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Biochemistry > Intermediary metabolism > Flashcards

Intermediary metabolism Flashcards

1
Q

What do aspirin, viagra and penicillin have in common?

A

They are enzyme inhibitors

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2
Q

What does an enzyme affect during a reaction?

A

The transition state

Less activation energy needed to reach transition state

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3
Q

Which 2 parameters characterize enzymes?

A
  • Vmax
  • Km
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4
Q

Does hexokinase or glucokinase have a higher Vmax?

A

Glucokinase

So, hexokinase is saturated faster

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5
Q

Does hexokinase of glucokinase have a higher Km?

A

Glucokinase

Glucokinase acts as a sensor

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6
Q

In which type of cells is hexokinase found in?

A

All other body cells

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7
Q

Which type of cells is glucokinase found in?

A
  • Hepatocytes
  • Pancreatic B cells
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8
Q

How is competitive inhibition reversible?

A

Increase the substrate

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9
Q

What enzyme parameter is changed by competitive inhibitors?

A

Km

More time needed to reach Vmax

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10
Q

Which enzyme parameter is changed by non-competitive inhibitors?

A

Vmax

Lower

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11
Q

What is allosteric regulation?

A

Shifting the equilibrium between active and inactive enzyme conformations.

Inhibitor shifts equilibirum to the right. Activator shifts equilibrium

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12
Q

How is glycogen phosphorylase allosterically acivated?

A
  • AMP binds outside of the active site
  • Phosphorylase kinase attaches phosphates outside of the active site

Phosphorylation can either activate or deactivate an enzyme, mostly acti

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13
Q

How are enzymes regulated?

A
  • Competitive inhibition
  • Allosteric regulation
  • Hormonal regulation (via phosphorylation)
  • Gene transcription
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14
Q

What regulation of enzymes does glucagon activate?

A

Phosphorylation by activating protein kinase A by cAMP second messenger

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15
Q

How does insulin regulate phosphorylation?

A

Insulin inhibits the activation of protein kinase A

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16
Q

How does active protein kinase A increase gluconeogenesis?

A
  1. Protein kinase A activates phosphorylase kinase
  2. Phosphorylase kinase activates glycogen phosphorylase
  3. Protein kinase A phosphorylates glycogen synthase (deactivation)

These enzymes are activated by phosphorylation

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17
Q

Do muscles respond to glucagon or epinephrine?

A

Epinephrine

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18
Q

How does epinephrine regulate glycogen phosphorylase?

A
  1. Epinephrine stimulates Ca+ release from the ER
  2. Ca+ stimulates protein kinase C
  3. Ca+-calmodulin activates calmodulin dependent protein kinase and phosphorylase kinase
  4. Protein kinase C, calmodulin dependent kinase and phosphorylase kinase inactivate glycogen synthase
  5. Phosphorylase kinaseactivates glycogen phosphorylase
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19
Q

What happens when there is a prolonged need for an enzyme?

A

Increased gene transcription

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20
Q

At which two levels is human metabolism controlled?

A
  • Intracellular metabolites
  • Hormones and neuronal signals
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21
Q

To which three substances can glucose-6-phosphate convert to?

A
  • Glycogen via glucose-1-phosphate
  • Pyruvate via fructose-6-phosphate
  • Ribose-5-phosphate via 6-phosphate gluconate
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22
Q

To which substances can pyruvate be converted to?

A
  • Alanine
  • Lactate
  • Oxaloacetate
  • Glucose-6-phosphate via oxaloacetate
  • Acetyl CoA

Conversion t Acetyl CoA is decisive step!!

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23
Q

To which substances can Acetyl CoA be converted to?

A
  • Fatty acids
  • CO2
  • Cholesterol via 3-hydroxy-3-methyl-glutaryl CoA
  • Ketone bodies via 3-hydroxy-3-methyl-glutaryl CoA
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24
Q

What are the three main fates of glucose?

A
  • Glycogen via glucose-1-phosphate
  • Pentose phosphate pathway via ribose-5-phosphate
  • Pyruvate via Fructose-6-phosphate
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25
Q

UDP-glucose from glucose-1-phosphate has which fates?

A
  • Glycogen
  • Lactose via UDP-galactose
  • Glucuronides via UDP-glucuronate
  • Glycoproteins, glycolipids and proteoglycans via UDP galactose and UDP glucuronate

glucuronides make susbstances water soluble

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26
Q

Function of NADPH produced from the PPP?

A
  • Biosynthesis
  • Prevention of oxidative damage
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27
Q

How is glycolysis inhibited?

A
  • Glucose-6-phosphate inhibits hexokinase
  • ATP
  • Citrate inhibits phosphofructokinase
  • Acetyl CoA inhibits pyruvate dehydrogenase

citrate is first metabolite in citric acid cycle

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28
Q

How is glycolysis supported?

