biochem exam 1 part II Flashcards

1
Q

glucose

A

the major fuel for most organisms

if totally oxidized, delta G = -2840 kJ/mol

versatile precursor: from it, can synthesize C=skseltons of most major molecules

fates in higher plants & animals:
- stored (polysaccharides, sucrose)
- oxidized to a 3-C compound (pyruvate): glycolysis
- oxidized to pentoses

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2
Q

fates of glucose

A

storage
- can be stored in polymeric form (starch, glycogen)
- when there’s plenty of excess energy
- glycogen, starch, sucrose

oxidation via glycolysis
- generates energy via the oxidation of glucose
- short-term energy needs
- pyruvate

oxidation via pentose phosphate pathway
- biosynthesis of lipids and nucleotides
- generates NADPH via oxidation of glucose
- ribose 5-phosphate

synthesis of structural polymerase
- cell walls of bacteria and plants
- ECM & cell wall of polysaccahrides

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3
Q

glycolysis

A

the almost-universal central pathway for carbohydrate catabolism (breakdown)

results in the storage of energy n atp and NADH

the first part of the catabolism of glucose, either anaerobic (fermentation - alcoholic or lactic acid) or aerobic

A 2-phase process

phase 1: preparatory (investment) phase
- glucose is phosphorylated and cleaved to form 1 molecule of glyceraldehyde3-phosphate. 2 ATP molecules are invested

phase 2- payoff phase
- 2 glyceraldehyde 3-phosphates are converted to 2 pyruvates. The payoff of 4 ATP and 2 NADH molecules

another representation:
energy investment phase:
2 ATP + glucose -> 2 ADP

energy payoff phase
4 ADP -> 4 ATP
2 NAD+ -> 2 NADH (reduction, step 6)

net:
glucose -> 2 pyruvate + 2 H2O
2ADP + 2Pi -> 2atp
2 NAD+ -> 2 NADH + 2H+

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4
Q

Fates of Pyruvate (More Later)

A

Aerobic Conditions: pyruvate is oxidized to yield the acetyl group of acetyl-coenzyme A.

That acetyl group is then oxidized completely to CO2 by the citric acid cycle

Pyruvate→Acetate→CO2 + H2O
NADH + O2 + 2H+ → NAD+ + H2O

Anaerobic Conditions:
Animals and microbes convert pyruvate into lactate when O2 is lacking

Through transforming pyruvate into lactate, NADH is oxidized to replenish NAD+

Replenishing NAD+ allows glycolysis (ATP production) to continue for a short time

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5
Q

Summary of Glycolysis and Energetics

A

how much of the energy in glucose is removed through glycolysis?

C6H12O6 (glucose) + 6O2 -> 6CO2 + 6H2O
delta G = -2840 kJ/mol

Glc + 2 NAD+ -> 2 pyruvate + 2 NADH + 2H+
delta G = -146 kJ/mol

146/2840 = 5.2%

much energy remains in pyruvate

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6
Q

Summary of Glycolysis and Energetics

A

glc + 2 NAD+ + 2 ADP + 2Pi
-> 2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O

glycolysis is very exergonic:
delta G = -85 kJ/mol

you can also think about glycolysis as a 2part process

Glc + 2 NAD+ ->. 2pyruvate + 2NADH + 2H+
delta G = -146 kJ/mol

2 ADP + 2Pi -> 2ATP + 2H2O
delta G = +61 kJ/mol

(-146 + 61 = -85 kJ/mol)

this shows that 146 kJ/mol are removed from glucose and 61 kJ/mol are stored as ATP

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7
Q

Summary of Glycolysis and Energetics

A

Glc + 2ATP + 2NAD+ 4ADP + 2Pi -> 2pyruvate + 2ADP + 2NADH + 2H+ +4ATP + 2H2O

or the net rxn:

Glc + 2NAD+ 2ADP + 2Pi -> 2 pyruvate + 2 ATP + 2 H2O

used:
1 glucose
2 ATP
2 NAD+

made:
2 pyruvate - various different fates
4 ATP - used for energy requiring processes within the cell
2 NADH - a high energy molecule, must be reoxidized to NAD+ in order for glycolysis

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8
Q

Glycolysis

A

1- 5: “preparatory phase”

Phase 1: - Preparatory (Investment) Phase Glucose is phosphorylated and cleaved to form 2 molecules of glyceraldehyde-3-phosphate. Two ATP molecules invested

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9
Q

Glycolysis: Step 1

A

Glucose-6-phosphate is produced
from blood glucose by hexokinase

Glucose phosphorylated at C-6

It keeps glucose in the cell!! because the phosphate is negatively charged and cannot pass through the phospholipid bilayer.

Glucose is now Charged - due to a negative charge from phosphate

Exergonic → irreversible
delta G = -16.7 kJ/mol

Uses/stores energy of ATP. First ATP invested! (other ATP investment is step 3 I think)

Hexokinase allosterically regulated by glucose-6-phosphate

Mg2+ lowers activation energy
(Ch #6 Biochem I – Enzyme Mechs)

1 - exergonic
2 - energy stored in the phosphate bond
3- regulated, steps 1,3,10
4 - induced fit

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10
Q

Glycolysis: Step 2

A

Isomerase converts glucose-6- phosphate to fructose-6- phosphate

6-membered ring to 5

Reversible (small ∆G) of 1.7 kJ/mol

Mg2+ lowers activation energy (Ch #6 Biochem I – Enzyme Mechs)

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11
Q

Glycolysis: Step 3

A

Fructose-6-phosphate is phosphorylated by phosphofructokinase-1 (PFK-1)

Fructose phosphorylated at C-1 Symmetrical☺now, 1,6-biphos.

Keeps all later products in the cell!! Charged.

Exergonic → irreversible Uses/stores energy of ATP

Second ATP invested!

Mg2+ lowers activation energy
(Ch #6 Biochem I – Enzyme Mechs)

1 - exergonic
2 - energy stored
3- regulated, steps 1,3,10
4 - induced fit

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12
Q

Glycolysis: Step 4

A

Fructose-1,6-bisphosphate is cleaved into two, 3-C molecules by aldolase:

  1. Glyceraldehyde-3-phosphate (G-3-P) ☺
  2. Dihydroxyacetone phosphate (DHAP)  Gotta change this!

1 -> 2 molecules: endergonic, but coupled to later rxns

  1. FROM HERE ON, EACH REACTION IS HAPPENING TWICE! (except Step 5 – ha!)
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13
Q

Glycolysis: Step 5

A

Dihydroxyacetone phosphate (DHAP) from Step 4 is converted to Glyceraldehyde-3-phosphate (G-3-P)☺ through triose phosphate isomerase

Now we have two G-3-Ps from 1 glucose!
Prep. Phase Done!

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14
Q

Glycolysis

A

6 - 10: payoff phase

Phase 2: - Payoff Phase
2 molecules of glyceraldehyde- 3-phosphate are converted to two molecules of pyruvate.

Four ATP molecules and 2 NADH molecules were produced.

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15
Q

Glycolysis: Step 6

A

Glyceraldehyde 3-phosphate is phosphorylated/oxidized to 1,3-bisphosphoglycerate

NAD+ is reduced to NADH

1,3-Bisphosphoglycerate has a phosphate group we can cleave, and release energy to drive reactions (remember reaction coupling?). Also storing energy in the NADH.

G3P is oxidized and NAD+ is reduced (a redox rxn!!!)

NAD+ is reduced to NADH

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16
Q

Glycolysis: Step 7

A

ATP is synthesized (2 ATPs come back→net = zero at this point) as phosphoglycerate kinase transfers the phosphate group from 1,3-Bisphosphoglycerate to ADP

1,3-Bisphosphoglycerate → 3-Phosphoglycerate + ATP

Energy released used to pull previous rxns 4, 5 & 6

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17
Q

Glycolysis: Step 8

A

3-Phosphoglycerate → 2-Phosphoglycerate Just moving a phosphate group around

isomerization, small delta G

18
Q

Glycolysis: Step 9

A

2-Phosphoglycerate doesn’t have a lot of energy compared to other compounds:
Phosphoenolpyruvate

So let’s convert 2-phosphoglycerate to Phosphoenolpyruvate (PEP) via enolase

Dehydration has a small deltaG

19
Q

Glycolysis: Step 10

A

Phosphoenolpyruvate →Pyruvate + ATP

Via pyruvate kinase

Here is where we gain 2 ATP and now net two ATP.

THIS IS THE PAYOFF!

Irreversible

Note the Mg2+

Vry exergonic hydrolysis of PEP coupled to ATP formation stores energy and drives the whole process; allosterically regulated

allosterically Activated by: AMP and fructose-1,6-biphosphate

Allosterically Inhibited by: ATP and acetyl-CoA

20
Q

summary of glycolysis and energetics

A

Glc + 2 ATP + 2 NAD+ 4 ADP + 2 Pi
–> 2 Pyruvate + 2 ADP + 2 NADH + 2 H+ 4 ATP + 2 H2O

or the net rxn:

*Glc + 2 NAD+ 2 ADP + 2 Pi
—> 2 pyruvate + 2 NADH + 2 H+ 2 ATP + 2 H2O

used:
1 glucose
2 atp
2 nad+

made:
2 pyruvate - various different fates
4 ATP - used ro energy-requiring processes within the cell
2 NADH - a high energy molecule, must be reoxidized to NAD+ for glycolysis to continue

21
Q

Which of the steps of glycolysis is/are regulated?

A
1, 3

B
1, 3, 7, 10

C
1, 3, 10

D
7, 10

A

C
1, 3, 10

7 & 10 have ATP coming out

1 & 3 have ATP going in

22
Q

Glycolysis and Cancer

A

in most tumors, there is limited O2 availability ( hypoxia) and therefore less aerobic metabolism

for ATP production, cells become more dependent on glycolysis. Glucose uptake increases and glycolysis is accelerated

one type of chemotherapy targets glycolysis

so since there is not a lot of O2, the tumor uses glycolysis to get its energy

23
Q

Other Pathways Can Lead to the Glycolysis Pathway

A

Multiple feeder pathways exist for glycolysis:
- Glucose cleaved from glycogen and starch (polysaccharides) to give glucose-1- phosphate
- Dietary disaccharides and polysaccharides are hydrolyzed

getting sugars to feed into glycolysis

KNOW: that not all sugars are glucose and need to have different pathways to get different sugars to enter into glycolysis

24
Q

Polysaccharide Feed-in to Glycolysis

A

how glycogen enters glycolysis

non-reducing ends at the glycogen units

glycogen phosphorylase cuts off the non-reducing ends into glucose 1 phosphate

then made into glucose 1 phos.

glucose 1 phos. + isomerse = G6P and can enter into glycolysis

starch + amylase in mouth
= maltose + dextrins to make glucose

glucose + hexokinase = G6P and can enter glycolysis

25
Q

Disaccharide Feed-in to Glycolysis

A

maltose + maltase = 2 glucose

*lactose + lactase = glucose + galactose

sucrose + sucrase = glucose + fructose*

trehalose + trehalase = 2 glucose

26
Q

Monosaccharide Feed-in to Glycolysis

A

in liver:
fructose –> glyceraldehyde 3 phos.

muscle & kidney
fructose –> fructose 6 phos.

mannose –> fructose 6 phos.

primarily in the liver
galactose –> G1P –> G6P

27
Q

Fates of Pyruvate

A

Aerobic Conditions: pyruvate is oxidized to yield the acetyl group of acetyl-coenzyme A.

That acetyl group is then oxidized completely to CO2 by the citric acid cycle

Pyruvate→Acetate→CO2 + H2O
NADH + O2 + 2H+ → NAD+ + H2O

Anaerobic Conditions:
Animals and microbes convert pyruvate into lactate when O2 is lacking

Through transforming pyruvate into lactate, NADH is oxidized to replenish NAD+

Replenishing NAD+ allows glycolysis (ATP production) to continue for a short time

28
Q

anaerobic metabolism: pyruvate to lactate in human muscle cells

A

pyruvate + lactate dehydrogenase + NADH + H+ –> NAD+ + Lactate

during vigorous exercise, lactate accumulate in muscle tissue, eventually causing pain and possibly limiting exercise capability

29
Q

anaerobic metabolism: pyruvate to ethanol in yeast

A

in yeast and some other organisms

thiamine pyrophosphate (TPP) a coenzyme derived from thiamine is often required for decarboxylation rxns when the carboxyl group is adjacent to carbonyl group

pyruvate —> acetaldehyde —> ethanol + CO2 + NADH to NAD

29
Q

Under anaerobic conditions in human muscle cells, pyruvate is metabolized to…

A
Acetyl-CoA

B
Ethanol

C
Lactate

D
PEP

E
TPP

A

C
Lactate

IN YEAST it is ethanol

30
Q

from catabolism (breakdown) to anabolism (synthesis)

A

we just did catabolism

now we will go over anabolism

glycolysis (catabolism) is related to gluconeogenesis (anabolism)

catabolism:
- we have 3 carb. molecules
- make ATP, NAD(P)H, precursors

anabolism
- use ATP, NAD(P)H, precursors to make carbs and various other molecules

31
Q

Carbohydrate Biosynthesis

A

anabolism going on

plants
- CO2 + light = starch and sucrose photosynthesis

animals
- take catabolic products (pyruvate, lactate) and make them into anabolic products

32
Q

organizing principles of biosynthesis

A
  1. antiparallel pathways: may share some reversible rxns with catabolic pathways, but there is usually 1 irreversible unique to each way - at steps 1, 3, 10
  2. regulation: at least 1 - coordinate reciprocal - usually early in the chain
  3. rxns usually coupled to ATP hydrolysis (exergonic) to make the process irreversible
33
Q

Our Body Needs Glucose…all the time, constantly,…

A

the brain, nervous system, erythrocytes, testes, renal medulla, and embryo tissues, are completely or majorly dependent upon glucose for fue

the body carriers only a little more than a 1 day’s supply of glucose

what if glucose stores run out

if glucose is not obtained in the diet, the body must produce new glucose from noncarbohydrate precursors

34
Q

central pathway from precursor to carbohydrates: gluconeogenesis the system for glucose

A

anabolic

occurs in almost all organisms

in animals, for the cells of many organs (especially the brain) glucose is the major or sole energy source

in higher animals, primarily in the liver

main precurosrs: pyruvate , lactate

and/or: oxaloacetate, glucogenic amino acids

glycolysis:
- start with glucose
- end with pyruvate

gluconeogenesis
- start with pyruvate
- end with glucose

35
Q

Glycolysis and Gluconeogenesis

A

7 common enzymes

3 rxns of glycolysis are so exergonic that they are irreversible:
- step 1: hexokinase
- step 3: phosphofructokinase-1 (PFK-1)
- step 10: pyruvate kinase

gluconeogenesis ‘detours’ around these

Gluconeogenesis is not the reverse of glycolysis

The three exergonic and highly regulated reactions in glycolysis are
replaced by alternative reactions in the gluconeogenic pathway.

The results of these reactions are similar intermediates

36
Q

glycolysis and gluconeogenesis

A

7 & 10 rxns are shared

bypasses for the 3 very exergonic (~irreversible) rxns

37
Q

Gluconeogenesis Step 1: (Bypass of Glycolysis Step 10)

A

Antiparallel to Glycolysis Step 10.

  • Glycolysis: PEP → Pyruvate
  • Gluconeo. Pyruvate→oxaloacetate→PEP
  • Complex and costly (1 ATP + 1 GTP), need to put energy into bonds to build something new
  • Exergonic(because of the above)
  • NADH consumed in mitochondria, reformed in the cytosol
  • What do you think stimulates/inhibits these enzymes?
    Consider what we are doing…

glucose to pyruvate and o2 was around so we went to the citric acid cycle

38
Q

Gluconeogenesis Step 1: (Bypass of Glycolysis Step 10)

A

biotin: cofactor involved in CO2 transfer

CO2 + pyruvate –> oxaolocateose + phosphate

costs energy, uses GTP

biocarbonate + pyruvate …

39
Q

when pyruvate is available

A

bypass #1a: a complex process

oxaloacetate cannot go through mitochondria so it needs to be turned into malate then converted back into PEP

pyruvate from cytosol goes into mitochondria
pyruvate turns into OA
OA to malate
malate in mitochondria goes to the cytosol
malate to OA
OA to PEP

40
Q

Bypass #1 rxns

A

summary:

pyruvate to OA
OA to malate
malate to PEP

not finished yet…

also when lactate is available (usually inn muscle cells) then it can turn into pyruvate, which can turn into OA, malate, back to OA then to PEP

Also NADPH determines the fate of G6P whether it goes to PPP to make amino acids and nucleotides or glycolysis to be broken down into pyruvate for storage for when we need to make more glucose