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Biochemistry > Glycolysis/TCA > Flashcards

Glycolysis/TCA Flashcards

1
Q

What are the three dietary macronutrients? What is the largest portion ingested during a meal?

A

Carbs,protein,fat

Carbs

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2
Q

What is glycolysis ?

A

Glucose to Pyruvate conversion

Funnels Fuel Molecules to the TCA

Provides energy as ATP

Provides substrates for biosynthetic reactions, fatty acids and some amino acids

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3
Q

What are the net products per glucose molecule of pyruvate?

A

2ATP , 2 NADH , 2 Pyruvate

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4
Q

Every cell in the body can do glycolysis. True or false?

A

True

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5
Q

Glycolysis is the sole source of ATP in some cells. True or False

A

True

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6
Q

The only pathway that can produce ATP is anaerobically is ____________.

A

Glycolysis

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7
Q

Glycolysis occurs in the ________.

A

Cytoplasm

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8
Q

Describe general steps Glycolysis

A

The oxidation of glucose to 2 triose pyruvate provides electrons for the reduction of 2NAD+ to make 2NADH and 2 ATP.

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9
Q

When ____ is low, glycolysis can’t occur. _____ must be recycled back into ______.

The _____ can act as a ______ to regenerate _______.

A

NAD+, NADH, NAD+

ETC, electron sink, NAD+

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10
Q

After conversion into pyruvate, what must happen in order for the molecule to enter the TCA cycle?

Where do NADH and pyruvate need to go in order for this to happen?

A

Pyruvate must be made into Acetyl-CoA.

NADH and pyruvate must be transported to the mitochondria.

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11
Q

Under aerobic conditions what 3 things happen after glycolysis?

A
  1. ETC acts as an electron sink to regenerate NAD+
  2. Pyruvate can be converted to AcetylCoA to enter TCA
  3. NADH and Pyruvate must be carried to mitochondria
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12
Q

How much ATP does the TCA and Oxidative Phosphorylation generate?

A

34-36 ATP

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13
Q

Under anaerobic conditions, what process are unable to occur? What happens as a result?

A

NO TCA or Oxidative Phosphorylation

NADH and pyruvate accumulate (1:1) BUT there is a process to regenerate NADH via Lactic Acid Fermentation.

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14
Q

What is used as the electron sink in lactic acid fermentation since the ETC is unavailable?

A

Pyruvate reduction into lactate allows NADH to be oxidized into NAD+. This allows glycolysis to continue.

LACTATE IS IMPORTANT

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15
Q

There are two phases in glycolysis. What are they and what happens in them?

A

Preparative Phase that consumes ATP

Glucose consumes 2 ATP to become Fructose 1,6 Bisphosphate. There is a phosphate at either end of this molecules (1,6)

ATP-Generating Phase

Fructose 1,6 Bisphosphate becomes 2 Triose phosphates. Each triose phosphate generate 1 ATP via substrate level phosphorylation and 1 reduction of NAD+ to NADH. In the formation of each triose to 1 pyruvate another ATP is released yielding 1 NADH and 2 ATP release PER pyruvate molecule

1 NADH and 2 ATP release PER pyruvate molecule

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16
Q

What are the two irreversible steps in glycolysis?

What is the major regulatory one?

A
  1. Hexokinase (D-Glucose to Glucose -6-phosphate)
  2. Phosphofructokinase-1 ( Fructose-6-phosphate to Fructose 1,6 bisphosphate)

PFK-1 is regulatory

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17
Q

What is the first irreversible step in glycolysis and what does it do?

A

Hexokinase phosphorylates the 6 position of glucose. By (negatively) ionically charging it, the glucose is now unable to cross the plasma membrane into the blood. It is locked into the cell.

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18
Q

What is the major regulation step in glycolysis and why is it important?

A

PFK-1 phosphorylates the 1 position of Fructose-6-Phosphate (intermediate after Glucose-6-Phosphate) to make Fructose 1,6 Bisphosphate.

