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Exam 1 Information > Oxidative Metabolism > Flashcards

Oxidative Metabolism Flashcards

1
Q

Oxidative metabolism

A

Oxidation of carbohydrates, lipids or proteins

Primary purpose is production of energy, which is stored as adenosine triphosphate (ATP)

ATP molecules contain high-energy phosphate bonds, which are the basis for energy storage

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2
Q

Example of energy-rich compounds

A
  • Acid anhydrides
  • Enol phosphates
  • Thioesters
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3
Q

Glycolysis

A

Process in which glucose (a 6c sugar) is oxidized to pyruvic acid (pyruvate, a 3C keto-acid)

CH3-CO-COO-

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4
Q

Irreversible enzymes in Glycolysis

A

Hexokinase

PFK

Pyruvate kinase

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5
Q

Red blood cells and lactic acid

A

In the blood cell, glucose goes to pyruvate which is the reduced to lactate– moves blood cell into the bloodstream

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6
Q

Products of Glycolysis

A

2 NADH

2 ATP

2 Pyruvates

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7
Q

When is ATP used in Glycolysis

A

During the irreversible reactions

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8
Q

Hexokinase

A
  • Inhibited by glucose-6-phosphate in most tissue
  • The isozyme glucokinase, or Hexokinase-4, expressed in the liver and in the beta-cells of pancreas, has high Km for glucose, and is not inhibited by glucose 6-P
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9
Q

PFK-1

A

Phosphofructokinase (PFK-1)

Removes phosphate from ATP and adds to fructose 6-phosphate to form fructose 1,6 bisphosphate

  • committed (rate-limiting) step of glycolysis
  • inhibited by ATP, citrate
  • activated by AMP
  • activated by fructose-2,6-bisphosphate
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10
Q

PFK-2 vs.FBPase2

A

When hydrolyzed, PFK2 is active and FBPase2 is inactive

When phosphorylated, PFK-2 is inactive and FBPase2 is active

Uses cAMP-dependent PKA to phosphorylate, making FBPase2 active

Uses Phosphoprotein Phosphatase (PP1) to make PFK-2 active

When PFK-2 is active–

  • increase production of Fructose 2,6-BP
  • increases in PFK-1 activity
  • increase glycolysis

Less active for PFK-2 and more active for F 2,6-bisphosphate, thus decreasing fructose 2,6 bisphosphate, and inhibiting glcolysis

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11
Q

Pyruvate kinase

A
  • inhibited by ATP and alanine
  • activated by PFK-1 product
  • inhibited by phosphorylatoin
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12
Q

Phosphorylation of pyruvate kinase in response to high ATP in cytosol

A

Low blood Glucose level – Pyruvate is phosphorylated using ATP. Pyruvate kinase is less active

High Blood Glucose level
-Pyruvate kinase is dephosphorylated and pyruvate kinase is more active

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13
Q

How does insulin stimulate glycolysis

A

Increasing fructose-2,6-P2
-causes a phosphodiesterase to hydrolyze cyclic AMP:
cyclic AMP -> AMP+Pi
-Insulin also causes protein phosphatases to dephosphorylate regulatory enzymes
-PFK-2 enzyme in liver is stimulated, leading to increased concentration of fructose 2,6-bisphosphate

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14
Q

GLUT-1

GLUT-2

GLUT-3

GLUT-4

GLUT-5

A

GLUT-1 -> all tissues

GLUT-2 -> liver, pancrea (beta cells)
GLUT-3 -> all tissues

GLUT-4 -> cardiac and skeletal muscle, adipose tissue
GLUT-5: Small intestine, liver, muscle, other tissues
*insulin causes movement of GLUT_4 receptors from cytosol to plasma membrane

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15
Q

FBPase2 active

A

Converts F2,6-BP to fructose-6-P

  • Increase in gluconeogenesis
  • Decrease in glycolysis
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16
Q

