METABOLISM SYLLABUS 2: Glycolysis: functions, pathway, energetics, regulation Flashcards Preview

MCG > METABOLISM SYLLABUS 2: Glycolysis: functions, pathway, energetics, regulation > Flashcards

Flashcards in METABOLISM SYLLABUS 2: Glycolysis: functions, pathway, energetics, regulation Deck (40):
1

function of glycolysis?

1) provide energy for cells 

2) provide intermediates for other metabolic reactions - like a-glycerophosphate for triglyceride and phoshpolipid synthesis; 2,3 bis-phophoglycerate in RBC; acetyl CoA from pyruvate; amino acids such as serine, alanine, glycine 

2

how do RBC get energy?

ONLY via glycolysis

3

to what organs is glycolysis the major source of energy (not the only)?

embryonic tissue, retina, adrenals, immune cells, exercising muscle 

4

name the steps of glycolysis 

* denotes irreversible step * 

*1: GLUCOSE to G6P via hexokinase

2: G6P to F6P via phosphoglucose isomerase 

*3: F6P to F1,6BP via PFK-1

4: F1,6BP to DAP + G3P via aldolase

5: DHAP to G3P via isomerase

(everything hereforeward is x2)

5: G3P to 1,3BPG + NADH via G3PDH 

6: G3P to 1,3BPG via G3PDH

7: 1,3BPG to 3PG via PG kinase

8: 3PG to 2PG via PG mutase 

9: 2PG to PEP via enolase 

*10: PEP to Pyruvate via Pyruvate Kinase 

5

what are hexokinases

constituitive enzymes w/ a low Km for glucose 

subject to product inhibition by G6P and ADP 

not specific for glucose

6

what is glucokinase? 

what are its unique properties?

the hexokinase isoform in the liver and pancreas 

- has a high Km for glucose, is specific for glucose

- is not subject to inhibition by G6P and ADP, so will keep working when these products are produced

- its levels are increased at transcriptional level by high carb diet and insulin

- is repressed at transcription level by glucagon/epi

- increases mRNA levels 

7

why is glucokinase > hexokinase for liver function?

because glucokinase has a high Km for glucose, so it only works when glucose levels are high, i.e. after meals 

thus liver only will respond to high glucose levels 

8

what kind of reaction is the phosphoglucoisomerase (step 2) reaction?

G6P -> F6P is acid:bases catalysis by an enzyme

9

what is the rate limiting step of glycolysis?

step 3, by PFK; it is irreversible 

involves input of ATP 

F6P + ATP -> F1,6 bis P + ADP 

 

10

what inhibits/stimulates PFK?

INHIBITORS: ATP, citrate, glucagon

ACTIVATORS: AMP, Pi, NH4+ , F1,6 bis P, insulin

 

11

is PF-1-K highly regulated?

yes, because it's the rate-limiting step of glycolysis

12

what is F2,6 bis P ? how is it synthesized/broken down?

powerful activator of PFK 

produced from F6P + ATP -> ADP + F2,6bisP -> F6P + Pi

it is created by action of F2,6 bis phosphokinase 

it is broken down by F2,6 bis phosphofructophosphatase to F6P + Pi

13

what is the active/inactive state of the F2,6 bis P kinase/phosphatase?

what is its effect on PFK?

what controls these states?

when F 2,6 bis P kinase is dephoshporylated it is active; when it is phosphorylated and inactive 

when F 2,6 bis P phosphatase is dephoshporylated it is inactive; when it is phosphorylated and active 

 

thus PFK is active when F2,6 bis P kinase is dephosphorylated, thus ALLOWING STEP 3 of glycolysis to proceed

 

this is controlled by insulin, glucagon/epi:

INSULIN promotes the DEPHOSPHORYLATED, ACTIVE state of the kinase, F 2,6 bis P

GLUCAGON/EPI promote the PHOSPHORYLATED, INACTIVE state of the kinase

14

what are the outcomes of the ALDOLASE reaction?

F 1,6 Bis P -> G3P + DHAP 

1) DHAP can -> alpha glycero P, which is needed for triglyceride and phospholipid synthesis 

2) or DHAP is converted to G3P by triose phosphate isomerase to continue glycolysis 

 

15

what is the G3PDH rxn?

what inhibits the G3PDH reaction? why?

STEP 6 of glycolysis

thiol-reacting compounds and heavy metals such as lead, mercury, cadmium 

they thus inhibit glycolysis 

b/c G3PDH has thiol groups necessary for its activity, it is reactive w/ these compounds

16

what is the first ATP-producing step of glycolysis?

