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Block 1 > Metabolism > Flashcards

Metabolism Flashcards

1
Q

name the 3 GLUT transporters

A
  1. GLUT1: blood-brain barrier, erythrocytes
  2. GLUT2: liver, pancreas b-islet cells, small intestine
    - low affinity for glucose, bidirectional
  3. GLUT4: muscle, adipose (insulin-regulated)
    - exercise can induce expression
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2
Q

reaction and regulation of:

first irreversible step of glycolysis

A

glucose ==> glucose-6-phosphate
via hexokinase (muscle, adipose, RBC) or glucokinase (liver, pancreatic beta-cells)

hexokinase: not regulated by insulin, low Km and low Vmax
glucokinase: induced by insulin; inhibited by F6P and glucose; high Km and high Vmax

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3
Q

reaction and regulation of:

second irreversible step of glycolysis

rate-limiting step

A

fructose-6-phosphate ==> fructose 1,6-bisphosphate
via phosphofructokinase-1 (PFK-1)

inhibited by: ATP, citrate
activated by: AMP, fructose 2,6-bisphosphate

F2,6-bisphosphate is on/off switch for glycolysis

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4
Q

reaction and regulation of:

third (last) irreversible step of glycolysis

A

phosphoenolpyruvate (PEP) ==> pyruvate
via pyruvate kinase

inhibited by: ATP
activated by: AMP, fructose 1,6-bisphosphate

2 ATP generated

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5
Q

Cori cycle

A

glycolysis: glucose ==> pyruvate ==> lactate
gluconeogenesis: lactate ==> pyruvate ==> glucose
via lactate dehydrogenase

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6
Q

first irreversible reaction of gluconeogenesis

A

pyruvate ==> oxaloacetate
via pyruvate carboxylase

activated by: acetyl CoA (signals FA oxidation is taking place)

requires biotin as cofactor

this reaction also replenshes OAA for TCA cycle

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7
Q

second irreversible step of gluconeogenesis

A

oxaloacetate ==> phosphoenolpyruvate (PEP)
via phosphoenylpyruvate carboxykinase (PEPCK), rate-limiting step

cytosol (malate shuttle) and mitochondrial (lactate-pyruvate shuttle) PEPCK isozymes

inhibited by: insulin
activated by: glucagon

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8
Q

third irreversible step of gluconeogenesis

A

fructose-1,6-phosphate ==> fructose-6-phosphate
via fructose 1,6-bisphosphatase (FBP)

activated by: glucagon, low AMP, high ATP, low F26BP

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9
Q

fourth irreversible step of gluconeogenesis

A

glucose-6-phosphate ==> glucose
via glucose-6-phosphatase

only expressed in liver and kidney
inhibited by insulin
activated by glucagon

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10
Q

glycerol ==> glycerol-3-phosphate

product used in gluconeogenesis

A

catalyzed by glycerol kinase

hydrolysis of triacylglycerols ==> glycerol

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11
Q

other substrates for gluconeogenesis

besides pyruvate

A
  1. glycerol (TAGs hydrolysis)
  2. lactate (anaerobic glycolysis by muscle/RBCs)
  3. amino acids (glucogenic)
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12
Q

Cahill cycle

A

glucose-alanine cycle

liver: alanine ==> pyruvate ==> glucose
muscle: glucose ==> pyruvate ==> alanine

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13
Q

mechanism for:

alcoholic hypoglycemia

A

the metabolism of ethanol in the liver results in a massive increase in NADH

NADH drives pyruvate ==> lactate

by impairing the conversion of lactate to pyruvate, gluconeogenesis is impeded

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14
Q

irreversible step between glycolysis and TCA cycle

A

pyruvate ==> acetyl CoA
via pyruvate dehydrogenase complex (PDC)

deficiency in PDC causes lactate acidosis due to pyruvate being shunted to lactate; brain is particularly sensitive to acidosis

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15
Q

1st step of TCA cycle

irreversible step

A

acetyl CoA ==> citrate
via citrate synthase

citrate is an inhibitor of glycolysis
citrate can also be used for FA synthesis

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16
Q

2nd step of TCA cycle

reversible step

A

citrate ==> isocitrate
via aconitase

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17
Q

3rd step of TCA cycle

irreversible step

A

isocitrate ==> alpha-ketoglutarate
via isocitrate dehydrogenase

NAD+ ==> NADH

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18
Q

4th step of TCA cycle

irreversible step

A

alpha-ketoglutarate ==> succinyl CoA
via alpha-ketoglutarate dehydrogenase

NAD+ ==> NADH

19
Q

5th step of TCA cycle

reversible

A

succinyl CoA ==> succinate
via succinate thiokinase

GDP ==> GTP

20
Q

6th step of TCA cycle

reversible step

A

succinate ==> fumarate
via succinate dehydrogenase

FAD ==> FADH2

21
Q

7th step of TCA cycle

reversible step

A

fumarate ==> malate
via fumarase

22
Q

8th (final) step of TCA cycle

reversible step

A

malate ==> oxaloacetate
via malate dehydrogenase

NAD+ ==> NADH

23
Q

irreversible steps of TCA cycle

3 steps

A
  1. acetyl CoA ==> citrate, via citrate synthase
  2. isocitrate ==> alpha-ketoglutarate, via isocitrate dehydrogenase
  3. alpha-ketoglutarate ==> succinyl CoA, via a-ketogluarate dehydrogenase
24
Q

