle (hepatic gluconeogenesis from lactate)

50
Q

Overall, how many ATP are consumed for each round of the Cori cycle? What is the result?

A

4 net ATP.

therefore, there is a metabolic shift to the liver.

51
Q

Glycolysis and anaerobic metabolism in the muscle cells generate 2 ATP per glucose; gluconeogenesis in the liver consumes ___ ATP to generate one glucose from two lactate.

A

6 ATP

52
Q

Glucose-6-phosphatase catalyzes this reaction, which occurs in the _______________ of the cell. The sequestration of this enzyme assures it does not compete with glucokinase/hexokinase during glycolysis.

A

smooth endoplasmic reticulum

53
Q

What inhibit fructose-1,6-bisphosphatase? (2)

A

Fructose-2,6-bisphosphate and AMP

54
Q

As the rate-limiting step of gluconeogenesis, fructose-1,6-bisphosphatase has many allosteric activators and inhibitors. What are the activators?

A

Citrate, ATP, and acetyl-CoA allosterically activate fructose-1,6-bisphosphatase, as they are indicative of a heavily glycolytic environment.

55
Q

What is the RDS reaction in Gluconeogenesis?

A

The conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.

catalyzed by fructose-1,6-bisphosphatase.

56
Q

___________ is transported to the cytosol using the malate shuttle.

A

Oxaloacetate

57
Q

The 2nd reaction of gluconeogenesis: Oxaloacetate → Phosphoenolpyruvate (PEP).

What enzyme catalyzes this reaction?

A

PEP carboxykinase catalyzes this reaction, which occurs in the cytosol.

58
Q

excess __________ is indicative of a need for a shift from glycolysis to gluconeogenesis.

A

acetyl-CoA

59
Q

__________ is a cofactor of the pyruvate → oxaloacetate reaction catalyzed by pyruvate carboxylase.

A

Biotin

60
Q

The 1st reaction of gluconeogenesis: Pyruvate → Oxaloacetate.

What enzyme catalyzes this reaction?

A

Pyruvate carboxylase catalyzes this reaction, which occurs in the mitochondria.

61
Q

What metabolites has an entry point that is the furthest upstream among the non-pyruvate substrates?

A

All triacylglycerides (TAGs) can be metabolized to form glycerol, which can enter gluconeogenesis through several reactions resulting in the formation of DHAP.

62
Q

What non-pyruvate substrae enters gluconeogenesis thru multi-step conversion to OAA?

A

Metabolites of fatty Acid Metabolism enter Gluconeogenesis as PROPIONYL-CoA

ODD-number fatty acids only! even-chain fatty acids do not produce propionyl-CoA.

63
Q

What two carbon substrates can enter gluconeogenesis thru DIRECT conversion to PYRUVATE?

A

Alanine & Lactate

64
Q

What step in gluconeogenesis is 2 GTP per glucose consumed?

A

OAA –> PEP

via PEP caroxykinease

65
Q

Where is the cell does Pyruvate Carboxylase work?

A

Mitochondria:

Pyruvate –> OAA

66
Q

Where is the cell does G6P dephosphorylation occur?

A

Smooth ER

67
Q

Muscle cells cannot raise blood glucose via gluconeogenesis because they lack ____________. Because phosphorylated glucose is unable to exit the cell, glucose remains trapped in the myocytes.

A

glucose-6-phosphatase

68
Q

What substrates inhibit fructose-1,6-bisphosphatase? (2)

A

Fructose-2,6-bisphosphate

&

AMP

69
Q

What stimulates Pyruvate Carboxylase to convert pyruvate to OAA?

A

acetyl-CoA

70
Q

In gluconeogenesis:

Fructose-1,6-bisphosphate → Fructose-6-phosphate

is catalyzed by what enzyme?

A

Fructose-1,6-bisphosphatase;

occurs in the cytosol.

71
Q

In glycogen, the linear bonds are ___________ linkages whereas the branching bonds are __________ linkages.

A

Linear bonds: α-(1,4) glycosidic

Branching bonds: α-(1,6) glycosidic

72
Q

Glycogen is synthesized and stored primarily where?

A

in the cytoplasm of hepatocytes and skeletal muscle cells.