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19
Q

What is the hexokinase of the liver?

A

Glucokinase

Also found in beta cells of pancreas

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20
Q

Aside from glycolysis, what other fate does glucose have in the pathway?

A

Glycolysis
Pentose Phosphate pathway to make nucleotides and NADPH
Glycogen Synthesis

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21
Q

What does the Pentose Phosphate Pathway create?

A

Nucleotides and NADPH

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22
Q

Hexokinase has a _______ affinity for both _____ and _______ and is controlled by _________.

A

high , substrate and product,

product inhibition

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23
Q

Glucokinase has _________ affinity for both ______ and is controlled by _______.

A

low , substrate and product,

cellular localization and substrate availability

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24
Q

Since glucokinase has _____ affinity, its Km is _______ and it has a _____ curve.

Hexokinase has _____ affinity, its Km is _______ and it has a _____ curve

A

low, high, sigmoid

high, low, standard

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25
Q

Hexokinase is in ______ cells.

A

ALL

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26
Q

Why does glucokinase have low affinity?

A

The liver is meant for storing EXTRA glucose. So when glucose reaches a pretty high level, glucokinase will work more.

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27
Q

What inhibits hexokinase?

A

Glucose-6-phosphate

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28
Q

What is the most potent Hexokinase? Why?

A

II Both of its catalytic domains are active.

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29
Q

How many catalytic domains does glucokinase have?

A

1

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30
Q

Hexokinase _____ and ____ have a _____ that localizes them to the ____.

A

1 and 2, motif, mitochondria

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31
Q

What tissue is the biggest user of glucose?

A

Brain

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32
Q

Hexokinase 1 and 3 are co-expressed with __________

A

GLUT 1,3,4

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33
Q

Glucokinase is co-expressed with _______.

A

GLUT 2

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34
Q

Activity of _______ increases with rising glucose concentration since it has a high Km.

A

glucokinase

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35
Q

In the absence of glucose, glucokinase is sequestered to the _____.

A

Nucleus

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36
Q

After separation of the trioses __________ is oxidized to allow the reduction of _______.

Increasing the ___ state of the molecules increases the ______.

A

Glyceraldehyde , NAD+ to NADH

oxidative state, energy of bonds as ATP

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37
Q

Where does actual ATP come from in glycolysis?

A

Substrate level phosphorylation of the glyceraldehyde after oxidation into 1,3 bisphospho glycerate (ADP to ATP)

Substrate level phosphorylation of Phosphenol pyruvate to pyruvate (ADP to ATP)

BIG PICTURE: Glyceraldehyde triose gets oxidizes once to 1,3 Bisphosphoglycerate and also created NADH. After, the intermediets that follow go through 2 rounds of substrate level phosphorylation to create pyruvate and phosphorylate two ADP molecules to two ATP PER triose phosphate molecule.

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38
Q

Order the following by high ATP yielded.

Carboxylic Acid, Alcohol, Aldehyde/Ketone

A

Alcohol
Aldehyde/Ketone
Carboxylic Acid

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39
Q

What exactly occurs in anaerobic glycolysis?

A

Glyceraldehyde is reduced to lactic acid to oxidize NADH back to NAD+.

2 ATPs are generated

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40
Q

Hereditary deficiencies of glycolytic enzymes lead to _________ because.

A

hemolytic anemia, insufficient ATP to maintain Na+/K+ gradient across red blood cell membrane

RBCs are VERY dependent because RBCs can only do glycolysis.

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41
Q

Most common glycolytic mutations occur at _______.

What is the absolute most common?

A

Hexokinase activity, PFK-1, Pyruvate Kinase

Pyruvate Kinase substrate level phosphorylation of ATP from creation of Pyruvate.

42
Q

Why are RBCs dependent on glycolysis?

A

They have no mitochondria. Lack of ATP can lyse cells due to be unable to maintain the electrochemical gradient.

