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Pharmacy; The Healthy Body 2 > Cellular Respiration&Metabolism > Flashcards

Cellular Respiration&Metabolism Flashcards

1
Q

WHAT IS METABOLISM?

A

The interconversion of biomolecules using chemical reactions

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2
Q

CATABOLIC (DEGRADATIVE) REACTIONS

Production of chemical energy (ATP) and ion gradients

Production of mechanical energy (muscle contraction)

Production of reducing equivalents

Production of biosynthetic precursors

A
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3
Q

ANABOLIC (BIOSYNTHETIC) REACTIONS

Storage of energy

Production of metabolites and cellular structures.

A
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4
Q

GIBBS FREE ENERGY

A
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5
Q

AN ENDOTHERMIC REACTION REQUIRES ENERGY.

TRUE OR FALSE?

A

TRUE

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6
Q

Reactions are often driven by ATP or pyrophosphate hydrolysis (removal of products);

ATP to ADP + Pi = 30.5 KJ mol-1

ATP to AMP + PPi = 45.6 KJ mol-1

A
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7
Q

ATP

A
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8
Q

TRANSPORT OF GLUCOSE INTO CELLS

  • Homeostatic blood glucose level is ~4-8 mM
  • Transport into cells is mediated by a number of glucose transporters (GLUTs)
  • GLUT1 & 3 – Km for glucose ~1 mM. Mediates basal glucose uptake and found in all cell types
  • GLUT 2 – Km for glucose 15 to 20 mM. Only active after carbohydrate rich meal;
  • Liver – Takes up glucose for storage as _.
  • Pancreas – Uptake triggers secretion of insulin. Increases concentration of GLUT4 in well-fed state
  • GLUT4 - Km for glucose 5 mM. Found in muscle and adipose (fat tissue)
  • GLUT 5 – Transports dietary fructose from small intestine. Fructose can be converted to glucose
A

Glycogen

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9
Q

GLYCOLYSIS

Glycolysis literally means ‘sugar splitting’

It is a central pathway within the cell

There are 10 steps starting from glucose, divided into three stages:

  1. Activation and rearrangement (3 steps)
  2. Splitting into phosphorylated C3 sugars (2 steps); 3.Conversion of phosphorylated C3 sugars into pyruvate (5 steps)

It takes place in the cytosol

Overall yield is 2 x pyruvate, 2 x ATP and 2 x NADH molecules

A
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10
Q

WHAT IS THE OVERALL YIELD OF GLYCOLYSIS?

A

2 x pyruvate

2 x ATP

2 x NADH

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11
Q

WHAT ARE THE THREE STAGES OF GLYCOLYSIS?

A
  1. Activation and rearrangement (3 steps)
  2. Splitting into phosphorylated C3 sugars (2 steps)
  3. Conversion of phosphorylated C3 sugars into pyruvate (5 steps)
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12
Q

STAGE 1 GLYCOLYSIS

A
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13
Q

STAGE 2 GLYCOLYSIS

A
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14
Q

STAGE 3 GLYCOLYSIS

A
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15
Q

ANAEROBIC RESPIRATION

A
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16
Q

WHAT DOES THE CORI CYCLE DO?

A

Regenerates R-lactate to glucose

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17
Q

THE CORI CYCLE

A
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18
Q

HOW MANY MOLECULES OF ATP ARE REQUIRED PER GLUCOSE MOLECULE IN THE CORI CYCLE?

A

6

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19
Q

GLUCONEOGENESIS

A
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20
Q

WHERE DOES GLUCONEOGENESIS PRIMARILY OCCUR?

A

Liver

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21
Q

DURING GLUCONEOGENESIS, WHAT IS OXALOACETATE CONVERTED INTO AFTER IT HAS BEEN EXPORTED INTO THE CYTOSOL?

A

Phosphoenolpyruvate

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22
Q

CONTROL OF GLYCOLYSIS AND GLUCONEOGENENSIS

A
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23
Q

WHERE DOES GLYCOLYSIS AND GLUCONEOGENESIS OCCUR?