A
  • AMP
  • Fructose-2,6-biphosphate activates phosphofructokinase
  • Fructose-1,6-biphosphate activates pyruvate kinase
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29
Q

When glycogenolysis starts, how long during fasting does this occur?

Glycogenolysis is breakdown of glycogen to produce glucose and energy

A

About 24 h

Until glycogen storage is depleted

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30
Q

Role of fructose-2,6-phosphate on glycolysis pathway?

A

It activates phosphatefructokinase 1, activating glycolysis and inhbiting gluconeogenesis

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31
Q

Which hormone controls the speed of gluconeogenesis?

A

Glucagon

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32
Q

Which enzyme does glucagon regulate to initiate gluconeogenesis?

A

Pyruvate kinase is activated (dephosphorylation)

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33
Q

Pyruvate is not converted to acetyl CoA but to what substance during gluconeogenesis?

A

Oxaloacetate under activation of pyruvate carboxylase by acetyl CoA itself

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34
Q

How is glucose made from pyruvate during gluconeogenesis?

A
  1. From pyruvate to oxaloacetate via glucose carboxylase
  2. From oxaloacetate to phosphoenolpyruvate
  3. To glyceraldehyde-3-phosphate
  4. To fructose-1,6-biphosphate
  5. To Fructose-6-phosphate by Fructose-1,6-biphosphatase
  6. To glucose-6-phosphate
  7. To glucose by glucose-6-phosphatase

Gluconeogenesis only in the liver

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35
Q

How much of all glucose enters the PPP?

A

30%

36
Q

Which compound is produced that also stimulates fatty acid synthesis for example?

A

2 NADPH from 2 NADP+

Only produced via oxidative pathway

37
Q

Via which metabolite is ribose-5-phosphate produced if the pathway is oxidative?

A

Glucose-6-phosphate

38
Q

Via which metabolite is ribose-5-phosphate porduced if the pathways is non-oxidative?

A

Fructose-6-phosphate

39
Q

What is a nucleoside

A

A 5 carbon molecule, usually a ribose molecule with a nitrigenous base

40
Q

From which substance are nucleotides made of?

A

Ribose-5-phosphate

41
Q

What is the difference between nucleosides and nucelotides?

A

Nucleotides are nucleosides with 1,2 or 3 phosphate groups attached

42
Q

Which nucleosides make up nucleotides in DNA?

A
  • Adenine
  • Guanine
  • Cytosine
  • Thymine
43
Q

Which nucleosides are purines?

A
  • Adenine
  • Guanine
44
Q

Which nucleosines are pyrimidines?

A
  • Thymine
  • Cytosine
45
Q

Which enzyme facilitates the conversion of ribose-5-phosphate to 5-phosphoribosyl 1-pyrophosphate (PRPP)

A

PRPP synthetase

46
Q

Which activated molecule supports nucleotide production?

A

5-phosphorybosyl 1-pyrophosphate (PRPP)

47
Q

Which molecules are needed to go from an amino acid to uridine monophosphate (UMP) during pyrimidine synthesis?

A
  • Carbamoyl phosphate
  • PRPP
  • Ribose-5-phosphate
48
Q

How is carbomoyl phosphate produced in pyrimidine synthesis?

A

Glutamine+CO2+2ATP

49
Q

What is uridinyl monophosphate (UMP)?

A

An intermediate in pyrimidine synthesis

50
Q

What is the difference between purine and pyrimidine synthesis?

A
  • PRPP is still formed, however:
  • PRPP and glutamine together form IMP as an intermediate
  • A lot of ATP (6) is used for 11 steps
51
Q

Which enzyme facilitates the formation of dNDP’s from NDP?

A

Ribonucleotide reductase

It removes an alcohol group and adds an H+ instead

52
Q

Which molecule that is produced during the oxidative PPP is used during production of dNDP’s?

A

NADPH

So, if there is alot of NADPH, nucleotide synthesis is activated

53
Q

For which disease was 5-Fluorouracil (5-FU) used?

A

Cancer, to block DNA synthesis

54
Q

How does 5-FU inhibit DNA synthesis?

A

5-FU is an analogue of uracil or thymine, but with a fluor group added where binding between nucleotides is supposed to occur. As a result no basepairing and DNA synthesis stops.

55
Q

Which amino acids are needed during pyrimidine synthesis?

A
  • Glutamine to produce carbamoyl phosphate
  • Aspartate
56
Q

What does pyruvate dehydrogenase do?

A

Metabolizes pyruvate into acetyl CoA

PDH is therefore an important factor to regulate to determine glucose fa

57
Q

Can acetyl CoA be used to synthesise glucose?

A

No

58
Q

When is fat produced?

A

When insulin is produced and glycogen storage is full

59
Q

Which enzyme activated PDC?

A

Phosphatase stimulated by insulin

Ca+ also activates the enzyme

60
Q

Which enzyme deactivates PDC?

A

Kinase which adds a phosphate

61
Q

Which other factors regulate the deactivation of PDC by kinase?

A
  • ADP inhibits inactivation (If alot is formed during PDC inactivation)
  • Pyruvate inhibits inactivation (If there is alot of pyruvate)
  • Acetyl CoA activates kinase (To stop xtra CoA forming)
  • NADH activates kinase (To stop xtra NADH forming)
62
Q

Which substances regulate TCA cycle?

A
  • Citrate inhibits citrate synthase
  • NADH inhibits more formation of NADH
  • ADP activates TCA cycle as ADP can be used to generate ATP in the electron transport system
  • Ca+ activates cycle by insulin
63
Q

When is fatty acid synthesis a fully comitted step?

A

If malonyl-CoA is produced from acetyl-CoA by acetyl-CoA carboxylase

64
Q

How is acetyl-CoA carboxylase regulated?

A
  • At hormonal level by insulin and glucagon
  • At cellular level by citrate and AMP
65
Q

When is acetyl carboxylase activated?

A
  • When citrate binds to inactive carboxylase
  • When insulin activates protein phosphatase to remove the phosphate group
66
Q

When is acetyl CoA inactivated?

A
  • When glucagon activates protein kinase to bind a phosphate group
  • When there is a surplus of AMP, protein kinase is inactivated
67
Q

How do beta-oxidation and fatty acid synthesis never occur simultaneously?

A

Malonyl-CoA inhibtis FA CoA from entering the mitochondria

68
Q

By which two metabolites is fatty acid metabolism regulated?

A
  • Citrate activates acetyl CoA carboxylase
  • Palmitoyl CoA inhibits acetyl CoA carboxylase
69
Q

What funtion does glucose have for adipose cells?

A

Glycerol is made from glucose to make triglycerides

70
Q

Which enzyme is stimulated by insulin in order to facilitate fatty acids entering adipose cells?

A

Lipoprotein lipase

71
Q

Which GLUT transporter is insulin dependent?

A

GLUT4

72
Q

Glucagon does what to PDC?

A

It deactivates it in order to convert pyruvate onto oxaloacetate

73
Q

From which metabolite does gluconeogenesis start?

A

Oxaloacetate

74
Q

Which are mobilized first: fatty acids or amino acids?

A

Amino acids

This is seen by the increase of nitrogenous products in urine

75
Q

What effect does glucagon have on adipose cells?

A
  • Glucagon activates cAMP
  • cAMP activates protein kinase A
  • Protein kinase A activates adipocyte triglyceride lipase
  • Fatty acids and glycerol transported into the blood
76
Q

Four fates of acetyl CoA are?

A
  • TCA cycle
  • Fatty acid synthesis
  • Ketone bodies
77
Q

During fasting, which compound is used for glucose production?

A

Glycerol from adipose tissue

78
Q

During fasting, fatty acids are used to produce what to generate energy in the muscle?

A

Acetyl CoA

79
Q

During fasting fatty acids transported to the liver are used to make what compound that can be used by the brain and muscles?

A

Ketone bodies

80
Q

During fasting, ketone bodies are converted into what in the muscle to generate energy?

A

Acetyl CoA

81
Q

Describe ketone body production in short

A
  1. Two acetyl CoA molecules produce acetoacetate
  2. Acetoacetate can be spontaneously converted to acetone, releasing CO2
  3. Acetoacetate can be converted to beta-hydroxybutyrate bybeta-hydorxybutyrate dehydrogenase
82
Q

Describe ketone body to acetyl CoA in short

A
  1. Beta-hydroxybutyrate into acetoacetate
  2. Acetoacetate into acetoacetyl CoA
  3. Acetoacetyl CoA into two molecules of acetyl CoA
83
Q

During starvation which tissue uses glucose alot

A

nervous system

84
Q

During starvation, which tissues use fatty acid as fuel?

A
  • Skeletal muscle
  • Heart muscle
  • Liver
  • Kidney a bit
85
Q

Which tissues use ketone bodies during starvation?

A
  • Nervous system
  • Skeletal muscle
  • Heart muscle
  • Intestinal epithelial cells
  • Kidney a bit

Liver does NOT use ketone bodies

86
Q

How does epinephrine influence glucose mobilization?

A

Glucose is produced from triglycerides, pyruvate and lactate (muscle) and glycogen to increase blood glucose levels

Biochemistry (13 decks)

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