Epinephrine works like…

A

Glucagon. Inhibits glycolysis

17
Q

Pyruvate kinase deficiency

A
  • Rarely seen genetic defect of glycolysis (1/20,000 of Northern European descent)
  • Effects the erythrocyte-specific isozyme of pyruvate kinase
  • May severely limit Erythrocyte ATP synthesis
  • Causes hemolytic anemia (RBC lysis)
18
Q

Hypoxia-induced factor (HIF-1)

A

Factor causes increased transcription of mRNA for glycolytic enzymes and the basal glucose transporters GLUT-1 and GLUT-3

19
Q

Oxidation of pyruvate location

A

Oxidized within the mitochondria to form Acetyl Coenzyme A

20
Q

2 routes of Acetyl CoA

A
  • metabolized in mitochondria to make ATP

- transferred to cytosol for biosynthesis of fatty acids and sterols

21
Q

Nucleotide derivatives

A

Serve as “activated” metabolite carriers

22
Q 
Nucleotide derivative carriers:
Coenzyme A
UDP
CDP
FAD, NAD, NADP
A

Coenzyme A: carrier of acyl group

UDP: carbohydrate carrier UDP-glucose)

CDP: lipid carrier (CDP-diacylglycerol)

FAD, NAD, NADP: electron carriers

23
Q

PDH Complex

A

Pyruvate Dehydrogenase complex

  • decarboxylation of pyruvate
  • Pyruvate is oxidized, CO2 released
24
Q

TCA cycle

A

-oxidation of 2-carbon Acetyl-CoA units, releasing 2CO2
-production of reducing equivalents (NADH, FADH2)
-generation of energy in the form of
ATP– oxidative phosp
GTP– substrate phosp

25
Q

alpha-keto glutarate dehydrogenase requires:

  • Creates:
  • Inhibited by:
A
  • thiamine pyrophosphate
  • lipoic acid
  • FAD
  • Creates Succinyl Coenzyme A and NADH
  • Inhibited by Arsenite (ASO2)
26
Q

Regulations of PDH complex

A
  1. Allosteric inhibition (or activation) by metabolites:
    Acetyl CoA and NADH inhibit (Coenzyme A and NAD+ stimulate)
  2. Covalent modification of PDH complex:
    Phosphorylation of serine on transacetylase (2) inhibits activity. The phosphorylated form is inactive, while the dephosphorylated form is active.
  3. Hormonal regulation:
    PDH activity is increased by insulin (most tissues), and also by epinephrine (cardiac muscle)
27
Q

TCA cycle is regulated generally by:

A

1) Availability of Acetyl CoA (generated by pyruvate DH, and by fatty acid b-oxidation)
(2) Availability of oxidized NAD+ and FAD.
(NAD+/NADH ratio – redox potential)
(3) ATP to ADP+AMP ratio (influences activity of regulatory kinases)
(4) Activity of the mitochondrial respiratory chain (ETS),

28
Q

TCA cycle is regulated specifically by:

A

1) ATP, citrate and succinyl CoA inhibit citrate synthase
2) ATP, NADH inhibit isocitrate dehydrogenase (ADP, AMP, and NAD+ stimulate)
2) NADH inhibits a-ketoglutarate dehydrogenase
3) ATP, GTP, and succinyl CoA also inhibit
a-ketoglutarate dehydrogenase

4) Malonic acid inhibits succinate dehydrogenase
5) Fluoroacetate inhibits aconitase

29
Q

Cycle intermediates:

A

Citrate - formation of acetyl CoA for synthesis of
fatty acids, sterols
a-ketoglutarate - formation of glutamate, glutamine
Succinyl CoA - porphyrin (heme) synthesis
Oxaloacetate – aspartate, asparagine, nucleotides
carbohydrate synthesis (gluconeogenesis)

30
Q

Malate-Aspartate shuttle

A

NADH to mitochondria

-expressed primarily in liver and cardiac muscle

31
Q

alpha-glycerol phosphate shuttle

A

NADH to mitochondrion

-expressed in most tissues

32
Q

tricarboxylate shuttle

A

Acetyl CoA to cytosol

Exam 1 Information (14 decks)

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