Enzymes Involved in Metabolism Flashcards

1
Q

glucokinase

  1. Used for…
  2. Relationship to metabolism…
A
  1. phosphorylates glucose to glucose-6-phosphate (and is not subject to product inhibition)
  2. LIVER ENZYME ONLY (?)
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2
Q

Hormone Sensitive Lipase (HSL)

  1. Used for…
  2. Relationship to metabolism…
A
  1. degrades triglycerides in adipose tissue

2. Insulin inhibits HSL by promoting its dephosphorylation (inactivation). Thus, insulin decreases TG breakdown.

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3
Q

Glycerol-3-Phosphate

  1. Used for…
  2. Relationship to metabolism…
A
  1. Backbone of for trigylceride synthesis

2. Glucose mobilization into Adipocytes via insulin provides Glycerol-3-Phosphate as a substrate for TG synthesis

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4
Q

Lipoprotein Lipase (LPL)

  1. Used for…
  2. Relationship to metabolism…
A
  1. Allows for drop off (release) of fatty acids from chylomicrons, which are subsequently for TG synthesis and storage in adipocytes
  2. insulin increases synthesis of Lipoprotein Lipase
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5
Q

Insulin sensitive glucose transporters

A

GLUT 4 (in skeletal & cardiac muscle and adipocytes)

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6
Q

Pyruvate Kinase

  1. Used for…
  2. Relationship to metabolism…
A

1.

2.

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7
Q

Acetyl CoA Carboxylase

  1. Used for…
  2. Relationship to metabolism…
A
  1. Catalyzes reaction of Acetyl Coa –> Malonyl CoA (rate-limiting run for FA synthesis!)
  2. in fed state, insulin levels result in an increased synthesis of this enzyme. Malonyl CoA subsequently inhibits fatty acid oxidation.
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8
Q

Fatty Acid Synthase

  1. Used for…
  2. Relationship to metabolism…
A

1.

2.

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9
Q

Adenylyl Cyclase

  1. Used for…
  2. Relationship to metabolism…
A
  1. Causes signaling cascade leading to phosphorylation
  2. Activated by glucagon binding at the plasma membrane –> activates cAMP-dependent protein Kinase –> phosphorylation of enzymes (resulting in activation or inactivation)
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10
Q

Alcohol dehydrogenase

  1. Used for…
  2. Relationship to metabolism…
A
  1. Converts ethanol to acetaldehyde by reducing NAD+ to NADH
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11
Q

Aldehyde Dehydrogenase

  1. Used for…
  2. Relationship to metabolism…
A
  1. converts Acetaldehyde to Acetate by reducing NAD+ to NADH
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12
Q

fructose-2,6-bisphosphate

  1. Used for…
  2. Relationship to metabolism…
A
  1. Allosteric activator of phosphofructokinase-1 (PFK1) and allosteric inhibitor of fructose-1,6-bisphosphatase
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13
Q

Phosphofructokinase-1 (PFK1)

  1. Used for…
  2. Relationship to metabolism…
A
  1. glycolysis
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14
Q

Fructose-1,6-bisphosphatase

  1. Used for…
  2. Relationship to metabolism…
A
  1. gluconeogenesis
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15
Q

Fructose-1,6-bisphosphatase

  1. Used for…
  2. Relationship to metabolism…
A
  1. gluconeogenesis
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16
Q

HMG-CoA Reductase

A
  1. involved in anabolic metabolism

2. in fed state, insulin levels result in an increased synthesis of this enzyme

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17
Q

HMG-CoA Reductase

  1. Used for…
  2. Relationship to metabolism…
A
  1. involved in anabolic metabolism

2. in fed state, insulin levels result in an increased synthesis of this enzyme

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18
Q

Glycogen Synthase

  1. Used for…
  2. Relationship to metabolism…
A
  1. conversion of glucose-6-phosphate to glycogen

2. activated by dephosphorylation AND by increased availability of glucose-6-phosphate (allosteric effector)

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19
Q

NADPH used in what kind of reactions

A

synthesis reactions ?

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20
Q

NADH and NADPH are

A

reducing equivalents?

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21
Q

NAD+ used in what kind of reactions

A

oxidation reactions ?

22
Q

HMP Pathway (Hexose monophosphate)

A

Produces NADPH, which is required for fat synthesis

23
Q

Acetyl CoA

A

used as a building block for fatty acid synthesis
OR
provides energy by oxidation in the TCA cycle

ALSO- allosteric activator of pyruvate carboxylase which pushes towards gluconeogenesis. It is an allosteric inhibitor of pyruvate dehydrogenase (pyruvate–>lactose?)

24
Q

Pyruvate Carboxylase

  1. Used for…
  2. Relationship to metabolism…
A
  1. Catalyzes first step in gluconeogenesis
  2. Inactive when there are low levels of Acetyl CoA –> meaning that the acetyl CoA is being used for fatty acid synthesis
25
Q

Fatty acid synthesis favored by…

A

Availability of substrates: Acetyl CoA and NADPH
&
Activation of Acetyl CoA Carboxylase: by dephosphorylation and presence of allosteric activator Citrate

26
Q

Hexokinase

  1. Used for…
  2. Relationship to metabolism…
A
  1. phosphorylates glucose to glucose-6-phosphate in SKELETAL MUSCLE
  2. increase in glucose-6-phosphate favors glycogen synthesis, especially if glycogen stores have been depleted as a result of exercise
27
Q

Transaminase

  1. Used for…
  2. Relationship to metabolism…
A
  1. degradation of branched-chain amino acids (leucine, isoleucine, valine) in MUSCLE ONLY
  2. branched-chain amino acids escape metabolism by the liver are are subsequently used in muscle for protein synthesis and as a source of energy
28
Q

Glucose-6-phosphatase

  1. Used for…
  2. Relationship to metabolism…
A

1.

2. Allows production of free glucose from both glycogenolysis and gluconeogenesis

29
Q

Where are the carbon skeletons for gluconeogenesis derived?

A

glucogenic amino acids & lactate from muscle.

glycerol from adipose.

30
Q

Ketogenesis is favored when…

A

The concentration of Acetyl CoA (from FA B-oxidation) exceeds the oxidative capacity of the TCA Cycle

31
Q

After 3 weeks of fasting, muscle…

A

muscle decreases its use of ketone bodies from the liver as fuel. It oxidizes fatty acids almost exclusively. This then leads to a further increase in the already elevated levels of ketone bodies.

32
Q

After 3 weeks of fasting, muscle…

A

muscle decreases its use of ketone bodies from the liver as fuel. It oxidizes fatty acids almost exclusively. This then leads to a further increase in the already elevated levels of ketone bodies.

33
Q

Important glucogenic amino acids released from muscle…

A

Alanine and glutamine… which are produced by the catabolism of branched-chain amino acids

34
Q

glutamine is released from muscle’s metabolism of branched-chain amino acids and is taken up by the kidney, and……

A

is converted to a-ketoglutarate (+ ammonia, NH3) by renal glutaminase and glutamate dehydrogenase.

a-ketoglutarate can be used as a substrate for gluconeogenesis.

NH3 picks up H+ from keto body dissociation and is excreted in urine as NH4+ (ammonium). This would cause a shift in increased urine ammonium and decreased urine urea.

35
Q

essential fatty acids

A

omega-6 fatty acids (precursor of arachidonic acid) and omega-3s????

36
Q

lactate dehydrogenase

A

pyruvate –> lactate

when NADH/NAD+ ratio is high, reaction is virtually irreversible, favoring lactose formation and DEPLETING the gluconeogenic substrate, PYRUVATE (alcohol!!!)

37
Q

pyruvate dehydrogenase

A

pyruvate –> acetyl CoA

38
Q

High NADH/NAD+ ratio favors…

A

pyruvate –> lactate
oxaloacetate –> malate (by malate dehydrogenase)

*High NADH/NAD+ suppresses gluconeogenesis

39
Q

Tissues unaffected by insulin levels

A

brain and RBCs and liver (dbl check?)

40
Q

insulin effect on HSL

A

inhibits –> decreases lipolysis

41
Q

insulin effect on LPL

A

stimulates –> which provides fatty acids for synthesis of TGs

42
Q

Skeletal muscle lacks what receptors?

A

glucagon (it mainly acts on the liver)

43
Q

Metabolic effects of glucagon on carbs, fat, & protein

A
  • CARB: Increases blood glucose by stimulating glycogen breakdown and gluconeogenesis, and by inhibiting glycogen synthesis.
  • FAT: Inhibits FA synthesis, and stimulates FA oxidation and ketone bodies production.

-PROTEIN: Stimulates amino acid uptake
and oxidation thus providing the carbon skeleton of amino acids for gluconeogenesis.

44
Q

mechanism of action of glucagon

A

Glucagon exerts its effects by activating PKA. PKA phosphorylates specific enzymes which results in their activation or inhibition (depending on enzyme).

45
Q

Metabolic effects of catecholamines (epic and norepi)

A

-Effects very rapid and antagonistic to insulin.
-Stimulate lipolysis in adipose tissue.
-Stimulate gluconeogenesis and glycogen breakdown in
the liver.
-Stimulate glycolysis, glycogen breakdown and fatty acid oxidation in skeletal muscle.

-The effects of catecholamines are mediated by elevation of cellular cAMP and/or Ca2+ levels.

46
Q

KEY Junctions in metabolism

A

A. Glucose-6-phosphate

B. Pyruvate and acetyl CoA

47
Q

Phosphoenolpyruvate Carboxykinase (PEPCK)

  1. Used for…
  2. Relationship to metabolism…
A

Gluconeogenic enzyme

Inhibited by insulin signaling

48
Q

Protein Kinase A

  1. Used for…
  2. Relationship to metabolism…
A

Activated by an increase in cAMP in cells. In hepatocytes, cAMP levels increase primarily in response to glucagon and epinephrine.

49
Q

AMPK (AMP Kinase)

A

AMPK is activated when AMP levels are high. AMP levels accumulate when there have been many ATP-requiring reactions occurring.

50
Q

Metformin

A

Activates AMPK. AMPK inhibits gluconeogenesis (by inhibiting PEPCK and G6P-ase) and lipogenesis, while promoting fatty acid oxidation and glycolysis.