Energy production- Carbohydrate Flashcards Preview

Z OLD ESA 1- Metabolism > Energy production- Carbohydrate > Flashcards

Flashcards in Energy production- Carbohydrate Deck (471):
1

What common product are glucose, fatty acids and alcohol broken down into?

Acetyl CoA

2

What is glucose converted into prior to Acetyl CoA?

Pyruvate

3

What else can be converted into Acetyl CoA?

Keto-acids

4

Where do keto-acids come from?

The break down of amino acids

5

What is the advantage of amino acids, glucose, fatty acids and alcohol all being capable of conversion into Acetyl CoA?

It allows for interconversion

6

What is acetyl CoA ultimately converted too?

CO 2

7

Other than keto-acids, what can amino acids be converted into?

NH 3

8

What is NH 3 ultimately converted into?

Urea

9

What are the 4 stages of catabolism?

- Breakdown to building block materials 
- Breakdown of metabolic intermediates 
- TCA (Kreb’s cycle) and release of reducing power and energy
- Oxidative phosphorylation and conversion of reducing power into ATP

10

What is the purpose of breaking food down into building block materials?

To convert nutrients to a form that can be taken up by cells

11

Where does breaking down of substances into building blocks occur?

Extracellular, in the GI tract, technically outside of the body

12

How do the building block materials get into the body?

They are absorbed by epithelial cells in the GI tract

13

What happens to building block materials once they have been absorbed by epithelium in the GI tract?

They are bought into circulation for use

14

What is necessary for absorption of building block materials by the GI tract?

Transport mechanisms in the membrane

15

Does breaking down into building block materials release energy?

No

16

What bonds are broken when producing building block materials?

C-N and C-O 
No C-C

17

Is breakdown into metabolic intermediates and release of reducing power intracellular or extracellular?

#NAME?

18

What cells does breakdown into metabolic intermediates and release of reducing power occur in?

Cells at target organs

19

Is breakdown into metabolic intermediates and release of reducing power a cytosolic or mitochondrial process?

Can be both

20

What is the result of some reactions in the breakdown into metabolic intermediates and release of reducing power being packaged away?

Gives control over synthesis and catabolism

21

Is breakdown into metabolic intermediates and release of reducing power oxidative or reductive?

#NAME?

22

What is the result of breakdown into metabolic intermediates and release of reducing power being oxidative?

It requires coenzymes

23

What happens to to coenzymes used in breakdown into metabolic intermediates and release of reducing power after?

They are reduced

24

Is energy produced during breakdown into metabolic intermediates and release of reducing power?

A small proportion is

25

How is ATP produced during breakdown into metabolic intermediates and release of reducing power?

Direct phosphorylation of ADP to ATP

26

What bonds are broken in breakdown into metabolic intermediates and release of reducing power?

C-C

27

Where does the TCA occur?

In the mitochondria

28

Is the TCA oxidative or reductive?

#NAME?

29

What is the result of TCA being oxidative?

It requires NAD + and FAD

30

Is energy produced in the TCA cycle?

A small proportion is produced directly

31

What happens to acetyl in the TCA cycle?

It is converted to 2CO 2

32

What has happened in the conversion of acetyl to 2CO 2 ?

Carbon has been oxidised

33

What happens to the CO 2 produced in the TCA cycle?

It is put back in circulation, then breathed out at lungs

34

What does the TCA produce?

Precursors for biosynthesis

35

What is the advantage of the TCA producing intermediates?

It’s a way of interconnecting pathways

36

Where does oxidative phosphorylation occur?

In the mitochondria

37

What happens in oxidative phosphorylation?

Electron transport and ATP synthesis

38

What happens to NADH and FADH 2 in oxidative phosphorylation?

They are re-oxidised

39

Why are NADH and FADH 2 re-oxidised in oxidative phosphorylation?

The energy within them in used to drive ATP synthesis

40

What is required for oxidative phosphorylation?

Oxygen

41

What happens to oxygen in oxidative phosphorylation?

It is reduced to H 2 O

42

Why is O 2 reduced in oxidative phosphorylation?

Needed to oxidise H carriers

43

Does oxidative phosphorylation produce energy?

Yes, large amounts of ATP are produced

44

What is the general formula of carbohydrates?

(CH 2 O) n

45

What are the two types of sugars?

- Aldose 
- Ketose

46

What is an aldose sugar?

One that contains a aldehyde group

47

What is a ketose sugar?

One that contains a ketogroup

48

Are sugars hydrophilic or hydrophobic in nature?

Quite hydrophilic

49

Why are sugars quite hydrophilic in nature?

They have multiple -OH groups

50

What is a monosaccharide?

A single unit

51

How many C’s are in a monosaccharide?

03-Sep

52

What is a triose sugar?

A 3 carbon sugar

53

What is a pentose sugar?

A 5 carbon sugar

54

What is a hexose sugar?

A 6 carbon sugar

55

How do monosaccharides with more than 5 carbons generally exist?

In a ring structure

56

Why do monosaccharides with more than 5 C atoms generally exist in a ring structure?

Because keto/aldehyde group at one end comes round and interacts with the other end, which cyclises the molecule

57

What reaction is occurring when a ring is formed in a sugar?

Carbonyl reacts with alcohol group

58

Give 3 features of hydrophilic molecules

- Attract water
- Water soluble 
- Don’t pass across the cell membrane without transporters

59

What is meant by sugars being partially oxidised?

They have H on them

60

What is the result of sugars being partially oxidised?

They need less oxygen than fatty acids for complete oxidation

61

What is a disaccharide

A molecule composed of two monosaccharides

62

What is oligosaccharide?

A molecule with 3-12 monosaccharides

63

Give an example of a group of oligosaccharides

Dextrins

64

What are polysaccharides?