ATP-generating steps of TCA cycle

5 steps

A
  1. isocitrate dehydrogenase, NADH
  2. alpha-ketoglutarat dehydrogenase, NADH
  3. succinate thiokinase, GTP
  4. succinate dehydrogenase, FADH2
  5. malate dehydrogenase, NADH
25
Q

mechanism behind

glycogen synthesis

A

glucose-6-phosphate ==> glucose-1-phosphate ==> …

glycogenin catalyzes addition of first glucose
glycogen synthase adds subsequent glucose molecules, creating a(1->4) bonds
branching enzyme adds a(1->6) bond to create branches

26
Q

mechanism behind

glycogenolysis in lysosome

A

glycogen ==> glucose
via acid maltase (aka lysosomal a(1->4) glucosidase

where: heart, skeletal muscle, CNS

27
Q

mechanism behind

glycogenolysis in liver

A

glycogen ==> glucose-1-phosphate
via glycogen phosphorylase, which cleaves a(1->4) bond

4-C branch ==> glucose + glucose-1-phosphate
via debranching enzyme

glucose-6-phosphate ==> glucose
via glucose-6-phosphatase (also last step in gluconeogenesis)

28
Q

cellular locations of glycolysis, TCA cycle, gluconeogenesis, ETC

A

glycolysis: cytoplasm
TCA cycle: mitochondrial matrix
gluconeogenesis: cytoplasm
ETC: inner mitochondrial membrane

29
Q

ETC complex I

A

“NADH dehydrogenase”

NADH goes to complex I and gets oxidized to NAD+; 2e- goes to coenzyme Q (coenzyme Q gets reduced)

30
Q

ETC complex II

A

“succinate dehydrogenase”

FADH2 goes to complex II and gets oxidized to FAD; 2e- goes to coenzyme Q (coenzyme Q gets reduced)

31
Q

ETC complex III

A

“cytochrome bc1”; “coenzyme Q-cytochrome c reductase”

2e- from coenzyme Q transferred to cytochrome c (cyt c gets reduced);
4H+ transferred to intermembrane space

32
Q

ETC complex IV

A

“cytochrome c oxidase”

reduces O2 ==> H2O;
2H+ pumped into intermembrane space

33
Q

ETC complex V

A

“ATP synthase”

ADP + Pi ==> ATP

2.5 ATP per NADH;
1.5 ATP per FADH2

34
Q

Rotenone inhibits

A

ETC complex I (NADH dehydrogenase)

CoQ becomes oxidized

rotenone block can be bypassed by adding succinate

35
Q

Antimycin a inhibits

A

ETC complex III (coQ-cytc reductase)

Complex I becomes reduced, cytochrome c becomes oxidized

antimycin a block can be bypassed by adding ascorbate (vitamin C), which provides e- through cytochrome c

36
Q

Cyanide, CO, azide inhibit

A

ETC complex IV

all ETC components become reduced

37
Q

ETC/ox-phos uncouplers

A

aspirin, DNP (2,4-Dinitrophenol), brown fat (thermogenin)

reduced proton gradient and increased oxygen consumption → electron transfer continues but ATP synthesis stops → production of heat

38
Q

Oligomycin inhibits

A

ATP synthase

proton gradient becomes too steep for ETC to continue

39
Q

fatty acid activation

A

FA ==> fatty acyl CoA
via **fatty acyl CoA synthetase **

LC fatty acyl CoA transport into mitochondria for oxidation requires carnitine shuttle

VLC fatty acyl CoA synthetase only found in peroxisomes

40
Q

fatty acid beta-oxidation (even # chains)

A

fatty acyl CoA ==> acetyl CoA + remaining FA CoA chain (2 C less) + FADH2 + NADH

acetyl CoA goes to TCA cycle

41
Q

fatty acid beta-oxidation (odd # chains)

A

propionyl CoA (3-C chain) ==> 4-C chain ==> succinyl CoA
via propionyl CoA carboxylase

42
Q

fatty acid omega-oxidation

A

produces dicarboxylic cacids

occurs in endoplasmic reticulum

minor process that occurs more often when beta-oxidation is impeded

43
Q

branched chain fatty acid alpha-oxidation

A

ex: phytanic acid (plants)

propionyl CoA ==> succinyl CoA ==> TCA cycle

44
Q

ketone bodies

A

D-beta-hydroxybutyrate;
acetoacetate

ketone bodies ==> 2x acetyl CoA ==> TCA

Block 1 (10 decks)

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