Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

My ESA1 > Metabolism S3 - Energy Production in Carbohydrates > Flashcards

Metabolism S3 - Energy Production in Carbohydrates Flashcards

1
Q

What is the equation for glycerol phosphate formation?

A

Dihydroxyacetone phosphate (DHAP) –> glycerol phosphate Glycerol 3-phosphate dehydrogenase enzyme NADH -> NAD+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is 2,3-BPG?

A

Important glycolysis intermediate. Produced from 1,3-BPG in RBC. Important regulator of O2 affinity of haemoglobin (tense state). Present in RBCs at same molar concentration as haemoglobin (~5mM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the formula for 2,3-BPG formation?

A

1,3-bisphosphoglycerate 2,3-bisphosphoglycerate Bisphospoglycerate mutase enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the metabolic regulation of glycolysis

A
  • High NADH concentration signals high energy levels i.e. low [NAD+] - Causes product inhibition of step 6 (1,3-BPG produced) - Inhibition of glycolysis due to availability of substrates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How may enzymes be regulated?

A
  • Flux through pathway regulated in response to the need - In metabolic pathways, enzymes catalysing essentially irreversible steps are potential sites of control 1. Allostery - activator binds at another site. Proteins with 2 sites: a. Catalytic site: substrate -> product b. Regulatory sites: binding of specific regulatory molecule. Affects catalytic activity. Can produce activation or inhibition. 2. Covalent modification (phosphorylation/dephosphorylation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe allosteric regulation of glucose

A
  • Step 1: Hexokinase decreased by G 6-P (product). Allosteric inhibitory site on hexokinase. - Step 3: Phosphofructokinase-1. Muscle: PFK-1 decreased by high ATP:AMP ratio. Allosteric. ATP binds to PFK-1 and reduces amount of substrate. Liver: PFK-1 increased by high insulin:glucagon. Dephosphorylation of enzyme by hormonal signals. - Step 10: Pyruvate kinase increased by high insulin:glucagon. Dephosphorylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What would happen if NAD+ wasn’t regenerated from NADH produced in glycolysis?

A

Glycolysis would stop due to product inhibition of step 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the oxidation/reduction of step 6

A
  • NAD+ linked, 2 moles of NADH produced per mole of glucose - Pathway needs NAD+ - Total NAD+ and NADH in cell is constant, therefore glycolysis would stop when all NAD+ is converted to NADH - Normally NAD+ regenerated from NADH in stage 4 of metabolism BUT - RBC have no stage 3 or 4 of metabolism - Stage 4 needs O2 - supply to muscles and gut often reduced - Therefore need to regenerate NAD+ by some other route: lactate dehydrogenase (LDH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the equation of the lactate dehydrogenase reaction?

A

NADH + H+ + pyruvate (CH3CO.COOH) NAD+ + lactate (CH3CHOH.COOH) LDH enzyme High levels of NADH and pyruvate NAD+ is oxidised

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the lactate dehydrogenase reaction

A
  • Lactate produced by RBC and skeletal muscle (skin, brain, GI) - Released into blood and normally metabolised by liver and heart via LDH (highly oxygenated tissues) - Lactate acidifies cells - Liver and heart need NAD+ to be regenerated efficiently, usually well supplied with oxygen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe lactate utilisation

A
  • Via pyruvate: NAD+ + lactate –> NADH + H+ + pyruvate LDH enzyme - Heart muscle -> CO2 - Liver -> glucose (gluconeogenesis): impaired in liver disease, thiamine vitamin deficiency, alcohol NAD+ -> NADH, enzyme deficiencies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is glycerol phosphate?

A

An important intermediate in glycolysis, to triglyceride and phospholipid biosynthesis. Produced from DHAP in adipose tissue and liver. Therefore lipid synthesis in liver requires glycolysis. N.B: liver can phosphorylate glycerol directly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe lactate production

A

Produced from glucose and alanine via pyruvate. - Without major exercise: 40-50g / 24hrs. RBC, skin, brain, skeletal muscle, GI tract. - Strenuous exercise (including hearty eating): 30g/5 min. Plasma levels double in 2-5 min. Back to normal by 90 min. Pathological situations e.g. shock, congestive heart disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is the plasma concentration of lactate determined?

A

By relative rates of: - Production - Utilisation (liver, heart, muscle) - Disposal (kidney)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the consequences of elevations of plasma lactate concentration?