Molecules with 10-100 monosaccharide units

65

What kind of bond is formed between monosaccharides?

O-glycosidic bond

66

What happens when an O-glycosidic bond is formed?

Water is eliminated

67

What are the two kinds of O-glycosidic bonds?

#NAME?

68

What is the difference between alpha and beta glycosidic bonds?

The alpha bond sticks up, and the beta bond goes down

69

Why is wether you have an alpha or beta glycosidic bond important?

Because enzyme function depends on bond type

70

What is the main storage polysaccharide in animals?

Glycogen

71

Where is glycogen stored?

Liver and muscles

72

What is the purpose of glycogen?

It is a rapidly mobilisable energy store

73

What bonds are found in glycogen?

- Alpha 1-4
- Alpha 1-6

74

Why are the two different bond types in glycogen?

It produces branches

75

How are glucose molecules organised in glycogen?

They are largely lined up end on end

76

Why is glycogen used as the store, not glucose?

Takes highly osmotic glucose effectively out of the solution

77

What is the main glucose polymer in plants?

Starch

78

What is starch made up of?

A mixture of amylose and amylopectin

79

What is the bond type in amylose?

Alpha 1-4

80

What are the bond types in amylopectin?

- Alpha 1-4
- Alpha 1-6

81

How does starch differ from glycogen?

Less highly branched

82

What is starch broken down into in the GI tract?

#NAME?

83

What is cellulose?

A structural glucose polymer in plants

84

What bonds are present in cellulose?

Beta 1-4

85

What is the difference between beta 1-4 and alpha 1-4 linkages?

Beta are more stable

86

Why can’t cellulose be digested?

There are no GI enzymes to digest ß1-4

87

What is cellulose important for?

GI function

88

Why is cellulose important for GI function?

Provides substrate for other molecules to stick to, to be acted on my other enzymes

89

What is the body content of dietary carbohydrate?

1%

90

Other than dietary, what are the other sources of carbohydrate?

It can be synthesised from amino acids

91

Where does carbohydrate digestion occur?

GI tract (extracellular)

92

What happens in the digestion of carbohydrate?

Hydrolysis of glycosidic bonds

93

Give 3 places that produce enzymes that are required for carbohydrate digestion

- Salivary glands 
- Pancreas 
- Small intestine

94

What enzyme is present in saliva?

Amylase

95

What does amylase do?

Breaks down starch and glycogen into dextrins by cleaving alpha1-4 glycosidic bonds

96

What enzyme for carbohydrate digestion does the pancreas produce?

Amylase

97

Is pancreatic amylase the same as salivary amylase?

No, but has same function

98

What does pancreatic amylase do?

Breaks carbohydrates down into monosaccharides

99

What enzymes for carbohydrate digestion does the small intestine have?

It has the disaccharidases lactase, sucrase, pancreatic amylase and isomaltase

100

Where are the enzymes in the small intestine?

Attached to the brush border membrane of epithelial cells

101

What does lactase break down?

Lactose

102

What does sucrase break down?

Sucrose

103

What does isomaltase break down?

Alpha1-6 branches

104

What happens in absorption?

Active transport into intestinal epithelial cells

105

How do monosaccharides get to the target tissues?

Via the blood supply

106

Why does absorption need active transport?

Because the concentration in the cells is greater than that in the lumen

107

How is glucose uptaken into the cells?

Facilitated diffusion

108

What allows facilitated diffusion of glucose?

The transport proteins GLUT1-GLUT5

109

What is the difference between each GLUT?

They have different tissue distribution and affinities

110

How can GLUT transporters be controlled?

Hormonally

111

Which cells can metabolise glucose?

All

112

Why can all cells metabolise glucose?

They all have the glycolytic pathway

113

Which tissues have an absolute requirement for glucose?

- RBC
- WBC
- Kidney medulla 
- Lens of eye

114

What does the uptake of glucose to tissues with an absolute glucose requirement depend on?

The concentration of glucose in the blood

115

When are obligate glucose uses susceptible?

In starvation

116

What happens in starvation conditions?

The body goes to great lengths to maintain glucose in these tissues, so they have a continuing substrate supply

117

What tissues prefer glucose as their substrate supply?

CNS (brain) 
However, they are not obligated

118

Which tissues need glucose for specialised functions?

#NAME?

119

Why do the liver and adipose tissue require glucose for specialised functions?

They require carbohydrate backbone for more complex lipid molecule synthesis

120

What is the central pathway in CHO metabolism?

Glycolysis

121

Where does glycolysis occur?

In the cytoplasm of all cells

122

What are the functions of glycolysis?

- Oxidise glucose
- NADH (reducing equiv.) production
- Synthesis of ATP from ADP
- Produce C 3 and C 6 intermediates

123

Is glycolysis exergonic or endergonic?

Exergonic

124

Is glycolysis oxidative or reductive?

Oxidative

125

Is there any loss of C in glycolysis?

No, it’s just cut in half

126

Can glycolysis operate anaerobically?

Yes, with one additional enzyme

127

When will glycolysis need to operate anaerobically?

When blood supply does not keep up with metabolic need for O 2

128

Give the overall equation for glycolysis

Glucose (C6) + 2Pi + 2ADP + 2NAD +   →    2 Pyruvate (C3) + 2ATP + 2NADH + 2H + + 2H 2 O

129

What is required for each step of the glycolytic pathway?

Specific enzymes

130

What is the first step of glycolysis?

Phosphorylation of glucose to form glucose-6-phosphate

131

What happens in the phosphorylation of glucose?

Phosphate is transferred from ATP to glucose

132

Why does glucose need to be phosphorylated in glycolysis?

It needs to be activated, otherwise glucose is a stable molecule

133

What is the result of the phosphorylation of glucose?

