Metabolism Flashcards

1
Q

Glucose utilization

A

(1) Storage: glycogen, starch, sucrose
(2) Oxidation: by glycolysis into pyruvate, by pentose phosphate pathway into ribose-5-P
(3) Structural polymers: can be used to make ECM and cell wall polysaccharides

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2
Q

Glucose source

  • 1 hr after meal
  • 4 h after meal
  • 2 days after meal
A
  • Dietary glucose
  • Glycogenolysis (glycogen runs out 12-14h after meal)
  • Gluconeogensis
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3
Q

Important enzymes for regulation of blood glucose after meal

A

In glycolysis:
Glucokinase (Glucose –> Glucose-6-P)
PFK1 (Fructose-6-P to Fructose-1,6-BP)
Pyruvate kinase (PEP –> Pyruvate)

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4
Q

Glycolysis nets:

A

2ATP, 2NADH, 2 Pyruvate

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5
Q

How does glucose get into cells?

A

Sodium independent transporters: GLUT1-GLUT14

Sodium cotransporter system (SGLT)

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6
Q

Hexokinase is found? Km/Vmax?

Glucokinase is found? Km/Vmax? Regulated by?

A

Hexokinase found in most cells. Low Km/Vmax

Glucokinase found in pancreatic beta cells. High Km/Vmax (allows pancreas to sense high levels of glucose). Regulated by glucokinase regulatory protein found in liver.

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7
Q

MODY Type 2

A

Maturity onset diabetes of young. Mutations of glucokinase causes it.

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8
Q

All carboxylases uses ___ as cofactor

A

Biotin

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9
Q

Fates of pyruvate

A

(1) Turned into OAA by pyruvate carboxylase
(2) Turned into lactate by lactate dehydrogenase (anaerobic)
(3) Turned into AcetylCoA by pyruvate dehydrogenase complex

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10
Q

Cori Cycle

A

Cycling of glucose and lactate between muscle and liver. In working muscle, Glucose –> pyruvate –> lactate; Lactate taken to liver and converted back to pyruvate before being transported back to muscle.

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11
Q

Pyruvate dehydrogenase

  • Does
  • Uses what as cofactor?
  • Active in what form?
A
  • Turns pyruvate into Acetyl CoA, release CO2.
  • Uses thiamine as cofactor. Thiamine deficiency increases lactate bc pyruvate DH can’t make acetyl CoA
  • Active when deppylated by PDH phosphatase (PDH kinase ppylates). PDH phophatase up-regulated by insulin and ADH.
  • Pyruvate and Ca2+ upregulate. ATP, acetyl CoA, NADH inhibit.
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12
Q

Glucose-6-phosphatase

  • Is expressed where?
  • Does what?
  • Defect leads to what?
A
  • Only expressed in liver and kidney ER.
  • Turns Glucose-6-P back into free glucose.
  • Von Gierke Disease –> can’t convert/generate free glucose. Large liver, short stature, low blood sugar. Increase gluconeogenesis, elevated lactate/acetyl CoA and alanine
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13
Q

What transports glucose out of cell

A

GLUT2

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14
Q

What regulates glucokinase?

A

Glucose +
Insulin +
Glucagon -
Fructose-6-P -

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15
Q

What regulates PFK-1?

A
Fructose-2,6-BP  +
Insulin  +
Glucagon  -
ATP -
Citrate -
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16
Q

What regulates pyruvate kinase?

A

F-1,6,-BP +
ATP - (by Mg2+ sequestration)
Glucagon - (by protein kinase A activation)
Alanine -

17
Q

Glycolysis mainly occurs in?

A

Muscles and brain

18
Q

Pentose phosphate shunt

A

Anaerobic non-ATP-production path that produces NADPH (useful for anabolism and resisting oxidative stress) and ribulose-5-phosphate (useful precursor for anabolic pathways).

Uses Glucose-6-P dehydrogenase (G6PD). NADPH downregulates G6PD, directing G6P to glycolysis if NADPH is too high.

19
Q

TCA Cycle produces?

A

3 NADH, 1 FADH2, 1 GTP (or ATP)

Each glucose runs TCA twice.

20
Q

ATP yield of breakdown of one glucose

A

Glycolysis: 2 ATP, 2 NADH = 5 or 7 ATP

Pyruvate oxidation: 1 NADH x 2 = 2 NADH = 5 ATP
TCA: (3 NADH, 1 FADH2, 1 GTP/ATP) x 2 = 6 NADH, 2 FADH2, 2 ATP = 15ATP + 3 ATP + 2 ATP = 20 ATP

Total = 30-32 ATP

21
Q

VDAC

A

Voltage dependent anionic channel (porin). Imports large anionic molecules into intermembrane space of mitochondria (but need a transporter to get into matrix)

22
Q

Mitochondria is divided into

A

(1) Outermembrane: protein transport
(2) Intermembrane space: electron transport chain; lower pH and more oxidizing than cytosol
(3) Inner membrane: oxidative ppylation
(4) Matrix: Krebs cycle

23
Q

Mitochondrial genome

A

Own circular genome, but only has 37 genes. Most mt genes are in the nuclear genome

24
Q

Cardiolipins

A

Embedded in inner mt membrane and stabilizes Complex IV of ETC

25
Q

ETC complexes reside where? What controls entrance?

A

In cristae (invaginations of inner membrane). Opa1 and MINOS (specialized proteins) control entrance to cristae.

26
Q

Translocation of mt proteins

A

Post-translational. Requires 5 protein complexes.

(1) TOM: translocates across outer membrane
(2) OXA: translocates matrix-made proteins into intermembrane space
(3) TIM23/PAM: translocates proteins into the matrix
(4) TIM22: facilitates folding of inner membrane proteins
(5) SAM: facilitates folding of beta-barrel outer membrane proteins

27
Q

What localizes mt proteins to the mt?

A

N-terminal sequences

28
Q

Hsp70

A

Facilitates folding in both cytosol and matrix. ATP hydrolysis is required to release proteins from Hsp70 for translocation

29
Q

What are used to thread membrane-spanning proteins into the mt membrane?

A

Stop-transfer sequences

30
Q

ER membrane and mt membrane

A

Are close to each other often. Lipids can translocate between the two.

31
Q

Mt matrix and cytoplasm potential

A

Mt matrix 80-150mV more negative than cytoplasm

32
Q

Mfn1

A

Involved in mt fusion

33
Q

Mfn2

A

Involved in mt fusion

34
Q

Opa1

A

Involved in mt fusion

35
Q

Drp1

A

Involved in mt fission

36
Q

Inhibition of entry in TCA cycle

A

Leads to buildup of pyruvate and lactate and depletion of glucose.

37
Q

CoQ (ubiquinone)

A

Carries electrons and protons across inner mt membrane to establish proton-motive force that drives oxidative phosphorylation of ADP.