A

Blood concentration normally constant below 1mM. - Hyperlactaemia: 2-5mM. Below renal threshold (not in urine). No change in blood pH (buffering capacity). - Lactic acidosis: above 5mM. Above renal threshold (in urine). Blood pH lowered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give an overview of the metabolism of galactose and fructose

A

See image

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is sucrose?

A

Fructose and glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Where does fructose metabolism occur?

A

In the liver (soluble enzymes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give an outline of fructose metabolism

A

Fructose –> Fructose-1-P –> 2-glyceraldehyde-3-P (enters glycolysis) 1st step: fructokinase enzyme, ATP -> ADP 2nd step: aldolase enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the clinical importance of fructose metabolism?

A
  • Essential fructosuria: fructokinase missing. Fructose in urine, no clinical signs. - Fructose intolerance: aldolase missing. Fructose and fructose-1-P accumulate in liver -> liver damage. Treatment = remove fructose from diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is fructose?

A

Cane/beet sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is galactose?

A

Milk sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is lactose?

A

Glucose and galactose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where does galactose metabolism occur?

A

In the liver (major tissue) - soluble enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Outline galactose metabolism

A

Galactose –> galactose 1-P –> glucose 1-P –> glycolysis 1st step: galactokinase enzyme. ATP -> ADP 2nd step: galactose-1-P uridyl transferase enzyme. UDP glucose UDP galactose (reverse reaction uses UDP-galactose 4’-epimerase enzyme) UDP glucose acts catalytically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is UDP-glucose?

A

Activated glucose. High energy bond to glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the clinical importance of galactose metabolism?

A

Galactosaemia - 1 in 30,000 births

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Give a brief overview of galactosaemia

A

Milk rich diet in infancy. Unable to utilise galactose. Problem as galactose enters other pathways. Depletes lens of NADPH -> structure damaged -> cataracts. Accumulation of galactose-1-P affects liver, kidney, brain. Treatment is a lactose-free diet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the two forms of galactosaemia?

A

Galactokinase deficiency (rare) - galactose accumulates Transferase deficiency (common) - galactose and galactose-1-P accumulate

30
Q

What is the formula for the reaction that occurs in galactosaemia?

A

Galactose –> Galactitol Aldose reductase enzyme NADPH –> NADP+

31
Q

Describe galactosaemia in detail

A

Raised galactose concentration enters new pathways. Depletes NADPH levels in lens. Prevents maintenance of free sulphydryl groups on protein-free cysteine R state - NADPH keeps them in reduced form. Inappropriate disulphide bond formation - cross-linking of proteins leads to precipitation out of solution. Loss of structural and functional integrity of some proteins that depend on free -SH groups e.g. lens of eye

32
Q

Outline the pentose phosphate pathway

A

Glucose -> G-6-P -> 5C sugar phosphatases (NADP+ -> NADPH, Co2 released - irreversible decarboxylation) —-> F-6-P OR G-3-P –glycolysis–> pyruvate lactate All enzymes in cytosol Two stage cytoplasmic pathway

33
Q

Give the two stages of the pentose phosphate pathway

A

A) Oxidative phosphorylation: Glucose-6-P —> C5 sugar + CO2. NADP+ –> NADPH. Enzyme is glucose-6-P dehydrogenase. B) Rearrangement to glycolysis intermediates. 3 C5 sugars —> 2 Fructose-6-P + glyceraldehyde-3-P. 1. No ATP produced. 2. Loss of CO2, so irreversible. 3. Controlled by NADP+/NADPH ratio at G-6-P dehydrogenase

34
Q

What are the functions of the pentose phosphate pathway?

A

1) Produces NADPH in cytoplasm a) Biosynthetic reducing power e.g. lipid synthesis therefore high activity in liver and adipose tissue. b) Maintain free -SH (cysteine) groups on certain proteins. Prevents oxidation to -S-S- (disulphide bonds), maintains structural integrity of proteins 2) Produce C5 sugar for nucleotides needed for nucleic acid synthesis. Therefore, high activity in dividing tissues e.g. bone marrow

35
Q

Describe what occurs in glucose-6-phosphate dehydrogenase (G6PDH) deficiency

A
  • Pentose phosphate pathway has an important role in providing NADPH to maintain SH group of proteins in a reduced state - Structural integrity and hence, functional activity of some proteins depends on free -SH groups. -G6PDH deficiency is a very common inherited defect - e.g. in RBC, decreased NADPH leads to disulphide bond formation, which leads to aggregated proteins - Heinz bodies - causing haemolysis (RBC breakdown) causing anaemia - In lens of eye, causes cataracts
36
Q

What happens at the end of stage 2?