#NAME?

134

How much ATP does step 1 of glycolysis use?

2 moles per mole of glucose

135

What happens in step 2 of glycolysis?

Isomerisation- G-6-P is rearranged to form fructose-6-P

136

What happens in step 3 of glycolysis?

F-6-P phosphorylated to form F-1,6-bisP

137

What is the purpose of the phosphorylation of F-6-P?

It activates the molecule, so it becomes much more energetic

138

Which steps in phase 1 of glycolysis (steps 1-3) are committing?

1 and 3

139

Why are steps 1 and 3 of glycolysis committing?

They have a large negative ∆G

140

At what step is glucose committed to metabolism via glycolysis?

3

141

What is the result of step 3 committing glucose to metabolism by glycolysis?

It can be used as a regulatory step

142

What happens in reaction 4 of glycolysis?

Cleavage of C 6 to C 3

143

What is formed in the cleavage of C 6 to C 3 ?

DHAP and G-3-P

144

What is reaction 5 of glycolysis

DHAP ↔ G-3-P

145

What happens in reaction 6 of glycolysis?

A small amount of reducing power is captured in NADH

146

How is reducing power captured in reaction 6 of glycolysis?

By coupling to oxidation reactions

147

What happens in reaction 7-10 of glycolysis?

ATP synthesis

148

Why can ATP synthesis occur in stages 7-10 in glycolysis?

Because the molecules are now energetic enough to give up energy

149

What kind of phosphorylation occurs in steps 7-10 of glycolysis?

Substrate level phosphorylation

150

How does substrate level phosphorylation occur in steps 7-10 of glycolysis?

1,3-BPG and ADP are bought together in an enzymes active site, where direct phosphate transfer occurs

151

Which reaction of 7-10 of glycolysis is irreversible?

10

152

Why is reaction 10 of glycolysis irreversible?

Because it has a large negative ∆G

153

What does the body want to do in times of starvation?

Make glucose

154

What can be used to make glucose in times of starvation?

Some of the enzymes in the glycolytic enzymes

155

What must be done to use the glycolytic pathway to produce glucose?

Must find ways of bypassing steps 1,3 and 10

156

Why must steps 1, 3 and 10 by bypassed when making glucose using the glycolytic pathway?

Because the reactions are so energetically committed

157

How much ATP is synthesised during glycolysis?

Net 2 moles of ATP per mole of glucose- 2 moles are invested to get it going, and 4 moles are produced per mole of glucose (C 3 x 2)

158

Why does glycolysis occur in small steps?

- Chemistry easier in small steps 
- Efficient energy conversion
- Gives versatility 
- Can be controlled

159

Why does smaller steps mean more efficient energy conversion?

If large, complex molecules used, more energy is wasted as heat

160

Why does smaller steps give more versatility in glycolysis?

#NAME?

161

Where is DHAP formed in glycolysis?

In step 4, when C 6 is cleaved into 2 x C 3 , one of which is DHAP

162

What is DHAP converted into?

Glycerol phosphate

163

Give the equation for the conversion of DHAP to glycerol phosphate

DHAP + NADH → Glycerol Phospate + NAD +

164

What enzyme is required for the conversion of DHAP to glycerol phosphate?

Glycerol 3-phosphate dehydrogenase

165

What kind of molecule is glycerol phosphate?

A 3 carbon phosphorylated alcohol

166

Where is glycerol phosphate important?

In triglyceride and phospholipid biosynthesis

167

Why is glycerol phosphate important in triglyceride synthesis?

It forms the backbone

168

Where is glycerol phosphate produced?

- Adipose tissue 
- Liver

169

What is the result of DHAP being required for lipid synthesis in liver?

Lipid synthesis in liver requires glycolysis

170

Can the liver phosphorylate glycerol directly?

Yes

171

What is 1,3-bisphosphoglycerate converted into?

2,3-bisphosphoglycerate

172

What enzyme is required for the conversion of 1,3-BPG to 2,3-BPG?

Bisphosphoglycerate mutase

173

What can 2,3-BPG interact with?

Haemoglobin

174

Why can 2,3-BPG interact with haemoglobin?

Because it is negatively charged, so can interact with positive charges within haemoglobin

175

How is 2,3-BPG produced in red blood cells?

From 1,3-BPG

176

Why is 2,3-BPG important?

Important regulator of oxygen affinity in haemoglobin- produces the tense form

177

What concentration is 2,3-BPG present in red blood cells?

5mM- same as haemoglobin

178

What does transfusion blood contain to provide the 2,3-BPG required?

Glucose

179

How long can transfusion blood be kept for?

120 days

180

Why can transfusion blood only be kept for 120 days?

Any longer and the 2,3-BPG all gets metabolised

181

What are the 2 regulation methods for glycolysis?

#NAME?

182

How does metabolic regulation of glycolysis occur?

If high [NADH] (therefore low [NAD + ], signals high energy levels, which causes product inhibition at step 6, which thereby inhibits glycolysis

183

How does high [NADH] cause product inhibition at step 6 of glycolysis?

If the product of the enzyme is high, it will feed back into the equilibrium, pushing the reaction in the opposite direction

184

How does the product inhibition at step 6 cause an overall inhibition of glycolysis?

If glucose comes in at the top of the pathway, the whole pathway backs up because the concentration of substrates increases, which allows G-6-P to reach a concentration that means it’s fed into glycogen storage

185

Where would you not use regulation on enzymes?

In a reaction that comes to equilibrium

186

Why would you not put regulation on a reaction that comes to equilibrium?

It would still come to the same equilibrium, just reach it at a different rate, so no regulation

187

Which enzymes are potential sites of control in metabolic pathways?

