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

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14
Q

STAGE 3 GLYCOLYSIS

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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
**_MITOCHONDRIA STRUCTURE_**
26
WHAT IS IN THE MATRIX OF THE MITOCHONDRIA?
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.
27
WHAT IS IN THE INNER MEMBRANE OF THE MITOCHONDRIA?
Contains proteins that carry out the oxidation reactions of the electron-transport chain and the ATP-synthase that makes ATP in the matrix.
28
**_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.
29
WHAT ARE THE THREE SUBUNITS OF A PYRUVATE DEHYDROGENASE COMPLEX?
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
**_PYRUVATE DEHYDROGENASE CO-FACTORS_**
31
**_THE PYRUVATE DEHYDROGENASE COMPLEX REACTION_**
32
**_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
33
**_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.
34
WHAT ARE THE FOUR PHASES OF THE TRICARBOXYLIC ACID CYCLE?
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).
35
**_TRICARBOXYLIC ACID CYCLE: STEP 1_**
36
**_THE TRICARBOXYLIC ACID CYCLE: STAGE 2_**
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**_THE TRICARBOXYLIC ACID CYCLE: STAGE 3_**
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**_THE TRICARBOXYLIC ACID CYCLE: STEP 4_**
39
**_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 \_.
Gluconeogenesis Acetyl CoA
40
WHAT EFFECT DOES A HIGH CONCENTRATION OF ACETYL-CoA HAVE ON THE ACTIVITY OF PYRUVATE DEHYDROGENASE COMPLEX?
Decreases the activity
41
WHAT EFFECT DOES HIGH LEVELS OF ACETYL-CoA HAVE ON THE ACTIVITY OF PYRUVATE CARBOXYLASE, AND WHY/HOW?
Increases activity by lowering Km for pyruvate substrate
42
**_THE TRICARBOXYLIC ACID CYCLE_**
43
**_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.
Mitochondria ATP
44
WHERE DOES OXIDATIVE PHOSPHORYLATION TAKE PLACE?
In the mitochondria
45
WHAT ARE THE TWO PARTS OF OXIDATIVE PHOSPHORYLATION?
1. Generation of a proton gradient 2. Production of ATP
46
**_MOVEMENT OF ELECTRONS_**
47
**_CELL MEMBRANE_**
48
**_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.
Proton Synthase ADP
49
WHAT TWO STAGES DOES ATP SYNTHESIS CONSIST OF?
1. Proton transport to mitochondrial inter-membrane space 2. Transport of protons through inner membrane by ATP synthase.
50
**_GLYCOGEN METABOLISM_**
51
**_ATP YIELD FROM DEGRADATION OF GLUCOSE_**
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**_SYNTHESIS OF GLYCOGEN 1,4 BONDS_**
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**_SYNTHESIS OF GLYCOGEN 1,6 BONDS_**
54
**_DEGRADATION OF GLYCOGEN 1,4 BONDS_**
55
WHAT ENZYME DEGRADES GLYCOGEN 1,4 BONDS?
Glycogen Phosphorylase
56
HOW CAN YOU INCREASE THE ACTIVITY OF GLYCOGEN PHOSPHORYLASE?
Glucagon increases the activity of glycogen phosphorylase
57
**_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-\_.
Glucose 6 Transferase Phosphate
58
**_REGULATION OF GLYCOGEN METABOLISM_**
59
WHAT ARE TRIACYL-GLYCERIDES HYDROLYSED TO WHEN DEGRADED?
Fatty acids and glycerol (by lipase)
60
**_DEGRADATION OF TRIACYL-GLYCERIDES_**
61
**_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.
Cytosol
62
IN WHICH TWO ORGANELLES DOES FATTY ACID ß-OXIDATION OCCUR?
Mitochondria Peroxisomes
63
**_ATP FROM ß-OXIDATION_**
64
**_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).
Mitochondria
65
**_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.
CoA
66
**_DIFFERENCES BETWEEN FATTY ACID DEGRADATION AND BIOSYNTHESIS_**
67
**_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).
High Mitochondria Glucagon Phosphate
68
LOW LEVELS OF MALONYL-CoA ALLOW FATTY ACID BIOSYNTHESIS. TRUE OR FALSE?
FALSE High levels allow fatty acid biosynthesis
69
**_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).
Glucose Propanone
70
WHEN WOULD KETOGENESIS OCCUR?
When insufficient glucose is available (can be as a result of starvation or diabetes).
71
UNDER STARVATION CIRCUMSTANCES, WHAT WOULD HAPPEN DURING KETOGENESIS?