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Catabolism of Carbohydrates Flashcards

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0
Q

Where does glycolysis occur?

A

In cell cytoplasm

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1
Q

Where is the major site for fructose and galactose metabolism?

A

L-L-L-L-LIVER!

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2
Q

Describe the redox reaction that occurs in glycolysis?

A

Glucose is oxidised to pyruvate.

NAD+ is reduced to NADH

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3
Q

How many enzyme controlled steps are in glycolysis?

A

10

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4
Q

Which of the steps in glycolysis are irreversible?

A

1,3&10

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5
Q

In Which tissues does glycolysis occur?

A

All are active

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6
Q

What is the function of glycolysis?

A
  • produce ATP
  • produce NADH from NAD+
  • produce building blocks for anabolism
  • useful intermediates for specific cell function
  • starting,ending and intermediate products either C3 or C6
  • no loss of CO2
  • redox of oxidising glucose to pyruvate and reducing NAD+ to NADH
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7
Q

Is glycolysis exergonic or endogonic?

A

Exergonic. Gibbs is -ve delta G.
Intermediates phosphorylated, some with high energy phosphoryl group
2 moles of ATP invested to activate process, to make glucose unstable.
4 moles of ATP produced.
Net gain of 2 moles

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8
Q

Step 1 of glycolysis is catalysed by…?

A

Hexokinase
Phosphate + glucose —> Glucose -6-phosphate
(ATP–>ADP)

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9
Q

Step 3 of glycolysis is catalysed by…?

A

Phosphofructokinase
Fructose-6-Phospate –> Fructose-1,6-bisphosphate
Using ATP

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10
Q

Step 10 of glycolysis is catalysed by…?

A

Pyruvate Kinase.
PEP—> Pyruvate
Removal of phosphate (ADP+Pi—>ATP)

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11
Q

ATP synthesis in Glycolysis is called?

A

Substrate-level phosphorylation

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12
Q

When the food consumed is broken down to Carbs, lipids and proteins which bonds are broken?

A

C-N & C-O

No energy produced.

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13
Q

When carbs, lipids and proteins are taken into the intracellular what occurs?

A

Building blocks hydrolysed into simple molecules.
Oxidation requiring Co-factors
C-C BONDS BROKEN
Some ATP produced

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14
Q

What is the rate of cellular glucose uptake dependant on?

A

The blood conc of glucose

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15
Q

What is the minimum requirement of glucose for a healthy adult?

A

180g/day

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16
Q

What tissues depend on glucose?

A

RBC, WBC, kidney medulla, lens of eyes and CNS heavily depends on glucose.

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17
Q

Phosphorylation of glucose by hexokinase is important because?

A
  • increased reactivity of glucose
  • sugar becomes anionic (-ve) hence does not pass plasma membrane
  • formation of high phsophyl group transfer potential, hence Pi + ADP –> ATP
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18
Q

Talk about a lack of fructokinase:

A

Frutokinase catalyses the phosphorylation of fructose to Fructose-1-P, hence a deficiency in the enzyme leads to fructose present in the urine but no other clinical signs.

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19
Q

Talk about he lack of aldose in fructose metabolism:

A

Deficiency of aldose is severe.
Aldose catalyses the conversion of Fructose-1-P to G-3-P, hence deficiency results in build up of F-1-P hence liver (site of fructose metabolism) damage occurs.
Tx = remove fructose from diet.

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20
Q

What is phosphofructokinase inhibited by?

A

High ATP:ADP ratio in the muscle

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21
Q

What is phosphofructokinase activated by?

A

In the liver, high insulin:glucagon

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22
Q

Which step of glycolysis is the committing step?

A

Step 3

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23
Q

What enzyme catalyses the reversible reaction between DHAP and G-3-P?