Those catalysing essentially irreversible reactions

188

What are the two methods of enzymatic regulation in glycolysis?

#NAME?

189

What happens in allostery?

The activator/inhibitor binds at ‘another’ site

190

What two sites do proteins have?

- Catalytic site 
- Regulatory site

191

What happens at the catalytic site?

The substrate is converted to products

192

What happens at the regulatory site?

The binding of a specific regulatory molecule

193

What effect does the binding of a specific regulatory molecule have?

It can change the conformation of a protein, changing the catalytic activity

194

Does the binding of allosteric molecules have a inhibitory or activating effect?

Can be either

195

What happens in covalent modification of enzymes?

Phosphorylation or dephosphorylation

196

What enzymes are affected in the allosteric regulation of glycolysis?

#NAME?

197

How is hexokinase affected by allosteric inhibition?

Decreased by G-6-P

198

How does allosteric inhibition using hexokinase in glycolysis work?

Hexokinase has a second, allosteric site that recognises G-6-P, so when G-6-P levels increase, causes product inhibition.

199

What is the significance of phosphofructokinase-1?

It is the enzyme that is responsible for the committing step in glycolysis

200

How is phosphofructokinase-1 affected by allosteric regulation in the muscle?

It is decreased by high ATP:AMP ratio

201

How does allosteric activation using phosphofructokinase-1 in the muscle work?

The enzyme is stimulated by AMP as it binds as a positive allosteric regulator

202

What is the importance of AMP being a positive allosteric regulation on phosphofructokinase-1?

AMP is the low energy signal, as ATP is converted to ADP and AMP, so activates enzyme to make more energy when it’s low

203

What happens to phosphofructokinase-1 in times of high energy?

There is feedback inhibition from ATP, so negative feedback on committing enzyme

204

How is phosphofructokinase-1 affected by allosteric regulation in the liver?

It is increased by high insulin:glucagon ratio

205

How is pyruvate kinase affected by allosteric regulation?

Increased by high insulin:glucagon

206

Why is pyruvate kinase increased by high insulin:glucagon

It tells the cell that there is lots of glucose present, so the high ratio means that the enzyme can be switched on to use the glucose

207

How is pyruvate kinase switched on?

Dephosphorylation

208

What would happen if NAD + was not regenerated from NADH produced during glycolysis?

Glycolysis would stop due to product inhibition at step 6

209

How many moles of NADH are produced per mole of glucose?

2

210

What is NAD + essential for?

The continuation of the glycolytic pathway

211

How does the cumulative level of NAD + and NADH change?

It doesn’t, it remains constant

212

When is NAD + usually regenerated from NADH?

In stage 4 of metabolism

213

When can stage 4 of metabolism not occur?

#NAME?

214

Why can’t RBC’s regenerate NAD + from NADH?

Because they have no stage 3 and 4 of metabolism

215

Where is the oxygen supply often reduced?

To the gut and the muscles

216

How can NAD + be regenerated when stage 4 of metabolism cannot occur?

Using lactate dehydrogenase (LDH)

217

Give the equation for the regeneration of NAD +  using LDH

NADH + H + + pyruvate  ↔  NAD +  + lactate

218

What is the problem with the regeneration of NAD +  using LDH?

It produces an acid

219

What must be done to the lactate?

It must be removed

220

Why must the lactate be removed?

Otherwise muscles would fatigue

221

Where is lactate predominantly produced?

#NAME?

222

What happens to the lactate produced in tissues?

It is released into blood

223

Where is lactate normally metabolised?

Liver and heart

224

How is lactate usually metabolised?

Using LDH, processed by the reverse reaction

225

What must happen in the liver and heart for efficient NAD +  regeneration?

Must be well supplied with oxygen

226

In what 3 ways is lactate utilised?

#NAME?

227

Give the equation for the conversion of lactate into pyruvate

NAD +  + lactate  →    NADH + H +  + pyruvate

228

Where is lactate used directly for energy production?

In the heart

229

How is lactate used directly for energy production in the heart?

Through the Krebs cycle and oxidative phosphorylation

230

What is the ultimate product from the use of lactate to produce energy directly?

CO 2

231

Where does the conversion of lactate to glucose occur?

The liver

232

What is the process of converting lactate to glucose called?

Gluconeogenesis

233

Give 4 situations where the conversion of lactate to glucose is impaired

- Liver disease
- Thiamine deficiency 
- Alcohol
- Enzyme deficiencies

234

Why is gluconeogenesis inhibited after alcohol?

Because alcohol is metabolised by alcohol dehydrogenase, which takes NAD +  and converts it to NADH, therefore NAD +  can’t be used for reconverting to lactate

235

How is lactate produced via pyruvate?

Using glucose and alanine

236

How much lactate is produced without major exercise?

40-50g per 24hrs

237

How much lactate is produced with strenuous exercise?

30g within 5mins

238

What can lactate production in pathological situations lead too?

Shock or congestive heart failure

239

When may pathological lactate production occur?

When circulation is compromised to normally oxygenated tissues

240

What 3 factors determine the plasma concentration of lactate?

- Production 
- Utilisation 
- Kidneys

241

Which tissues utilise lactate

Liver, heart and muscle

242

What disposes of lactate?

Kidneys

243

At what plasma concentration of lactate would a patient have hyperlactaemia?

2-5mM

244

Is hyperlactaemia above or below the renal threshold?

Below

245

Does hyperlactaemia cause a change in blood pH?

No

246

Why does hyperlactaemia not cause a change in blood pH?

Because there is sufficient circulating protein to buffer blood pH

247

At what plasma concentration of lactate would a patient have lactic acidosis?

Above 5mM

248

Is lactic acidosis above or below the renal threshold?

Above

249

What happens to the blood pH in lactic acidosis?

It decreases

250

What is fructose converted to in the body?

2 molecules of G-3-P

251

What is galactose converted to in the body?

G-1-P, then to G-6-P, then G-3-P

252

What happens to all carbohydrate in the diet?

It ultimately goes to glycolysis to be metabolised

253

Where does fructose in the diet come from?

Cane/beet sugar

254

What is sucrose a disaccharide of?

Fructose + glucose

255

Where is fructose metabolised?

In liver

256

What kind of enzymes metabolise fructose?

Soluble

257

Describe the metabolism of fructose

- Fructose converted into fructose-1-P, through the action of fructokinase. Requires ATP
- Fructose-1-P is converted into 2-glyceraldehyde-3-P, by action of aldolase. 
- 2-glyceraldehyde-3-P goes into glycolysis

258

What conditions can arise from errors in fructose metabolism?

- Essential fructosuria 
- Fructose intolerance

259

What is missing in essential fructosuria?

Fructokinase

260

What happens in essential fructosuria?

Fructose levels build in circulation, rising to a level that is greater than the renal threshold

261

What is the clinical presentation of essential fructosuria?

Fructose in urine, but no clinical signs

262

What is missing in fructose intolerance?

Aldose

263

What happens to fructose metabolism in fructose intolerance?

Fructose can feed into the pathway and form F-1-P, but this cannot be metabolised, causing accumulation in the liver

264

What is the result of the accumulation of F-1-P in the liver?

Causes liver damage

265

What is the treatment for fructose intolerance?

Remove fructose from diet

266

Where does galactose come from?

Milk

267

What is lactose a disaccharide of?

Glucose + galactose

268

Where is galactose metabolised?

Liver

269

Describe the metabolism of galactose

- Galactose is converted into galactose-1-P, by action of galactokinase. This requires ATP.
- Galactose-1-P is converted into glucose-1-P, by action of galactose-1-P uridyl transferase. This reaction also causes conversion of UDP-glucose to UDP-galactose, by action of UDP-galactose 4’-epimerase
- Glucose-1-P goes into glycolysis

270

What does UDP-galactose 4’-epimerase do?

Mutagensies galactose to glucose by moving hydroxyl groups around

271

What is the role of UDP-glucose in galactose metabolism?

It acts catalytically

272

What is the clinical importance of galactose metabolism?

Galactosaemia

273

What can cause an inability to utilise galactose?

- Galactokinase deficiency 
- Transferase deficiency

274

Is galactokinase deficiency rare or common?

Rare

275

What happens in galactokinase deficiency?

Galactose accummulates

276

Is transferase deficiency rare or common?

Common

277

What happens in transferase deficiency?

Galactose and galactose-1-P accumulate

278

What happens when galactose levels rise?

Can reach concentrations that enter enzymes that have low Km for galactose, and therefore wouldn’t normally metabolise galactose

279

Give an example that only metabolises galactose when it’s concentrations get too high

Aldose reductase

280

Give the equation for the effect of aldose reductase on galactose

Galactose + NADPH  →    Galactitol + NADP +

281

What is the result of the depletion of NADPH levels?

It damages structures

282

Why does NADPH depletion cause structure damage?

It prevents maintenance of sulphydryl groups on proteins, leading to inappropriate disulphide bond formation

283

What is the result of the inappropriate formation of disulphide bonds?

The loss of structural and functional integrity of some proteins that depend on free -SH groups

284

What can happen to proteins that rely on free -SH groups?

Protein clumping and damage to cells

285

Give a specific example of problems caused by failure to maintain free -SH groups

In the lens of the eye

286

What happens in the lens of the eye when free -SH groups not maintained?

Get inappropriate cross linking in the eye, leading to cataracts

287

What organs does the accumulation of galactose-1-P affect?

Kidneys, liver and brain

288

When does the pentose phosphate pathway run?

When energy levels are high

289

Why does the pentose phosphate level only run when energy levels are high?

If glycolysis is running, ATP and NADH levels are high, so there is product inhibition and allosteric inhibition of glycolysis. This causes G-6-P levels to rise, and so can enter pathways it wouldn’t otherwise enter as the enzymes Km is too high- the pentose phosphate pathway

290

Where does the pentose phosphate pathway occur?

In the cytoplasm

291

How many stages are there in the pentose phosphate pathway?

2

292

What are the two stages in the pentose phosphate pathway?

- Oxidative decarboxylation 
- Rearrangement to glycolytic intermediates

293

Give the equation for the oxidative decarboxylation stage of the pentose phosphate pathway

Glucose-6-phosphate + NADP +  →    C 5 + CO 2 + NADPH

294

What enzyme is used in the conversion of G-6-P to C 5 ?

Glucose-6-P dehydrogenase

295

Give the equation for the arrangement to glycolytic intermediates step in the pentose phosphate pathway

3C 5 -sugars  →    2 fructose-6-P + glyceraldehyde-3-P

296

What can happen to glyceraldehyde-3-P?

It can go back into glycolysis

297

Is the pentose phosphate reversible or irreversible?

Irreversible

298

Why is the pentose phosphate pathway irreversible?

Because CO 2 is lost

299

What is the pentose phosphate pathway controlled by?

NADP + /NADPH ratio

300

How is the pentose phosphate pathway controlled by the NADP + /NADPH ratio?

If NADP + /NADPH ratio high, less NADPH substrate for pathway to run

301

What are the functions of the pentose phosphate pathway?

- Produce NADPH in cytoplasm
- Produce C 5 sugars

302

What is NADPH in the cytoplasm needed for?

#NAME?

303

Give in example of where biosynthetic reducing power is needed

Lipid synthesis

304

Where is there a high level of lipid synthesis

In liver and adipose tissue

305

What does the maintenance of free -SH groups on certain proteins prevent?

Oxidation to -S-S- (disulphide) bonds

306

What are C 5 sugars needed for?

Nucleic acid synthesis

307

What tissues have high levels of nucleic acid synthesis?

Ones that divide a lot, e.g. bone marrow

308

What is the result of a G-6-P dehydrogenase deficiency?

Means that G-6-P can’t be converted into 5 sugar phosphate, therefore no pentose phosphate pathway and no NADPH produced by this pathway

309

Is G6PDH deficiency common or rare?

Common

310

What is the result of G6PDH deficiency in RBCs?

The decreased NADPH results in disulphide bonds being formed , which means that haemoglobin is not kept in the reduced form, leading to aggregated proteins called Heinz bodies, which leads to haemolysis, causing anaemia

311

What is the effect of G6PDH deficiency in the lens of eye?

Get clouding due to inappropriate disulphide bond formation

312

What must happen to pyruvate at the end of stage 2 of respiration?

It must be acted on my pyruvate dehydrogenase

313

What is added to pyruvate when it’s acted upon by pyruvate dehydrogenase?

CoA

314

Give the equation for the reaction between pyruvate and CoA

Pyruvate + CoA + NAD +  →    acetyl CoA + NADH + H +

315

What is CoA?

A molecule that, when bonded to another molecule, puts in a reactive bond, therefore activating it

316

Where is PDH found in the cell?

In the mitochondria

317

Where does the PDH reaction occur?

In the mitochondrial matrix

318

How is pyruvate bought into the mitochondrial matrix?

Transported across mitochondrial membrane on a protein

319

Why does pyruvate need to be transported into the mitochondrial matrix on a protein?

Because it is hydrophilic

320

How many enzymes are in the PDH complex?

5

321

How is the PDH complex arranged

Neatly, so that substrates and products are passed around the complex

322

What do different enzyme activities require?

Various cofactors

323

Give 4 cofactors that enzymes in the PDH complex requires

#NAME?

324

What provide the cofactors that the PDH complex requires?

B vitamins

325

What is the result of B vitamins providing the cofactors required for the PDH complex?

The reaction is sensitive to B1 deficiency

326

Is the PDH reaction reversible or irreversible?

Irreversible

327

Why is the PDH reaction irreversible?

Because it produces CO 2

328

What is the result of the PDH reaction being irreversible?

It is a key regulatory step

329

Can pyruvate be formed from acetyl-CoA?

No

330

What is the PDH reaction activated by?

#NAME?

331

Give 5 low energy signals that activate the PDH reaction

#NAME?

332

What is the PDH reaction inhibited by?

- High energy signals 
- Phosphorylation

333

Give 4 high energy signals that inhibit the PDH reaction

#NAME?

334

What does a PDH deficiency result in?

Lactic acidosis

335

How does PDH deficiency cause lactic acidosis?

If the PDH reaction goes wrong, can’t pass substrate into the TCA cycle, so pyruvate builds up, which is then converted into lactic acid by lactate dehydrogenase, which causes lactic acidosis

336

Where does the TCA cycle occur?

In the mitochondria

337

Is the TCA cycle a single pathway, or multiple pathways?

A single pathway

338

What is converted into what in the TCA cycle?

Acetyl (CH 3 CO - ) to 2CO 2

339

Is the TCA cycle oxidative or reductive?

Oxidative

340

What does the TCA cycle require as it is oxidative?

NAD + and FAD

341

Is energy produced in the TCA cycle?

Some, in the form of ATP and GTP

342

How is ATP and GTP produced in the TCA cycle?

Substrate level phosphorylation

343

Other than energy, what else does the TCA cycle produce?

Precursors for biosynthesis

344

What are the key steps in the Krebs cycle?

The oxidative steps, where substrate level phosphorylation occurs, and where CO 2 is released

345

What has happened to all the reducing power on the original glucose molecule by the end of the TCA cycle?

It has been captured

346

How is the reducing power of glucose captured in the TCA cycle?

- Substrate level phosphorylation 
- On reducing carriers

347

What is the overall equation for the TCA cycle?

CH 3 CO~CoA + 3NAD + + FAD + GDP + Pi + 2 H 2 O  →    2CO 2 + CoA + 3NADH +FADH 2 + GTP

348

What is the overall yield per mole of glucose from the TCA cycle?

6 NADH
2 FADH 2
2 GTP

349

How is the TCA cycle regulated?

- By energy availability 
- By irreversible steps

350

What ratios regulate the TCA cycle by energy availability?

- ATP/ADP
- NADPH/NADP +

351

What steps in the TCA cycle are irreversible?

Ones where CO 2 is removed

352

In what reactions in the TCA cycle is CO 2  removed?

- Isocitrate + NAD +  →    α-ketoglutarate (C5) + CO 2 + NADH
- CoA + α-ketoglutarate (C5) + NAD +  → succinyl-CoA (C4) + CO 2 + NADH

353

What is the enzyme for the conversion of isocitrate to α-ketoglutarate?

Isocitrate dehydrogenase

354

What is isocitrate dehydrogenase regulated by?

- Positively regulated by ADP 
- Negatively regulated by ATP and NADH

355

What is the result of isocitrate dehydrogenase being stimulated by ADP?

If energy levels are low, then it’s stimulated into activity

356

What is the enzyme of the conversion of α-ketoglutarate to succinyl-CoA?

α-ketoglutarate dehydrogenase

357

What is α-ketoglutarate dehydrogenase inhibited by?

It’s product, NADH, and ATP

358

What 5 intermediates in the TCA cycle supply biosynthetic processes?

#NAME?

359

What biosynthetic processes does citrate supply?

Production of fatty acids

360

What biosynthetic processes does α-ketoglutarate supply?

Production of amino acids

361

What biosynthetic processes does succinate supply?

- Production of amino acids 
- Production of haem

362

What biosynthetic processes does malate supply?

Production of amino acids

363

What biosynthetic processes does oxaloacetate supply?

#NAME?

364

What is meant by the TCA being a hub?

It’s possible to feed in and out of pathway, and convert one thing into another

365

What is TCA in a central pathway in?

The catabolism of sugars, fatty acids, ketone bodies, amino acids and alcohol

366

What strategy does the TCA cycle use?

Produce molecules that readily lose CO 2

367

What bond is broken in the TCA cycle?

The C-C bond in acetate (acetyl~CoA)

368

What are carbons oxidised to in the TCA cycle?

CO 2

369

How many oxidative steps are there in the TCA cycle?

4

370

What do the oxidative steps in the TCA use?

3 using NAD + , 1 using FAD

371

Does the TCA cycle function in the absence of oxygen?

No

372

Why does the TCA cycle not function in the absence of oxygen?

NADH and FADH 2 being stripped off requires oxidative phosphorylation in mitochondria to be running. If there is no oxygen, there is a build up, so the cycle will stop

373

What happens when the TCA cycle can’t run due to lack of oxygen?

We must rely on the energy from glycolysis and lactate dehydrogenase

374

How do the intermediates of the TCA cycle act?

Catalytically

375

Why is it said that intermediates in the TCA act catalytically?

There is no net synthesis or degradation of the intermediates alone (unless if fed in from other substrates)

376

How much energy does substrate level phosphorylation release?

~124kJmol -1

377

Where is the remaining energy to be accounted for in a glucose molecule?

In the chemical bonds of NADH and FADH 2

378

How is the energy in NADH and FADH 2 released?

High energy electrons are transferred to oxygen, releasing large amounts of energy

379

What is the energy released from NADH and FADH 2 used to do?

Drive ATP synthesis

380

Where does stage 4 of catabolism occur?

In the mitochondria

381

What happens in stage 4 of catabolism?

Electron transport and ATP synthesis

382

What happens to NADH and FADH 2 in stage 4 of catabolism?

They’re reoxidised

383

What is the purpose of the reoxidation of NADH and FADH 2 in catabolism?

It uses the bond energy released to produce ATP

384

Why is O 2 required in stage 4 of catabolism?

It picks up electrons released from reduced carriers

385

What happens to oxygen in stage 4 of catabolism?

It is reduced to H 2 O

386

Is ATP produced in stage 4 of catabolism?

Yes, large amounts

387

What processes occur in stage 4 of catabolism?

#NAME?

388

What happens in electron transport?

Electrons on NADH AND FADH 2  are transferred through series of carrier molecules to oxygen

389

What is the purpose of electron transport?

It releases energy in steps

390

Why does electron transport release energy in steps?

It allows control of the process, so the most can be got out of it

391

What happens in oxidative phosphorylation?

Free energy is used to drive ATP synthesis

392

Describe the structure of a mitochondrion?

- Have outer membrane and inner membrane, folded into cristae 
- Between membranes is intermembrane space
- Inside membranes is matrix

393

Are the mitochondrial membranes permeable?

- The outer membrane is quite leaky 
- The inner membrane is very impermeable

394

What is the inner membrane especially impermeable too?

Hydrogen ions

395

What does the inner mitochondrial membrane contain?

All machinery for electron transport

396

What is the significance of proton translocating complexes (PTC) in electron transport?

In a number of steps, electrons are passed between electron transport complexes, with a bit of energy being given up each time

397

What happens at proton translocating complex (PTC) 1 in electron transport?

NADH gives up an electron to electron transport

398

Give the equation for what happens at PTC 1

NADH + H +  → NAD +

399

What happens in the mitochondrial membrane once NADH has given up it’s electrons at PTC 1?

2e - pass down as energy level in inner mitochondrial membrane, and 2 H + are pushed out to inter membrane space

400

What happens at PTC 2?

FAD feeds in

401

Why does FAD have a lower energy yield?

Because it feeds in halfway down transport chain, so only get 4 H + ions out of inter membrane space

402

What happens at PTC 3?

2 H + are fed in from matrix, 2e - move down and 2 H + are pushed out

403

What happens at the end of the electron transport chain?

2H + + O combine with the 2 e - from the inner mitochondrial membrane, on the mitochondrial matrix, forming water

404

What are electrons transferred through in the electron transport chain?

A series of carrier molecules

405

Where are the carrier molecules electrons are transferred through mostly found?

Within proteins

406

How much of the energy is used to move H + across the membrane?

~30%

407

How is a lot of energy lost in the electron transport chain?

As heat

408

Why is it important that some energy is lost as heat in the ETC?

To maintain body heat

409

What is meant by membrane potential?

The [H + ] gradient across the inner membrane of mitochondria

410

What does the membrane potential create?

Proton motive force

411

How is the proton motive force induced?

Every time you transfer positive ion out of the matrix, negative anion must be left behind, generating an electrical potential across the membrane, creating a driving force on hydrogen ions that want to come back into matrix

412

What gradients are now supporting hydrogen ions wanting to come back into the matrix?

#NAME?

413

What does the proton motive force create?

Stored up potential energy

414

Give the reaction that proton translocating ATPase catalyses

ATP + 2H + (mitochondrial matrix)  ↔ ADP + Pi + 2H + (cytoplasm)

415

What is the energy released by proton translocating ATPase used to do?

Drive H ions out into the inner membrane space

416

Is the proton translocating ATPase reaction reversible or irreversible?

Reversible

417

What is the result of the proton translocating ATPase reaction being reversible?