43
Q

How does NADH/NAD+ get across the mitochondrial membrane from the cytoplasm during aerobic glycolysis?

A

The glycersol shuttle or the malate aspartate shuttle.

44
Q

Anaerobic Glycolysis uses ______ to reduce 2 _______ to ______ to create ___________.

A

lactate dehydrogenase, pyruvate, lactate, 2 NADH and 2 ATP

45
Q

What cells only do anerobic glycolysis and why?

A

RBC - No mitochondria

Lens and cornea of Eye- NO mitochondria and no capillaries

Skin - Produces lactic acid as antibacterial mechanism

Large Tumors - Poor vascularization , low O2

Skeletal Muscle during Intense Exercise - Energy production is trying to keep up with consumption, can take up O2 from circulation

46
Q

What is lactic acidosis and what is it caused by?

A

Intense exercise, heart attack ,severe anemia, large tumors (All are hypoxic)

Lots of lactate can low pH of blood because of carboxylic acid group present

47
Q

_____ and _____ can convert lactate from the blood to ________. The ______ can also convert it back into ______ to return to cells/tissues for energy.

A

Heart and Muscle, pyruvate

liver, glucose (gluconeogenesis)

48
Q

Dental Applications

Biofilms are in an ______ state. As microbiota undergo __________, they will release ________ which is_______.

A

anaerobic

glycolysis, lactate, dangerous for enamel

49
Q

Flouride is ______ because it inhibits _________. This is a key _____ for ________in _______.

A

anticariogenic, enolase enzyme

enzyme, preventing glycolysis (lactate) by preventing production of pyruvate, oral bacteria

50
Q

Muscle regulates glycolysis by ___________.

A

Energy needs of the cell (ATP)

51
Q

Liver regulates glycolysis by ____________.

A

Dual function ; Energy needs (ATP) and nutritional status

  1. Provide energy from glucose metabolism
  2. Convert excess glucose to fatty acids for storage

ONLY in fed state

52
Q

What is one of the most highly regulated enzymes? How is it regulated?

A

PFK-1 - Allosteric

  1. Fructose2,6 Bisphosphate - Activator
  2. AMP - Activator (Muscle)
  3. ATP, Citrate - Inhibitor
53
Q

How down F-2,6-BP _____ PFK1?

A

Activate

PFK-2 phosphorylate Fructose 6-phosphate at the 2 postition to make F-2,6-BP. When levels fall, glycolysis in inhibited and directed to gluconeogenesis.

Regulated by insulin.

54
Q

PFK-1 Kinetics

ATP binds to _______.

AMP _____ ATP binding to the ___________ overcoming its ___.

AMP facilitates _______ of ______________.

A

two sites ( substrate binding and allosteric inhibitory)

Since ATP has high affinity for the sight, F6P binding is lower.

AMP blocks ATP binding to the allosteric site overcoming its inhibition.

AMP facilitate binding of F-6-Phosphate.

55
Q

Why is AMP necessary?

At rest, AMP change is ___ high.

A

It is in equilibrium with ATP and ADP in the cell at all times because of ADENYLATE KINASE. It is a sensitive indicator of cellular energy depletion

2 ADP < —– (Adenylate kinase) ——–> AMP + ATP

At rest, AMP change is VERY high.

56
Q

Why does pyruvate need to be converted to acertyl CoA

A

Pyruvate Dehydrogenase, a mitochondrial matrix protein, must convert it to allow it to enter the TCA

57
Q

PDH is activated by _______and _________ by as well as regulated by ________.

A

Substrates, Products

Phosphorylation Status

When Ca2+ is high, phosphatase makes PDH active

When ADP is low, Pyruvate is low OR Acetyl CoA and NADH are high, kinase will activate PDH

58
Q

Why can you never make glucose out of fatty acids?

A

Acetyl CoA CANNOT be converted back to pyruvate

59
Q

What is cellular respiration?