A

G-3-P dehydrogenase

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24
What is DHAP used for?
Used in the liver and adipose tissue. | Biosynthesis of TAGs and Phospholipid bilayelipid synthesis in the liver requires glycolysis.
25
What is the chemical equation of glycolysis?
Glucose + 2ADP + 2Pi + 2NAD+ --> | 2Pyruvate + 2ATP + 2NADH + 2H2O + 2H+
26
What is hexokinase inhibited by?
High G-6-P
27
In anaerobic respiration, what happens to pyruvate?
Pyruvate is reduced to lactate by LACTATE DEHYDROGENASE. This therefore deoxidises NADH to NAD+ hence can continue to oxidise glucose in glycolysis to produce some substrate level ATP
28
What occurs with slightly too much lactate?
Hyperlactaemia | Hence no change to blood pH and the level is below renal threshold
29
What occurs with extremely high lactate?
``` Lactate Acidosis Lactate above 5mM hence above renal threshold. Lactate excreted Blood pH falls. Can cause coma. ```
30
Why is it efficient to have multiple steps in Glycolysis?
- efficient energy conversion | - versatility as interconnections to other pathways, useful intermediates and so reversible steps, also control.
31
How is glycolysis used in the diagnosis of cancer?
Rate of glycolysis is 200x faster | Using PET imaging
32
What is allosteric regulation?
Enzymes are activated/inhibited by the binding of molecules to their - catalysis sites hence converts the sub. to prod. - regulatory sites
33
What enzymes in Glycolysis are allosterically regulated?
Hexokinase Phosphofructokinase Pyruvate Kinase
34
What is covalent modification of enzymes?
A regulatory mechanism whereby enzymes may be phosphorylated or dephosphorylated. The transfer of a -ve charged phosphate from ATP to an amino acid residue.
35
Which cells/tissues produce lactate?
RBC, skeletal muscle, GI & brain
36
Where is lactate metabolised?
Heart and liver
37
Why is 1,3-BPG important?
Using BISPHOSPHATE MUTASE, in RBCs it is converted to 2,3-BPG which is used in regulating O2 affinity of Hb.
38
Flow of glycolysis is determined by which types of steps?
The rate determining steps, esp. Step 3
39
What happens to lactate in the heart?
Lactate --> Pyruvate --> CO2
40
What happens to lactate in the liver and kidneys?
Lactate --> Pyruvate --> Glucose
41
Why are lactate blood levels stable?
Rate of production = utilisation | So plasma levels constant <1mmol/L
42
When might there be high lactate levels?
``` High production: - Strenuous Excercise - Shock - Congestive Heart Disease Low utilisation: - liver disease - thiamine deficiency (lack of NAD+) - alcohol metabolism ```
43
Where is galactose mainly metabolised?
The liver | Some in GI and kidney
44
What enzymes are involved in metabolism of Galactose?
Galactokinase using ATP Galactose-1-phosphate uridyl transferase (Epimerase)
45
What is GALACTOSAEMIA?
Lack of kinase or transferase enzyme. Kinase is rare, and is accumulation of galactose in tissue. Transferase is more common and serious, as galactose and Galactose-1-P accumulate hence reduced to GALACTITOL by ALDOSE REDUCTATASE
46
Why is GALACTITOL bad?
Conversion of Galactose to GALACTITOL depletes NADPH levels hence disulphide bridges form in the lens of eyes = cataracts. Also, no glycosylation of lens because of high galactose levels. If untreated, high galactose and galactitol levels lead to glaucoma --> blindness
47
Why is accumulation of Galactose-1-phosphate bad?
Damage to liverm kidney and brain.
48
At what stage does the Pentose Phosphate Pathway occur?
Glucose-6-Phosphate
49
Where does PPP occur?
Liver, RBC and Adipose.
50
Function of PPP:
``` Produce NADPH in cytoplasm -biosynthesis by reducing power eg lipid synthesis -highly active in adipose Maintain free -SH on certain proteins - prevents oxidation, hence formation of -S-S- Produces Pentose sugars for nucleotides -highly active in bone marrow ```
51
What is G-6-P dehydrogenase deficiency?
Very common, inherited. Lack of the enzyme that converts G-6-P into 5C sugar phosphates. Hence in RBC, lack of NADPH leads to Heinz Bodies and HAEMOLYSIS
52
Characteristics of PPP?
-no ATP production -loss of CO2 -irreversible -controlled by NADPH/NADP+ ratio. hence inhibited by high NADPH levels
53
What enzyme catalyse the conversion of Pyruvate to Acetyl CoA?
Pyruvate Dehydrogenase
54
Why is the the conversion of Pyruvate to Acetyl CoA irreversible?
Loss of CO2
55
What Co-factors are involved in the conversion of Pyruvate to Acetyl CoA?