73
Q

__________ is a highly branched (branching every ~10 glucosyl residues) glucose polymer used as the main storage form of glucose in the body.

A

Glycogen

74
Q

The first step in glycogenesis is:

Glucose + 1 ATP → Glucose-6-Phosphate + ADP

This reaction requires what cofactor?

A

magnesium

75
Q

What is the second step of glycogensis?

What is the enzyme involved?

A

glucose-6-phosphate is isomerized (“mutated”) to glucose-1-phosphate in a reversible reaction.

phosphoglucomutase

76
Q

What is phosphoglucomutase?

A

The enzyme that isomerizes (“mutates”) glucose-6-phosphate to glucose-1-phosphate.

77
Q

What is he third step of glycogenesis?

What is the enzyme involved?

A

glucose-1-phosphate + UTP → UDP-glucose + 2Pi

glucose-1-phosphate uridylyltransferase (aka UDP-glucose pyrophosphorylase)

78
Q

What is the RDS rxn in glycogen synthesis?

A

the addition of UDP-glucose to a pre-existing glycogen chain via a α(1,4)-glycosidic linkage.

79
Q

The enzyme that catalyzes the addition of UDP-glucose to an existing glycogen molecule is ____________.

A

glycogen synthase

80
Q

glycogen synthase is activated by:

glycogen synthase is inhibited by:

A

glycogen synthase is activated by: insulin and glucose.

glycogen synthase is inhibited by: Glucagon and epinephrine

81
Q

Branching enzyme makes branch points in a linear glycogen molecule using α-(1,6) glycosidic bonds, about every ____________.. What does this allow for?

A

10 glucosyl residues.

allows for more compact storage of a greater number of glucose molecules.

82
Q

What is the enzyme that catalyzes the rate-determining step of glycogenolysis?

A

glycogen phosphorylase.

83
Q

What enzyme removes the phosphate from glucose-6-phosphate to create free glucose?

A

Glucose 6-phosphatase

84
Q

What is the possible fates of glucose-6-phosphate? (3)

A
  • Glycolysis
  • Pentose phospahte pathway (aka hexose monophosphate shunt)
  • converted to free glucose in the liver.
85
Q

What provides the energy for creating the proton gradient in the electron transport chain?

A

the flow from (e-), provided from NADH and FADH2, thru the ETC provide the energy to pump protons into the INNER MITOCHONDRIAL inter-membrane space to create the E-C proton gradiant

86
Q

What is thermogenin w.r.t. the ETC?

A

Thermogenin in brown fat is an uncoupling agent that disrupts the proton gradient. This is physiologically used to generate heat in infants, who possess brown fat.

87
Q

What are the two shuttles used to transport NADH across the inner mitochondrial membrane?

Which one is more energy efficient?

A
  1. Malate-aspartate shuttle; more efficient!

2. G3P shuttle

88
Q

Complex II is also what same enzyme of the citric acid cycle?

A

succinate dehydrogenase

89
Q

What is Complex V of the ETC also known as? What powers this complex?

A

ATP Synthase (Complex V): uses the electrochemical proton gradient created by the ETC to produce ATP from ADP and Pi.

90
Q

As a toxin, what enzyme in the ETC does Carbon Monoxide bind to?

A

Cytochrome C Oxidase.

CN (Cyanide) also binds to this enzyme.

both consume O2 and deprives the mitochondria of its final (e-) acceptor.

91
Q

Which toxin of the ETC binds to and inhibits ATP synthase?

A

Oligomycin

92
Q

Which toxin transports protons across the mitochondrial membrane, inhibiting the electron transport system?

A

2,4-DiNitroPhenol

93
Q

2,4-Dinitrophenol and increased doses of aspirin increase the permeability of the inner mitochondrial membrane leading to a _____1_____ proton gradient and _____2_____ oxygen consumption. Heat is generated instead of ATP (this explains the fever generated following toxic doses of aspirin.)

A
  1. decreased proton gradient

2. increased O2 consumption

94
Q

What are the mobile (e-) carriers of the ETC?

A

Coenzyme Q & Cytochrome C

DEMS_BTRAN (8 decks)

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