A

Pyruvate does not enter directly into stage 3 (tricarboxylic acid cycle). Pyruvate dehydrogenase

37
Q

What is the reaction for pyruvate dehydrogenase (PDH)?

A

Stage 2 -> 3 CH3COCOOH (pyruvate) + CoA + NAD+ –> CH3CO~CoA (acetyl CoA) + CO2 + NADH + H+ Irreversible so key regulatory step Pyruvate cannot be formed from acetyl CoA Subject to multiple regulation

38
Q

Where does the PDH reaction occur?

A

Mitochondrial matrix - pyruvate transported from cytoplasm across mitochondrial membrane

39
Q

Describe pyruvate dehydrogenase (PDH)

A

A large multi-enzyme complex (5 enzymes). Different enzymes require various cofactors (FAD, thiamine pyrophosphate and lipoic acid). B-vitamins provide these factors, so reaction is sensitive to vitamin B1 deficiency (can’t process products of glycolysis)

40
Q

What does PDH deficiency lead to?

A

Lactic acidosis

41
Q

What are alternative names for the tricarboxylic acid (TCA) cycle?

A

Krebs cycle Citric acid cycle

42
Q

Where does the TCA cycle take place?

A

Mitochondria

43
Q

What does the TCA cycle produce?

A

Some energy (as ATP/GTP). Also produces precursors for biosynthesis

44
Q

What is the significance of oxaloacetate?

A

It is the start and end of the TCA cycle

45
Q

What forms of phosphorylation occur in the TCA cycle?

A

4 oxidative phosphorylation steps 1 substrate level phosphorylation step

46
Q

Give an overview of the TCA cycle

A
  • Other pathways feed in and out of this pathway - Single pathway - Acetyl (CH3CO-) converted to 2CO2 - Oxidative (requires NAD+, FAD) - All carbons that enter as glucose leave as CO2 - Central pathway for catabolism of sugars, fatty acids, ketone bodies, amino acids, alcohol - Strategy is to produce molecules that readily lose CO2 - Breaks C-C bond in acetate (acetyl~CoA) carbons oxidised to CO2 - Intermediates act catalytically - no net synthesis or degradation of TCA cycle intermediates alone
47
Q

What is the overall equation for one TCA cycle?

A

CH3CO~CoA + 3NAD+ + FAD + GTP + Pi + 2H2O –> 2CO2 + CoA + 3NADH + 3H+ +FADH2 + GTP

48
Q

What are the products of the TCA cycle from one glucose molecule?

A

Glucose –> 2 x 2C into TCA –> 6NADH + 2FADH2 + 2GTP

49
Q

Describe the regulation of the TCA cycle

A

By an irreversible step By energy availability e.g. ATP/ADP ratio and NADH/NAD+ ratio

50
Q

Describe regulation of TCA cycle by the isocitrate to alpha-ketoglutarate step

A
  • Isocitrate dehydrogenase enzyme - CO2 out - NAD+ (+ADP) –> NADH (-NADH, ATP) - Regulated by ADP when energy low
51
Q

Describe the regulation of the TCA cycle by the alpha-ketoglutarate to succinyl-CoA step

A
  • alpha-ketoglutarate dehydrogenase enzyme - CoA in - CO2 out - NAD+ –> NADH (- NADH, ATP, succinyl-CoA) - Inhibited by product
52
Q

Describe the ways in which the TCA cycle supplies biosynthetic processes

A

Releases energy and interconverts substrate molecules

53
Q

Give energy account for glycolysis and TCA cycle

A
  1. ATP from glycolysis -> (4ATP) 2ATP net (=-62kJmol^-1) TCA cycle -> 2GTP=2ATP (-62kJmol^-1) Total from substrate level phosphorylation = -124kJmol^-1 2. Still need to account for -2746kJmol^-1 3. Chemical bond energy of electrons in NADH and FADH2 4. High energy electrons in NADH and FADH2 transferred to oxygen with release of large amounts of energy - used to drive ATP synthesis
54
Q

Give an overview of catabolism stage 4 (oxidative phosphorylation)

A
  • Mitochondrial - Electron transport and ATP synthesis - NADH and FADH2 re-oxidised - O2 required (reduced to H2O) - Large amounts of energy (ATP) produced
55
Q

Describe the use of reducing power in ATP synthesis

A

Two processes: 1. Electrons on NADH and FADH2 transferred through a series of carrier molecules to oxygen (ELECTRON TRANSPORT). Releases energy in steps 2. Free energy released to drive ATP synthesis (OXIDATIVE PHOSPHORYLATION)