A

Process that releases energy by breaking down food in the presence of O2 to make ATP.

Sugar + Oxygen —– . CO2 + Water + ATP

60
Q

What two process are key for cellular respiration?

A

TCA and Oxidative Phophorylation

61
Q

What are the three important high energy compounds?

A

ATP , Acetyl CoA, Succinyl CoA

62
Q

Why is ATP the preferred high energy compound?

A
  1. Energy is readily available
  2. Quick and Renewable
  3. Responds to energy demands
63
Q

What is the structure of ATP?

A

Ribose sugar with a Adenine on 1’ carbon and triphosphate chain on 5’.

64
Q

In ATP, there are _________bonds between the phosphate groups and _____bonds between the proximal phosphate group and the 5’ carbon.

A

2 Phosphoanhydride bonds

1 Ester Bond

65
Q

What are the 4 significant factors regarding the TCA cycle?

A

Supplies Energy as Electron Carriers for synthesis of ATP

Central Metabolic Pathway in Oxidation of Fuels (Integration point)

Provides metabolic intermediates for synthesis of several molecules like AAs, glucose

Part of complex process where cells can turn food into energy as NADH and FADH2

66
Q

What are the roles of oxidative phosphorylation?

A
  1. Transfer of electrons
  2. Energy is conserved by redox reactions which transfer electrons to NAD+ and FAD initially
  3. NADH and FADH2 release energy as they pass electrons to O2 in the ETC.
  4. NADH and FADH2 release energy for active transport of H+ across IMM
  5. H+ gradient helps drive ATP synthesis by running an ATP-drive H+ transporter back into the IMM.
67
Q

TCA(_____) occurs in ______

ETC and Oxidative Phosphorylation occurs in ________.

A

Krebs, Mitochondrial Matrix

ETC and Oxypho - Inner Mitochondrial Membrane

68
Q

What triggers the TCA cycle?

A

Acetyl-CoA from pyruvate

69
Q

As Acetyl-CoA is ________, electrons are taken up by ________.

A

oxidized, NAD+ and FAD+ to make NADH and FADH2 electron carriers

70
Q

How does pyruvate enter mitochondrial matric?

A

Mitchondrial Pyruvate Carrier

71
Q

Acetyl-CoA contains ____ reactions and _____ redox steps.

A

8 , 4

72
Q

What is the product of 1 AcetylCoA?

A

1 ATP
3NADH
1 FADH2
2 CO2

H2O + ATP (Waste)

73
Q

Where do electron carriers NADH and FADH2 go after TCA?

A

ETC

74
Q

What is coenzyme A ?

A

Acyl group

coenzyme A activates the transfer cofactor which transfers acyl units such as acetyl to molecules.

Hydrolyzes the thioester bond
EXERGONIC

Pyruvate + coenzyme A = Acetyl Co-A

75
Q

Which steps is CoA required in TCA?

A
  1. Formation of Citrate from Oxaloacetate
  2. Alpha-ketoglutarate to Succinyl CoA and NADH
  3. Succinyl CoA to Succinate

1- Delta G is negative
2. Delta G is negative
3. Substrate level phosphorylation

76
Q

When the ______ is cleaved in AcetylCoA or between any CoA bonded molecule in the TCA, it provides _____ to make the cycle run.

A

thioester, energy

77
Q

NAD+

What is it made of?
How does it make NADH

A

Nicotinamide base from Vitamin B3 (Niacin)
Adenine Dinucleotide

2 e- and 1 proton to make NADH
2nd proton is released as free NADH

78
Q

_____ can synthesize niacin needed for ___- from ______-.

A

Liver, niacin, tryptophan

79
Q

FAD

What is it made of?
How does it make FADH2

A

Flavin (Derived from riboflavin Vitamin B2)
Adenine dinucleotide

Accepts 2e- and 2H+ to make FADH2

80
Q

FAD is a ________ with a role in _____ and ____.

A

Prosthetic group (constantly bound to enzyme)

TCA, ETC

81
Q

The conversion of ________ to ________ the 4th biochemical reaction in TCA requires ____________.

A

alpha-ketoglutarate to Succinyl CoA

5 coenzymes, 3 enzymes, 4 vitamins

82
Q

B1 or ______ deficiency can cause ________ by ________ or ______.

A

Thiamine, beriberi

poor diet or chronic alcohol consumption

83
Q

TCA pathway is _________ or has a _________ delta G.

A

Exergonic , negative

84
Q

Acetyl CoA can only come from pyruvate. True or false

A

False

Pyruvate from glycolysis is preferred but fatty acid, ketone bodies, sugars, and Ethanol can all serve as precursors to Acetyl-CoA

85
Q

Why is alcohol not a good nutrient?

A

Inhibits absorption and usage of thiamin (B1) and B12

NO nutritional value

86
Q

The TCA is a _____ bolic pathway. What does this mean?

A

amphibolic

It does both breakdown and synthesis or molecules such as fatty acids, AAs, purine, glutamate, heme, pyrimidines, chlorophyll

AA, Cholesterol, Fatty Acids

87
Q

Which vitamins affect the TCA cycle the most?

A

Riboflavin
Niacin
Thiamin
Pantothenic Acid

88
Q

Niacin is associated with _______.

A

NAD+

89
Q

Riboflavin is associated with ______-

A

FAD

90
Q

Pantothenic Acid is associated with ______.

A

CoA

91
Q

Why is oxidative phosphorylation?

A

O2 is used to break down molecules and enzymes oxidize compounds to release chemical energy that produces ATP.

Oxidation of NADH to NAD+ and FADH2 to FAD using oxygen produces H2O

92
Q

Describe the pathway of electrons in the ETC.

A
  1. NADH will give up its electrons to Complex 1 while FADH will give up its electrons to Complex 2
  2. Co-enzymeQ collect e- from Complex I and II and transfers them to Complex III
  3. Cytochrome C will collect electrons from Complex III and transfer then to Complex IV.
93
Q

TCA cycle electrons enter the ETC. through _____________. How do fatty acid oxidation electrons enter?

A

Complex 1 and 2

FADH2

ETF-CoQ

94
Q

What is the role of NADH in Complex I ?

A
  1. Pass e- to O2 via ETC
  2. High ratio of NAD+/NADH drives fuel oxidation
95
Q

What is the role of FADH2 in Complex 2 ?

A
  1. Transfer e- to O2 via ETC
  2. Prosthetic group! So there are no pools of FAD/FADH2. In oxypho, e- from FADH2 are transferred to ubiquinone (oxidized CoQ) in the enzyme. Ubiquinol (reduced CoQ) can dissociate from the enzyme and contribute to the ubiquinone/ubiquinol pool in the IMM.
96
Q

Where is oxygen waiting ?

A

Complex IV

Oxygen is reduced to H2O and in the process, H+ is pumped to the intermembrane space.

97
Q

What is the chemiosmotic theory?

A

Transfer of e- through ETC leads to pumping of H+ to the inner mitochondrial membrane space. H+ is lower in matrix and an electric field with a negative matrix is generated.

This provide energy for synthesis of ATP via ATP synthase by coupling ADP and P

98
Q

If NADH/NAD is high, TCA will ______-

A

Slow down

Negative regulation; can inhibit enzyme activity

99
Q

If ATP/ADP is low, TCA will _______

A

Speed up

100
Q

What can inhibit the ETC and how?

A

No influx of H+ or e- transfer

Barbiturates
Antimycin A
Carbon Monoxide
Oligomycin

101
Q

Cyanide Poisoning

A

Chicago Tylenol Murders

Cyanide binds to one of the electron carriers in the Complex IV. This prevents oxygen from reaching any electrons because Complex IV is unable to receive any electrons.

Accumulation of NADH occurs and no ATP generation occurs

Biochemistry (18 decks)

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