STEP 7: phosphoglycerate kinase reaction

produces 2 ATPs (1 for each G3P made from the 1 glucose undergoing glycolysis)

1,3 bis PGA + ADP 3 PGA + ATP 

occurs b/c 1,3 bis PGA is a high-energy compound 

 

17

what is substrate level phosphorylation? when in glycolysis does it occur? 

production of energy in the form of ATP without mito or oxygen 

occurs when 1,3 bis PGA + ADP -> 3PGA + ATP 

 

 

18

what does 1,3 bis PGA do for energy of the glycolysis rxn?

it traps energy, allows its release as ATP 

if not for 1,3 bis PGA, this energy would ahve been released as heat: 

G3P + NAD+ 3PGA + NADH + heat 

instead of: 

G3P + Pi + NAD+ NADH + 1,3 bis PGA [add ADP]  3PGA + ATP

19

why is arsenic toxic?

it competes w/ Pi for G3P, forming 1-arseno-3-phophoglyceric acid which is not a high energy compound like 1,3 bis PGA 

this immediately decays to 3PGA + heat, w/o ATP production 

20

what does the RBC mutase do?

moves Pi, converts small amounts of 1,3 bis PGA to 2,3 bis PGA 

this is an important allosteric effector of hemoglobin:oxygen affinity

21

what in glycolysis can produce serine?

3PGA

22

what is fluoride's effect on glycolysis?

inhibits enolase, STEP 9 

this blocks glycolysis 

23

what is yielded from the final step of glycolysis?

pyruvate kinase catalyzes the high energy PEP to yield 2 ATP

IRREVERSIBLE REACTION

24

how many ATP are produced from each glucose -> 2 pyruates of glycolysis?

2 ATP used at the beginning in hexokinase, PFK steps 

4 ATPs produced, 2 at G3P and 2 at pyruvate kinase step

NET: 2 ATP 

25

what inhibits or activates pyruvate kinase activity?

INHIBITORS: ATP, NADH, acetyl CoA: indicate high energy 

 

STIMULATORS: F1,6 BIS P, the PFK reaction's product

INSULIN stimulates 

 

 

26

is pyruvate kinase active or inactive when phoshporylated? what causes phosphorylated or dephosphorylated state?

PK is INACTIVE when PHOSPHORYLATED, via GLUCAGON -> CAMP-PKA PHOSPHORYLATION

 

PK is ACTIVE when DEPHOSPHORYLATED, via INSULIN

27

how does K+ regulate Pyruvate Kinase activity?

PK needs high intracellular levels of K+ for its activity 

this is mediated by the Na+/K+ ATPase 

 

28

what amino acid can pyruvate produce? 

alanine

29

3 irreversible steps of glycolysis?

hexokinase, PFK, PK reactions

30

how does insulin regulate glycolysis

STIMULATES it by:

1) INCREASING GLUCOKINASE LEVELS

2) ACTIVATING the PFK and PK reactions via DEPHOSPHRYLATIONS 

31

how does glucagon regulate glycolysis

INHIBITS it by 

1) DECREASING GLUCOKINASE levels 

2) INHIBITING PFK and PK via cAMP-PKA-dependent PHOSHPORYLATIONS

32

what high energy signals impact PK activity?

INHIBIT it 

ATP, citrate 

33

what inhibits PK

high energy signals like ATP, NADH, acetyl CoA

34

how does fructose interact w/ glycolysis?

LIVER acts on F1P via liver aldolase B, producing DHAP + glyceraldehyde

DHAP enters glycolysis 

glyceraldehyde is phoshporylated to G3P by triosephosphokinase, enters glycolysis 

thus DHAP and G3P from F1P can enter glycolysis and become pyruvate or go opposite way and become glucose 

35

what are liver aldolase B's actions?

1) can cleave F1P in the liver

2) can leave F1,6 bis P in other tissues, thus contribute to glycolysis

36

what is the cause of hereditary fructose intolerance? what happens?

aldolast B deficiency 

these individuals cannot metabolize F1P 

F1P accumulates in the liver; a high level of accumulation depletes ATP and is toxic to the liver 

37

how do you treat hereditary fructose intolerance?

limit fructose and sucrose in the diet

38

what causes lactose intolerance?

deficiency in lactase, the enzyme that hydrolyzes lactose into glucose and galactose 

39

what occurs in galactosemia?

deficiency of galactose-1-phosphate uridylyltransferase 

thus cannot convert Galactose-1-P -> Glucose-1-P

Galactose-1-P accumulates, and this is toxic to the liver

 

treat by: eliminating lactose from diet, which comes from lactose 

this is a problem for nursing mothers! 

40

do tumors have rapid or slow rate of glycolysis?

rapid 

because glycolysis is a rapid way to produce ATP in absence of oxygen and mitochondria which often are poorly coupled or functional in tumors

Decks in MCG Class (77):