A

Cytosol

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24
Q

WHAT TWO THINGS CONTROL GLYCOLYSIS AND GLUCONEOGENESIS?

A

Energy levels in the cell

Hormonal control

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25
Q

MITOCHONDRIA STRUCTURE

A
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26
Q

WHAT IS IN THE MATRIX OF THE MITOCHONDRIA?

A

Contains a highly concentrated mixture of hundreds of enzymes, including those required for the oxidation of pyruvate and fatty acids and for the citric acid cycle.

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27
Q

WHAT IS IN THE INNER MEMBRANE OF THE MITOCHONDRIA?

A

Contains proteins that carry out the oxidation reactions of the electron-transport chain and the ATP-synthase that makes ATP in the matrix.

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28
Q

PYRUVATE DEHYDROGENASE COMPLEX

  • Pyruvate dehydrogenase complex controls entry of pyruvate into the TCA cycle. Has 3 types of subunit;
  • Pyruvate dehydrogenase (E1) – decarboxylates pyruvate (requires TPP)
  • Dihydrolipoyl transferase (E2) – makes CoA (requires lipoamide)
  • Dihydrolipoyl dehydrogenase (E3) – converts reduced lipoamide to disulfide form (requires FAD).

Mammals have 30 x E1, 12 x E2 and 12 x E3.

A
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29
Q

WHAT ARE THE THREE SUBUNITS OF A PYRUVATE DEHYDROGENASE COMPLEX?

A

Pyruvate dehyrogenase (E1)- decarboxylates pyruvate (requires TPP)

Dihydrolipoyl transferase (E2)- makes CoA (requires lipoamide)

Dihydrolipoyl dehydrogenase (E3)- converts reduced lipoamide to disulfide form (requires FAD)

30
Q

PYRUVATE DEHYDROGENASE CO-FACTORS

A
31
Q

THE PYRUVATE DEHYDROGENASE COMPLEX REACTION

A
32
Q

THE PYRUVATE DEHYDROGENASE COMPLEX REACTION STEPS

  1. TPP anion adds to pyruvate and CO2 is released
  2. Lipoamide disulfide is added to acetyl group and a redox reaction occurs
  3. Disulfide exchange occurs to form acetyl-CoA and reduced lipoamide
  4. Reduced lipoamide is oxidised to disulfide form using FAD
  5. FADH2 is oxidised by NADH, which is fed into the electron transport system
A
33
Q

THE TRICARBOXYLIC ACID CYCLE

  • The cycle is amphibolic (used in both catabolic and anabolic reactions)

It consists of 8 steps:

  • Four phases
    1. Condensation and rearrangement (steps 1 & 2)
    2. Decarboxylation (steps 3 & 4)
    3. Formation of GTP using phosphate anhydride bond (step 5)
    4. Conversion of succinate to oxaloacetate (steps 6-8) (cf. similarities with fatty acid oxidation – see later).

Acetyl-CoA is oxidised to 2 x CO2 . Other products are: 3 x NADH and H+, 1 x FADH2, 1 x GTP. O2 must be present to allow re-oxidation of reduced cofactors by electron transport system.

A
34
Q

WHAT ARE THE FOUR PHASES OF THE TRICARBOXYLIC ACID CYCLE?

A
  1. Condensation and rearrangement (steps 1 & 2); 2.Decarboxylation (steps 3 & 4)
  2. Formation of GTP using phosphate anhydride bond (step 5); 4.Conversion of succinate to oxaloacetate (steps 6-8) (cf. similarities with fatty acid oxidation – see later).
35
Q

TRICARBOXYLIC ACID CYCLE: STEP 1

A
36
Q

THE TRICARBOXYLIC ACID CYCLE: STAGE 2

A
37
Q

THE TRICARBOXYLIC ACID CYCLE: STAGE 3

A
38
Q

THE TRICARBOXYLIC ACID CYCLE: STEP 4

A
39
Q

ANAPLEROTIC REACTIONS

  • Anaplerotic literally means ‘filling up’
  • TCA cycle is used to provide starting materials for biosynthesis; This results in depletion of oxaloacetate and then _-_ accumulates;
  • High levels of acetyl-CoA decrease activity of pyruvate dehydrogenase complex.
  • High levels of acetyl-CoA increase activity of pyruvate carboxylase by decreasing Km for pyruvate substrate (allosteric curve shifts to left); Net effect is to rebalance oxaloacetate and acetyl-CoA levels.
  • Production of oxaloacetate is also important for _.
A