The gradient of H ions set up by electron transport can be used, if we allow H ions to run back into the matrix down their electrochemical gradient, releasing energy

418

What can the energy released when hydrogen ions come back in through proton translocating ATPase be used for?

To drive synthesis of ATP

419

Why is the proton gradient created effectively doing oxidative phosphorylation?

Because the products of oxidation are driving the phosphorylation of ATP from ADP using the proton gradient between two mitochondrial membranes, as the return is highly energetically favourable

420

What is energetically favoured by the electrochemical potential?

Return of protons across the membrane, from the inner mitochondrial space to the matrix

421

What is the only way protons can return across the membrane to the matrix?

Via the ATP synthase

422

Why can protons only return across the membrane through ATP synthase?

Due to the impermeability of the inner mitochondrial membrane

423

What is the result of protons only being able to return through ATP synthase?

It drives ATP synthesis

424

What is ATP synthesis coupled to?

Electron transport

425

How is electron transport coupled to ATP synthesis?

Electrons are transferred from NADH and FADH 2 to molecular oxygen, releasing energy to generate the p.m.f. Energy from the dissipation of p.m.f. is coupled to synthesis of ATP from ADP, further capturing the energy

426

How many PTC’s does NADH use?

3

427

How many PTC’s does FADH 2  use?

2

428

Why does NADH use more PTCs than FADH 2 ?

Because electrons in NADH have more energy

429

What is the result on p.m.f. of NADH having more energy than FADH 2 ?

More p.m.f. from NADH

430

What does a greater p.m.f. mean for ATP synthesis?

More ATP synthesised

431

How is oxidative phosphorylation regulated by ADP?

When [ADP] decreases, no substrate for ATP synthesis, so the inward flow of H + stops. This leads to an increase in [H + ] in the intermitochondrial space, which prevents further H + pumping, stopping electron transport. As electron transport and oxidative phosphorylation are tightly coupled, this inhibits both

432

Give an example of an inhibitor of electron transport (other than ADP)

Cyanide

433

How do inhibitors such as cyanide block electron transport?

By preventing acceptance of electrons by oxygen

434

What happens when an inhibitor blocks the acceptance of electrons by oxygen?

The flow of electrons ceases, which means there is no p.m.f. and therefore no oxidative phosphorylation

435

What structures are electron carriers similar to?

That of haem

436

What is the result of electron carriers using a similar structure to that of haem?

CO can inhibit

437

Why can CO inhibit electron carriers?

It binds with a higher affinity that oxygen

438

What affect does cyanide have on electron transport?

It blocks electron acceptance by oxygen, therefore causing a build up of electrons, so no energy is given up to put H + in inner membrane space, and so decreasing the p.m.f. and consequently ATP.

439

What do uncouplers do?

Increase the permeability of mitochondrial inner membrane to protons

440

What is the result of the increased permeability of the inner membrane to protons?

Won’t have to go through ATP synthase

441

What happens to the p.m.f. because of uncouplers?

Reduces it

442

Why do uncouplers reduce the p.m.f.?

Because it dissipates the proton gradient

443

In the presence of uncouplers, what happens to the energy instead of it driving ATP synthesis?

It is released as heat instead

444

Does electron transport continue when uncoupling has occurred?

Yes

445

Why does electron transport continue even after uncoupling?

Because there is no inhibition

446

Give 3 examples of things that can act as uncouplers

#NAME?

447

What are ox/phos diseases?

Generic defects in proteins encoded by mtDNA

448

What proteins encoded for by mtDNA are defective in ox/phos diseases?

Some sub-units of the PTC and ATP synthase

449

What is the result of the defective proteins in ox/phos diseases?

Decreased electron transport and ATP synthesis

450

What is the result of inefficiency in coupling?

Energy lost as heat

451

What does efficiency of coupling depend on?

Tightness of coupling

452

Where can the tightness of coupling be varied?

Brown adipose tissue

453

What is the degree of coupling controlled by in brown adipose tissue?

Fatty acids

454

What does the control of coupling in brown adipose tissue allow for?

Extra heat generation

455

What does brown adipose tissue contain?

Thermogenin (UCP1)

456

What is UCP1?

A naturally occurring uncoupling protein

457

What happens in response to cold?

Noradrenaline activates lipase and fatty acid oxidation

458

What is the affect of lipase oxidation?

It released fatty acids from triacylglycerol

459

What does fatty acid oxidation produce?

NADH and FADH 2

460

What happens to the NADH and FADH 2 released by fatty acid oxidation?

They go into electron transport

461

What do fatty acids activate?

UCP1

462

What does UCP1 do?

Transports H + back into the mitochondria

463

What happens when UCP1 transports H + back into the mitochondria?

#NAME?

464

Where is brown adipose tissue found?

#NAME?

465

Why is brown adipose tissue found in newborn infants?

To maintain heat, particularly around vital organs

466

Why is the extra heat from brown adipose tissue needed in newborn infants?

Because they have a small SA to volume ratio

467

What is the difference in requirements for oxidative and substrate level phosphorylation?

- Oxidative requires membrane-assoicated complexes 
- Substrate level requires soluble enzymes

468

What is the difference between methods of energy production in oxidative and substrate level phosphorylation?

- In oxidative, energy coupling occurs indirectly through the generation and subsequent utilisation of a proton gradient 
- In substrate level, energy coupling occurs directly, through formation of high energy hydrolysis bond (phosphoryl-group transfer)

469

What is the difference in oxygen requirement between oxidative and substrate level phosphorylation?

#NAME?

470

What is the difference in significance of amount of ATP produced between oxidative and substrate level phosphorylation?

- Oxidative is major ATP synthesis process in cells 
- Substrate level is minor process for ATP synthesis

471

When is substrate level phosphorylation the major process for ATP synthesis?

#NAME?