FAD Thiamine Pyrophosphate Lipoid Acid
56
What type of Vitamin deficiency is the conversion of Pyruvate to Acetyl CoA sensitive to?
Vitamin B
57
What activates Pyruvate dehydrogenase?
``` Pyruvate NAD+ CoA ADP Insulin ```
58
What inhibits Pyruvate dehydrogenase?
Acetyl CoA NADH ATP
59
Where is Acetly CoA found?
Mitochondrial Matrix
60
What is the anabolic functions of the TCA cycle
- C5 and C4 intermediates used for synthsis of nom-essential AAs - C4 to heam and glucose - C6 to FAs
61
What is GTP?
Practically ATP
62
What enzyme is important for TCA cycle?
Isocitrate dehydrogenase | Activated by NAD+, inhibited by NADH
63
In starvation, how is glucose levels maintained?
Amino acids hydrolyse to oxaloacetate, which is converted into glucose. This is gluconeogenisis.
64
What are the convoluted inner mitochondrial membranes called?
Cristae | Increasing SA
65
What is the Proton Motive Force?
The NADH and FAD2H becomes reoxidised at the elctron transport chain, it deposits its electrons in the complexes which results in the pumping of protons across the inner membrane due to the elctron free energy. As the inner memebrane is impermeable, and no anions transfer across, there is a proton gradient produced across the memebrane. This produces a p.m.f which turns the ATP synthase to converts ADP + Pi --> ATP via chemiosmosis and generating energy via Oxidative Phosphorylation.
66
How much total ATP is produced?
32 moles
67
What regulation occurs at the ETC?
When high ATP, or low protons in intermembrane space. ATP synthase stops and prevents protons moving into inter memebrane space. Protons are still pumped across at the ETC, hence increasing conc. Absence of protons in matrix stops the pumping across the ETC.
68
How is energy lost as heat in the ETC?
P.m.f. Coupled to ATP synthase hence, if the coupling is not as tight then energy lost as heat.
69
What are the three complexes called?
Proton Translocating Carriers
70
Why is oxygen important for the ETC?
It is the terminal electron acceptor. It allows the complexes to carry the chemical bond energy of electrons to Translocating the protons across the membrane.
71
What determines the amount of ATP produced?
The extent of P.M.F. | The greater the P.M.F, the more ATP produced.
72
How much ATP is produced form 2 moles of NADH? 2 moles of FAD2H
2. 5 moles | 1. 5 moles
73
Name some examples of uncouplers?
Dinitrophenol | Dinitrocresol
74
What does uncouples do and why is it important?
Increase the permeability of the inner memebrane hence protons re-enter the matrix without driving the ATP synthase (uncoupled) hence energy is dissipated as heat. This is important to account for 20% of BMR.
75
What are UCPs?
Uncoupling proteins, UCP1-5, 1-3 most important. | They uncouple the ETC with ATP production, hence produce heat.
76
What is UCP-1?
Thermogenin. Expressed in brown adipose tissue, enabling animals to survive in cold environments by non-shivering thermogenesis. Noradrenaline for SNS --> lipolysis ---> FA release ---> beta-oxidation for brown adipose tissue Noradrenaline---> activates UCP-1 hence dissipation of p.m.f as heat.
77
What about UCP-2?
Found in the whole body, could be linked to diabetes, obesity, metabolic syndrome and heart failure.
78
What about UCP-3?
Found in skeletal muscle, brown adipose and the heart. Modifying FA metabolism, protecting again reactive oxygen species. UCPs important pharmacologically.
79
ETC inhibitors?
Inhibited under anaerobic respiration. Substances: CO, poisons (cyanide, antimycin) prevent proton translocation, not p.m.f, no ATP production. Death. Cyanide destroys the 3rd Carrier
80
Differences in enzymes between OP & SLP?
OP - membrane associated complexes in inner mit membrane SLP- soluble enzymes in cytoplasm and mit. Matrix
81
Differences in energy coupling between OP & SLP?
OP- occurs indirectly from generation and utilisation of the p.m.f. SLP- directly from formation of high energy of hydrolysis bonds (phosphate transfer)
82
Differences in oxygen between OP & SLP?
OP can not occur without oxygen SLP can occur to a limited extent
83
Differences in overall ATP synthesis between OP & SLP?
OP is the major process in cells requiring large amounts SLP is the minor process in cells requiring little amounts
84
Why is step 3 the committing step?
It's large negative delta G value

Metabolism (8 decks)

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