Glycolysis, pyruvate oxidation, Krebs cycle Flashcards

Question 1

Q

What is the function of glycolysis?

Phases?

Where does it happen?

Answer

A

1 molecule of glucose is converted to 2 molecules of pyruvate, in 3 phases - 10 steps:

energy investment: 3 steps
cleavage of C6 sugar to 2 C3 sugars: 2 steps
energy generation: 5 steps

happens in cytosol

Question 2

Q

What are the 2 net equations of glyclosis?

Why plural?

Answer

A

can happen either under aerobic or anaerobic conditions

aerobic: cf. image
anaerobic: 2 NAD⁺ → 2 NADH/H⁺ less
(→ NADH⁺ used to produce lactate)

Question 3

Q

What would reasons for anaerobic conditions be?

Examples.

Answer

A

hypoxia/anoxia due to resp./circ. pathologic conditions, asphyxia, poisons
relative hypoxia due to extreme O₂ consumption, e.g. during exercise
lack of mitochondria, e.g. in RBCs (→ always anaerobic)

Question 4

Q

What is the 1^st step of glycolysis?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

hexokinase/glucokinase
1^st ATP used

glucose + ATP → glucose-6P + ADP

IRREVERSIBLE, inhibited allosterically by product

_{part of energy generation phase}

Question 5

Q

What is the difference btw hexo- and glucokinase?

Effects?

Answer

A

hexokinase: low K_m for glucose, always active
glucokinase: high K_m, active after meal to remove glucose from hepatic portal blood
- in liver → energy
- in pancreatic β-cells → detect [glucose], triggers insulin release

Question 6

Q

What happens to G6P?

Catalyzed by.. ?

Structures.

Answer

A

phosphohexose isomerase
isomerizes aldose to ketose

glucose-6P ⇔ fructuose-6P

Question 7

Q

What happens to F6P?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

phosphofructokinase 1
2^nd ATP used

F6P + ATP → fructose 1-6-bisphosphate

IRREVERSIBLE, rate-limiting step of glycolysis

Question 8

Q

What happens to F1,6BP?

Catalyzed by.. ?

Structures.

Answer

A

aldose A
cleaves F1,6BP into 2 trioses

F-1,6-BP → G3P + DHAP

NOTE: only G3P can proceed immediately through glycolysis

Question 9

Q

What happens to DHAP?

Catalyzed by.. ?

Structures.

Answer

A

phosphotriose isomerase

DHAP ⇔ G3P

necessary b/c DHAP cannot proceed further in glycolysis w/o isomerization → after this step: 2 G3P

Question 10

Q

What happens to G3P?

Catalyzed by.. ?

Structures.

Answer

A

glyceraldehyde 3-P dehydrogenase
anhydride bond formed

G3P + NAD⁺ + P_i → 1,3BPG + NADH

Question 11

Q

Which substance is an inhibitor of glyceraldehyde 3P dehydrogenase?

Answer

A

iodoacetate can bind to -SH groups, causing inhibition

Question 12

Q

What happens to 1,3BPG?

Catalyzed by.. ?

Structures.

Answer

A

phosphoglycerate kinase

1,3-BPG + ADP ⇔ 3-phosphoglycerate + ATP

1^st substrate level phosphorylation

Question 13

Q

1,3BPG can normally be used for glycolysis in erythrocytes or… ?

Catalyzed by?

Name the enzyme catalyzing the reverse reaction, too.

Answer

A

bisphosphoglycerate mutase

1,3BPG ⇔ 2,3BPG
(instead of synthesis of 3-phosphoglycerate)

BUT: can be converted to 3-phosphogylcerate by 2,3-BPG phosphatase (w/o ATP yield)

Question 14

Q

Why is arsenic toxic and lethal?

Answer

A

analogue of P_i→ energy in ester/anhydride bonds lost

⇒ uncoupling oxidation and phosphorylation in glycolysis

Question 15

Q

What happens to 3-phosphoglycerate?

Catalyzed by.. ?

Structures.

Answer

A

phosphoglycerate mutase
moves position of ester bond

3-phosphoglycerate ⇔ 2-phosphoglycerate

Question 16

Q

What happens to 2-phosphoglycerate?

Catalyzed by.. ?

Structures.

Answer

A

enolase
dehydration to form enol (macroergic bond)

2-PG ⇔ PEP + H₂O

Question 17

Q

What compounds act as cofactor for enolase?

Answer

A

Mg²⁺, Mn²⁺

Question 18

Q

Which substance can inhibit enolase?

Answer

A

fluoride

Question 19

Q

What happens to PEP?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

pyruvate kinase

PEP + APD → pyruvate + ATP

2^nd substrate level phosphorylation

+ irreversible b/c pyruvate isomerizes from high E enol into keto-form

Question 20

Q

What are possible pathways of the 2 molecules of pyruvate produced in glycolysis?

Answer

A

under aerobic conditions: enter PDC, are converted to 2 acetyl-CoA, 2 CO₂ released
under anaerobic conditions: LDH converts both pyruvate to 2 lactate, 2 NADH consumed

Question 21

Q

What is the function of the pyruvate dehydrogenase complex (PDC)?

Where does it happen?

Answer

A

oxidative decarboxylation: pyruvate → acetyl-CoA

happens in mitochondrial matrix
irreversible

(requires O₂ = only aerobic, releases CO₂)

Question 22

Q

What is the net equation of the reaction catalyzed by PDC?

Answer

A

pyruvate + NAD⁺ + CoA-SH

↓

acetyl-CoA + NADH/H⁺ + CO₂

Question 23

Q

Describe the structure of the PDC, listing subunits, and their prosthetic groups.

Answer

A

3 subunits:

E₁: pyruvate dehydrogenase (TPP = prost. group)
E₂: dihydrolipoyl transacetylase (lipoic acid = prost. group)
E₃: dihydrolipoyl dehydrogenase (FAD = prost. group)

_{TPP (thiamine pyrophosphate) and TDP (diphosphate) are same thing}

Question 24

Q

Which substances act as coenzymes during oxidative carboxylation of pyruvate?

Answer

A

NAD⁺ and CoA-SH

Question 25

Q

Which reaction is catalyzed by E₁ of the PDC?

Name of enzyme.

Structures.

Answer

A

pyruvate dehydrogenase
oxidative phosphorylation

pyruvate + TPP → hydroxyethyl-TPP + CO₂

_{TPP (thiamine pyrophosphate) and TDP (diphosphate) are same thing}

Question 26

Q

What is another name for thiamin?

What are possible consequences of a thiamin deficiency?

Why?

Answer

A

vitamin B₁

deficiency can be caused by alcoholism (poor diet + reduced thiamin absorption)
leads to impaired glucose metabolism, possible life-threatening lactic/pyruvic acidosis

(bc part of TPP)

Question 27

Q

What is the first reaction catalyzed by E₂ of the PDC?

Name of enzyme

Structures.

Answer

A

dihydrolipoyl transacetylase

oxidized lipoamide + hydroxyethyl-TPP
→ acetyl-lipoamide + TPP

_{TPP (thiamine pyrophosphate) and TDP (diphosphate) are same thing}

Question 28

Q

What is the second reaction catalyzed by E₂ of the PDC?

Name of enzyme.

Structures.

Answer

A

dihydrolipoyl transacetylase

acetyl dihydrolipoamide + CoA-SH
→ dihydrolipoamide + acetyl-CoA

_{TPP (thiamine pyrophosphate) and TDP (diphosphate) are same thing}

Question 29

Q

Which reaction is catalyzed by E₃ of the PDC?

Name of enzyme

Structures.

Answer

A

dihydrolipoyl dehydrogenase

dihydrolipoamide + FAD
→ oxidized lipoamide + FADH₂

→ then transferred to NAD⁺ → NADH formed

Question 30

Q

How do you call the high energy bond in acetyl-CoA?

Answer

A

thioester

Question 31

Q

As a summary…

List the products of each step of the oxidation of pyruvate.

Answer

A

pyruvate converted to

E₁ → hydroxyethyl-TPP + CO₂
E₂ (step 1) → acetyl-dihydrolipoamide + TPP
E₂ (step 2) → dihydrolipoamide + acetyl-CoA
E₃ → oxidized lipoamide + NADH/H⁺ + FAD

⇒ overall: acetyl-CoA + CO₂ + NADH/H⁺

Question 32

Q

What are the 2 mechanisms of regulation of the PD complex?

Answer

A

allosteric inhibition: E₂ and E₃ subunits
de-/phosphorylation: of E₁ subunit by PDC kinase and phosphatase

Question 33

Q

Which subunits of PDC are allosterically inhibited?

By which substances?

Answer

A

product inhibition

E₂ inhibited by: acetyl-CoA
E₃ inhibited by: NADH

Question 34

Q

Which subunit of PDC is regulated by de-/phosphorylation?

By which substances?

Answer

A

E₁ either

phosphorylated = inhibited by PDC kinase

lot of energy: ATP, NADH
product: acetyl-CoA

dephosphorylated = activated by PDC phosphatase

insulin
exercise: Ca²⁺, Mg²⁺

Question 35

Q

What does dichloroacetate do?

Answer

A

inhibits PDC kinase → no phosphorylation, PDC active

Question 36

Q

Which molecules serve as substrate of the Krebs cycle, what are the final products?

Where does it happen?

Aerobic or anaerobic?

Answer

A

oxidation: acetyl-CoA → 2 CO₂

⇒ 1 ATP equiv., 1 FADH₂, 3 NADH produced, used for ox. phosphorylation

happens in mitochondrial matrix
only in aerobic conditions

8 steps

Question 37

Q

What is anaplerosis?

Answer

A

ex: intermediates in Krebs cycle

intermediates are all resynthesized, not consumed

Question 38

Q

What happens to acetyl-CoA (first step of the Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

citrate synthase
via intermediate

acetyl-CoA + OXA + H₂O → citrate + CoA-SH

irreversible b/c thioester bond of acetyl-CoA cleaved

Question 39

Q

What happens to citrate (second step of the Krebs cycle)?

Catalyzed by.. ?

This is the reason why… ?

Structures.

Answer

A

aconitase
citrate dehydrated to intermediate, eventually isomerized to isocitrate

citrate ⇔ H₂O + cis-aconitate ⇔ isocitrate

⇒ reason why first CO₂s lost, not carbon atoms of acetyl-CoA (but OXA..?)

Question 40

Q

Which substance can inhibit the aconitase?

Answer

A

thoroacetate

Question 41

Q

What happens to iscitrate (third step of the Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

isocitrate dehydrogenase

isocitrate + NAD⁺ → CO₂ + NADH + α-KG

1^st oxidative decarboxylation
irreversible

Question 42

Q

What is the cofactor of isocitrate DEH?

Answer

A

Mg²⁺/Mn²⁺

Question 43

Q

What happens to α-KG (fourth step of the Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

α-ketoglutarate dehydrogenase complex

α-KG + CoA-SH + NAD⁺
→ CO₂ + NADH + succinyl-CoA

2^nd oxidative decarboxylation
irreversible

similar to PDC, same E₃ subunit, uses same cofactors

Question 44

Q

Which substance/condition inhibit the α-ketoglutarate dehydrogenase complex?

Answer

A

arsenite
hyperammonemia

Question 45

Q

What happens to succinyl-CoA (fifth step of Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

succinyl-CoA synthetase

succinyl-CoA + H₂O + GDP + P_i
⇔ succinate + GTP + CoA-SH

substrate-level phosphorylation
in gluconeogenic tissues (liver/kidney) ATP can be formed instead of GTP

Question 46

Q

What happens to succinate (sixth step of Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

succinate dehydrogenase

succinate + FAD ⇔ FADH₂ + fumarate

on inner mit. membrane (complex II), e^- from FADH transferred via Fe-S centers to CoQ

Question 47

Q

Which substance inhibits succinate dehydrogenase?

Answer

A

malonate binds competitively to succinate dehydrogenase

Question 48

Q

What happens to fumarate (7th step of Krebs cycle)?

Catalyzed by.. ?

Structures.

Answer

A

fumarase

fumarate + H₂O ⇔ L-malate

Question 49

Q

What happens to malate (8th step of Krebs cycle)?

Catalyzed by.. ?

Anything important?

Structures.

Answer

A

malate dehydrogenase

malate + NAD⁺ → OXA + NADH

BUT: high [reagents] strongly shift equlibrium to the right (favoring products, irreversible)

_{NOTE: equilibrium inversed in case of gluconeogenesis}

Question 50

Q

How is the activity of the Krebs cycle regulated?

Answer

A

happens only in aerobic conditions, activated by

low [NADH], [ATP]
low [succinyl-CoA]
Ca²⁺ = e.g. during exercise

Question 51

Q

Which vitamins act as coactivators, being essential in the Krebs cycle?

Answer

A

4 B vitamins

riboflavin: in form of FAD
niacin: in form of NAD⁺
thiamin: as TPP, part of α-ketoglutarate dehydrogenase complex
pantothenic acid: part of CoA

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Glycolysis, pyruvate oxidation, Krebs cycle Flashcards

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