Gluconeogenesis

Acetyl CoA

40
Q

WHAT EFFECT DOES A HIGH CONCENTRATION OF ACETYL-CoA HAVE ON THE ACTIVITY OF PYRUVATE DEHYDROGENASE COMPLEX?

A

Decreases the activity

41
Q

WHAT EFFECT DOES HIGH LEVELS OF ACETYL-CoA HAVE ON THE ACTIVITY OF PYRUVATE CARBOXYLASE, AND WHY/HOW?

A

Increases activity by lowering Km for pyruvate substrate

42
Q

THE TRICARBOXYLIC ACID CYCLE

A
43
Q

OXIDATIVE PHOSPHORYLATION

Takes place in _.

Requires the presence of O2

Electrons transferred from NADH and FADH2 (produced by glucose and fatty acid oxidation) to O2 via a series of electron donors

Many proteins are inserted into the mitochondrial membrane

Consists of two parts:

  1. Generation of a proton gradient
  2. Production of _

Generates most ATP e.g. 26 of 30 molecules from the complete oxidation of glucose.

A

Mitochondria

ATP

44
Q

WHERE DOES OXIDATIVE PHOSPHORYLATION TAKE PLACE?

A

In the mitochondria

45
Q

WHAT ARE THE TWO PARTS OF OXIDATIVE PHOSPHORYLATION?

A
  1. Generation of a proton gradient
  2. Production of ATP
46
Q

MOVEMENT OF ELECTRONS

A
47
Q

CELL MEMBRANE

A
48
Q

CHEMI-OSMOTIC HYPOTHESIS

ATP synthesis is coupled to the _ gradient (‘Mitchell hypothesis’, 1961)

ATP synthesis consists of:

•1) Proton transport to mitochondrial inter-membrane space; •2) Transport of protons through inner membrane by ATP _.

ATP synthesis from ADP and inorganic phosphate is spontaneous.

A proton gradient is required to drive release of ATP from the enzyme to allow binding of _ and inorganic phosphate.

A

Proton

Synthase

ADP

49
Q

WHAT TWO STAGES DOES ATP SYNTHESIS CONSIST OF?

A
  1. Proton transport to mitochondrial inter-membrane space
  2. Transport of protons through inner membrane by ATP synthase.
50
Q

GLYCOGEN METABOLISM

A
51
Q

ATP YIELD FROM DEGRADATION OF GLUCOSE

A
52
Q

SYNTHESIS OF GLYCOGEN 1,4 BONDS

A
53
Q

SYNTHESIS OF GLYCOGEN 1,6 BONDS

A
54
Q

DEGRADATION OF GLYCOGEN 1,4 BONDS

A
55
Q

WHAT ENZYME DEGRADES GLYCOGEN 1,4 BONDS?

A

Glycogen Phosphorylase

56
Q

HOW CAN YOU INCREASE THE ACTIVITY OF GLYCOGEN PHOSPHORYLASE?

A

Glucagon increases the activity of glycogen phosphorylase

57
Q

DEGRADATION OF BRANCHED GLYCOGEN

Branching of glycogen is required for fast degradation when _ is required.

Glycogen phosphorylase cannot break 1,_-glycosidic bonds; Residues are removed by glycogen phosphorylase until three 1,4 residues are left next to the 1,6-glycosidic bond.

A glycosyl _ moves these three residues onto another chain.

The 1,6-linked residue is removed by a 1,6-glycosidase enzyme which is an retaining enzyme.

The glucose product is either exported or converted to glucose-6-_.

A

Glucose

6

Transferase

Phosphate

58
Q

REGULATION OF GLYCOGEN METABOLISM

A
59
Q

WHAT ARE TRIACYL-GLYCERIDES HYDROLYSED TO WHEN DEGRADED?

A

Fatty acids and glycerol (by lipase)

60
Q

DEGRADATION OF TRIACYL-GLYCERIDES

A
61
Q

FATTY ACID ß-OXIDATION

Fatty acid β-oxidation occurs in two organelles:

  1. Mitochondria – straight-chain fatty acids are degrade to acetylCoA to make ATP
  2. Peroxisomes – Unusual fatty acids are degraded to get rid of them. No ATP is made (in mammals).

The acyl-CoA is (usually) made in the _.

Acyl-CoA are imported into the mitochondria using the acylcarnitine shuttle.

β-Oxidation in both organelles have the same intermediates and reactions. The enzymes performing the steps are different (details not important!).

The n-2 fatty acyl-CoA can be further β-oxidised.

A

Cytosol

62
Q

IN WHICH TWO ORGANELLES DOES FATTY ACID ß-OXIDATION OCCUR?

A

Mitochondria

Peroxisomes

63
Q

ATP FROM ß-OXIDATION

A
64
Q

FATTY ACID BIOSYNTHESIS

Fatty acid biosynthesis requires acetyl-CoA and CO2.

Acetyl-CoA is made in the _ by pyruvate dehydrogenase complex.

Carboxybiotin and acetyl-CoA are used to make malonyl-CoA. Acetyl-CoA carboxylase is the key regulatory enzyme and is located in the endoplasmic reticulum.

ATP and CO2 are required to make carboxy-phosphate and carboxybiotin.

The other biosynthetic enzymes are location in the cytosol – transport of acetyl-CoA is required from mitochondria. Biosynthesis requires input of reducing power (NADPH and H+ from pentose phosphate pathway).

A

Mitochondria

65
Q

ACYL CARRIER PROTEIN (ACP)

ACP has the same side-chain as _.

Side-chain is covalently linked to enzyme.

Intermediates are moved from one active site to the next.

The biosynthetic pathway has 4 steps:

  1. Condensation (bond formation)
  2. NADPH-dependent reduction of ketone
  3. Dehydration
  4. NADPH-dependent reduction of double bond.

Each cycle adds a saturated C2 unit.

A

CoA

66
Q

DIFFERENCES BETWEEN FATTY ACID DEGRADATION AND BIOSYNTHESIS

A
67
Q

REGULATION OF FATTY ACID BIOSYNTHESIS AND DEGRADATION

The key process is synthesis of malonylCoA.

_ levels of malonyl-CoA allow fatty acid biosynthesis.

Malonyl-CoA inhibits import of fatty acids into _ for degradation.

_ phosphorylates acetyl-CoA carboxylase and reduces activity (promotes fatty acid degradation).

Insulin promotes removal of _ from acetyl-CoA carboxylase and activates the enzyme (promotes fatty acid synthesis).

A

High

Mitochondria

Glucagon

Phosphate

68
Q

LOW LEVELS OF MALONYL-CoA ALLOW FATTY ACID BIOSYNTHESIS.

TRUE OR FALSE?

A

FALSE

High levels allow fatty acid biosynthesis

69
Q

KETOGENESIS

  • Ketogenesis occurs when insufficient _ is available. This can be due to starvation or diabetes (when available glucose cannot be utilised).
  • Under starvation circumstances glucagon signalling promotes gluconeogenesis and fatty acid β-oxidation
  • Fatty acid produces acetyl-CoA. This can be converted into the ketone bodies acetoacetate and 3-hydroxybutyrate.
  • Ketone bodies are ‘water-soluble’ versions of fats that can be moved around the body and used as fuels.
  • Ketone bodies can be converted into _ (a.k.a. acetone) – produces ketosis (symptom of diabetes).
A

Glucose

Propanone

70
Q

WHEN WOULD KETOGENESIS OCCUR?

A

When insufficient glucose is available (can be as a result of starvation or diabetes).

71
Q

UNDER STARVATION CIRCUMSTANCES, WHAT WOULD HAPPEN DURING KETOGENESIS?

A

Pharmacy; The Healthy Body 2 (10 decks)

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