56
Q

Describe the membranes of a mitochondrion

A

Outer membrane is leaky Inner membrane is impermeable, especially to H+ ions

57
Q

Describe the final electron acceptor

A

Oxygen. Captures electrons on O2. Use to form H2O -> 6H+ total

58
Q

Describe electron transport

A
  • Electrons transferred through a series of carrier molecules (PTCs - protein translocating complexes, mostly within proteins), to O2, with release of energy - Approx 30% energy used to move H+ across membrane (a lot of energy is released as heat) - [H+] gradient (membrane potential) across inner mitochondrial membrane - positive relative to outside = proton motive force (pmf)
59
Q

Describe the role of proton translocating ATPase

A

Aka F1F0-ATPase or ATP synthase/synthetase ATP + 2H+(mitochondrial matrix) ADP + Pi + 2H+(cytoplasm) Reversible - becomes ATP synthesis

60
Q

Describe ATP synthesis

A
  • Return of protons is favoured energetically by the electrochemical potential (electrical and chemical gradient) - Protons can only return across membrane via ATP synthase and this drives ATP synthesis
61
Q

What is oxidative phosphorylation?

A

Electron transport coupled to ATP synthesis

62
Q

Describe oxidative phosphorylation

A
  • Electrons transferred from NADH to FADH2 to molecular oxygen - Energy released used to generate proton gradient: pmf - Energy from dissipation of proton motive force is coupled to synthesis of ATP from ADP
63
Q

Describe the difference in energy production of oxidative phosphorylation when NADH and FADH2 are used

A
  • Electrons in NADH have more energy than in FADH2, so NADH uses 3 PTCs, FADH2 uses only 2 - Greater pmf -> more ATP synthesised - Oxidation of 2 moles of NADH -> synthesis of 5 moles ATP - Oxidation of 2 moles of FADH2 -> synthesis of 3 moles ATP - So just NADH -> more energy
64
Q

Describe the regulation of oxidative phosphorylation

A
  • Normally oxidative phosphorylation and electron transport are tightly coupled - Both regulated by mitochondrial [ATP] - High ATP = low ADP - When [ADP] is low, no substrate for ATP synthase so inward flow of H+ stops - [H+] in intermitochondrial space increases, preventing further H+ pumping: stops electron transport - Reverses with low [ATP]
65
Q

Describe inhibition of oxidative phosphorylation

A
  • Inhibitors (prefers poisons as bind straight on) block electron transport e.g. cyanide prevents acceptance of electrons by terminal translocating oxygen - Pmf decreases, less energy for ATP synthesis -> ATP levels fall -> lethal
66
Q

Describe the uncoupling of oxidative phosphorylation

A
  • Uncouplers (e.g. DNP, fatty acids) increase permeability of membrane to H+ - H+ enters mitochondria without driving ATP synthase - Dissipates pmf - No phosphorylation of ADP - No inhibition of electron transport -> continues -> energy released as heat
67
Q

Describe the effect of oxidative phosphorylation diseases

A

Genetic defects in proteins coded by mitochondrial DNA (some subunits of PTCs and ATP synthase) lead to decrease in electron transport and ATP synthesis

68
Q

Describe the effect of oxidative phosphorylation coupling

A
  • NADH/O: 142kJmol^-1 lost. FADH2/O: 105kJmol^-1 lost - Rest of energy lost as heat - Efficiency depends on tightness of coupling - Can be varied in some tissues e.g. brown adipose tissues
69
Q

Describe brown adipose tissue

A
  • Contains thermogenin (UCP1): naturally occurring uncoupling protein - In response to cold, noradrenaline: 1. Activates lipase which releases fatty acids from triacylglycerol 2. Fatty acid oxidation -> NADH and FADH2 -> electron transport. Fatty acids activate UCP1 3. UCP1 transports H+ back into mitochondria so electron transport is uncoupled from ATP synthesis. Energy of pmf released as extra heat - Family of UCPs: role in heat generation by uncoupling but may have other functions
70
Q

Where is brown adipose tissue found?

A
  1. Newborn infants (higher proportion): to maintain heat, especially around vital organs. Small body and large surface area 2. Hibernating animals (metabolism turned down): to generate heat to maintain core body temperature
71
Q

Compare and contrast oxidative phosphorylation and substrate level phosphorylation

A

See image

My ESA1 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions