3. CH 14 Glycolysis

8/8/2019 3. CH 14 Glycolysis

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Glycolysis, Gluconeogenesis, and thePentose Phosphate Pathway

Chapter 14

LehningerPrinciples of Biochemistry

5th edition

By Nelson & Cox



1. Good fuel ( ___ standard free energy).

2. Storage: starch or glycogen

(high MW polymers): - does not affect cytosolic _________

could be used in future when energydemand increases.

3. Oxidation via __________________________

Glucose

1

2

3

Major fates in animals and vascular plants:

•Central place in metabolism



Oxidation of glucose

C6H

12O

6 + 6O

2 6CO

2 + 6H

2O

Glycolysis

•During this reaction some of the free energyis conserved as _____ or _______.

Fermentation: Anaerobic breakdown of glucose andothers to obtain energy as ATP.

Most ______ form of energy obtaining process?



Glycolysis

-Breakdown of 6-C glucose into-two molecule of the 3-C __________

-occurs in 10 steps.

- First five (1-5) are ________ phase- energy investment

- Last five (6-10) are ________ phase

aerobic



Hexokinase – ATP & Mg2+ - ______ reversible (under intracellular condition).

- Hexokinase kinase transfers terminal phosphoryl group from _____ to an acceptor.

- Hexokinase is present in ______ of all organisms.

p532

1. Phosphorylation of Glucose

negative charged sugar: cannot _____ the cell.

Preparatory Phase of Glycolysis



Phosphohexose isomerase – Mg2+

- Isomerization reaction - Freely __________ If slight ______ in product, reverses reaction.

2. Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate




Phosphofructokinase 1 (PFK-1) – ATP & Mg++

– Essentially ___________ / first __________ step

• Fructose 1,6-bisphosphate is targeted forglycolysis.

- It is a major point of _________ in glycolysis.- ATP & PEP __________ regulate PFK1

3. Phosphorylation of Fructose 6-P to Fructose 1,6-bisphosphate

p526

Fructose 6-phosphate

G´°

= –14.2 kJ/mol




4. Cleavage of Fructose 1,6-bisphosphate

AldolaseFreely _________ : yields two ________ trioses

- Lower concentration of reactants for reverse reaction.

(Products are _____________up by subsequent reaction) p533




5. Interconversion of Triose Phosphates

Triose phosphate isomerase- Only G3-P (Glyceraldehyde 3-phosphate) can be ________

degraded.

- Dihydroxyacetone phosphate is readily converted into

_______ .

- Freely __________ reaction but moves in forward direction

because product is readily used up.




Glyceraldehyde 3-phosphate dehydrogenase - Ist step in payoff phase (energy conserving) leading to

ATP formation later on.

- Freely ________

- Acceptor of hydrogen is ________ yielding NADH.

6. Oxidation of G3-P to 1,3-Bisphosphoglycerate

p535

G’̊ = 6.3 kJ/mol

Payoff Phase of Glycolysis



Phosphoglycerate kinase – Mg2+• ___________ level phosphorylation.

(different from respiration-linked synthesis of ATP)• Freely reversible, but highly _______________

7. Phosphoryl transfer from 1,3-Bisphosphoglycerate to ADP

p536




Phosphoglycerate mutase – Mg2+

- Freely reversible

- Shifts phosphoryl group between C-3 and C-2

8. Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate




Enolase (dehydratase) - Freely reversible,

- Removes _____ from 2-Phosphoglycerate to yield ___.-

9. Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate

Sets up ____ substrate-level phosphorylation


PEP



Pyruvate kinase (PK) – ADP & Mg2+

Yield is ________ per glucose molecule.(substrate-level phosphorylation)

PK is ____ reversible

10. Transfer of phosphoryl group from PEP to ADP

Pyruvatekinase

Mg 2+ , K+

p538




Products of Glycolysis?

• ________

• ________ • ________



What happens to these three products?

– ATP is ________ source.– NADH makes more ATP if Oxygen is

_________.

– Pyruvate is further _____ if Oxygen isavailable

- contains majority of the energy.

–

Anaerobic conditions produce _______ result.



Other carbohydrates:

1.Storage polysaccharides: ____________ & __________.

2. disaccharides: _________, ______, _______ & ________.

3. monosaccharides:

__________, mannose, galactose



Feeder pathways for Glycolysis

The trick is to make:

Glycolytic _______________

may involve one or more specific _______.



Feeder pathways for Glycolysis



1. Catabolism of Polysaccharides

•Digestive tract or sprouting seeds- hydrolyzed by __________

- maltose & glucose released

•Intracellular- transfer of glucose to Piby

___________

- glucose 1-phosphate released

Starch (______), and Glycogen (______) can be used

in the same _________.

Dietary glycogen/starch (similar structure) is brokenby hydrolysis through use of _________ not Pi.

http://en.wikipedia.org/wiki/File:Amylose2.svg

t ll l

http://en.wikipedia.org/wiki/File:Amylose2.svg



Glycogen and Starch

Two enzymes needed

1. Glycogen Phosphorylase :catalyzes an attack by Pi onthe ____________ bond that joins last two glucose

residues at the _____________ end.

- glucose 1-phosphate

This enzyme works until itreaches a glucose that is within _____residues of an:

_______ branch point.(glycogen & amylopectin).

tracellular



• Debranching enzyme has 2 activities– Transferase – moves

______ glucose unitsfrom the _____ branch

to the ______ branch

– Glucosidase – releases afree _______ byhydrolyzing the

-1,6-glycosidic bond

Glycogen and StarchDebranching



Glycogen and Starch Detail

2. Phosphoglucomutase

- Converts Glucose 1-phosphateto Glucose ___-phosphate

Glucose 1-phosphate

Glucose ___-phosphate

- Freely ________ reaction

GlycogenPhosphorylase



Hydrolysis of dietary polysaccharide: (breakdown of starch)

•Salivary -amylase: smaller _______________(digestion begins in mouth).

•Pancreatic -amylase : maltose & maltotriose

(di- and trisaccharides of glucose) and dextrins.

•Maltose and dextrins are further degraded byenzymes

into ___________.

•Disaccharides must be hydrolyzed to ____saccharides

before entering cells.



2. Catabolism of Disaccharides

•Maltose – from breakdown of starches Maltase – 2 ________ units are released

•

Lactose – milk sugar, major source of energy forinfants in mammals.

________ (intestine) – Glucose & Galactose

•Sucrose (glucose + fructose) – cane or beet sugarTable sugar, sweetener in all regular soft drinks

________ – Glucose & Fructose

Disaccharides are hydrolyzed by specific __________

http://en.wikipedia.org/wiki/Image:Sucrose-inkscape.svg

http://en.wikipedia.org/wiki/Image:Lactose3.png

http://en.wikipedia.org/wiki/Image:Maltose_structure.svg



Lactose intolerance ?

ommon among adults of most humans except___________ and parts of _______ ?

ctase (or -galactosidase) is low or missing in manyArabian,Jewish,Bantu,Japanese,Native Americans, and

Filipinoadults – are all _______________.



3. Catabolism of Monosaccharides

•Mannose – from breakdown of complex ________________.

•Galactose – from breakdown of _______.

•Fructose – from breakdown of sucrose.- Main sugar in _______ and _______



Mannose catabolism

Two enzymes convert mannose to __________________

1.hexokinase - Same enzyme that acts

on glucose

2. phosphomannoseisomerase

Fig 14.9

G l b li(From Lactose)



Three enzymes convert galactose to

_______________

1. Galactokinase 2. UDP-glucose: galactose 1-

phosphate uridylyltransferase 3. UDP-glucose 4-epimerase

Defect in any of the enzymesis cause of __________________.

Galactose catabolism( )



Problems in Galactose Metabolism

Infants lacking: hexose 1-phosphate uridylyltransferase

- have a form of _____________ - Must _______ milk and other sources of galactose.

Adults have galactose 1-phosphate uridylyltransferase which can metabolize galactose.

Some infants lack galactokinase– 2nd type of galactosemia

– _________ overcome as adults



Fructose (fruits) first getsconverted to Fructose 6-

phosphate and then enters ___________ .

Enzyme: ___________

This is major way of entry of Fructose in glycolysis in _____ and _________.

But different in _______ ,where most of Fructose iscatabolized.

Fructose catabolism



3 enzymes make glycolyticmetabolites

– ___________

– Fructose 1-PhosphateAldolase

– _____________

Fructose catabolismin Liver

C t b li f t f P t



Catabolic fates of Pyruvate

First route:Pyruvate _______.

Acetyl group is then oxidizedcompletely to CO2 by _______

_________________

Second route:Reduction to lactate via lactic

acid ___________

Third route:

leads to formation of _______ via ethanol ______________

1

23

F t f P t d A bi C diti



•Under hypoxic condition, NADH from glycolysis cannot be ______________ by O2.

•

•Non-availability of _____ as an electronacceptor for oxidation of G3-P can

__________ the Glycolysis.

Fate of Pyruvate under Anaerobic Conditions

F t f P t d A bi C diti



•Under these conditions, NAD+ is regenerated from _______ byreduction of pyruvate to _________ .

Lactate formationfavored ( ______ – G´)

______change inNAD+ or NADH


Fate of P ate nde Anae obic Conditions



Fermentation – 2 steps- I st step- Pyruvate decarboxylase requires Thiamin

pyrophosphate (TPP) (co-enzyme) and Mg2+

TPP is a coenzyme derived from vitamin ____ .

- Vitamin deficiencies leads to? ______- TPP has role in cleavage of bonds adjacent tocarbonyl group.

-

II nd step - Alcohol dehydrogenase requires - _____

Freely reversible





Summary

Glucose + 2ADP + 2Pi

__ lactate + 2 ATP + 2H2Oor

__ ethanol + 2 ATP + 2H2O


A b li f t f P t



Anabolic fate of Pyruvate

Pyruvate can also providecarbon skeleton for the synthesis of theamino acid ________ .

http://en.wikipedia.org/wiki/Image:Alanin_-_Alanine.svg



Gluconeogenesis

•Some mammalian tissue depend ________

glucose for their metabolic energy.

e.g. Human _____, nervous systems, renal medulla,

erythrocytes, embryonic tissue.

All need glucose from the blood as major /sole source of fuel.

Brain needs ~ _____ glucose/day whichis half of all the stored glucose.

Gl



Gluconeogenesis

•Body fluids carry only:

•~ ___g free glucose

• glycogen can provide 180-200 g of free

glucose.- Little more then a ___-day supply.

•Glucose if not obtained from the diet, body

must make _________ from the ____-carbohydrate precursors:

Gluconeogenesis

Gl i



Gluconeogenesis

•Gluconeogenesis occurs in _____- animals,- plants,- fungi and

- microorganisms.•Reactions are essentially ____ in all tissues

and all species.

Gl i



Gluconeogenesis

Biosynthesis of

carbohydrates

Glucogenicmolecules

Storage of

carbohydrates

S bst ates of Gl coneogenesis



Substrates of Gluconeogenesis

•Pyruvate, lactate and other non-carbohydrate

precursors can be substrates:•most of the ____________ ,• _______ and all the• _______cycle intermediates.

• Fatty acids are _____ the substrates in animals. • Lysine and Leucine are the only amino acids that

are ____ substrates.

Site of Gluconeogenesis in Animals



Site of Gluconeogenesis in Animals

•The organ which consumesmost of the

glucose e.g. brain and muscle,- carry out very little glucose __________.•

•Major site of gluconeogenesis in animals:

Liver : ___% Kidney : ___%

The synthesized glucose is released into

_____ which gets transported to the placeof need.

Gluconeogenesis Not merely of Glycolysis



Gluconeogenesis Not merely _____ of Glycolysis

In some ways gluconeogenesis

is reverse of glycolysis but not all steps are similar.

What is different?

Both are _____________ andoccur largely in _______ .

Reactions specific to Gluconeogenesis




___ different reactions in

gluconeogenesis.- Other ______ are same

as glycolysis.

Three different enzymecatalyzed reactions areutilized.

start here





1.First: Conversion of pyruvate to ____ : initiates gluconeogenesis.

Occurs in two unique steps: A.Pyruvate carboxylase

catalyzes first convertingpyruvate to oxaloacetate.

- First pyruvate is transportedto _____________.





Oxaloacetate + NADH + H+ L-malate + NAD+

Malate + NAD+ oxaloacetate + NADH + H+

Malate is transported out to _________ and isreoxidized to oxaloacetate.

Since oxaloacetate is required in cytosol but

it _________ be transported to cytosol. -so it is converted to_________by malate dehydrogenase.





B. Then PEP carboxykinase catalyzes the conversion of oxaloacetate to PEP in cytosol.

Reversible reaction buteffectively irreversibledue to ______ effectiveconcentration of PEP.

2nd specific reaction: Gluconeogenesis



2 specific reaction: Gluconeogenesis

Conversion of:

Fructose 1,6-bisphosphate to

Fructose 6-P

Catalyzed by _________ - Irreversible hydrolysis of

C-1 phosphate

3rd specific reaction : Gluconeogenesis



3. Conversion of Glucose 6-P to Glucose

catalyzed by Glucose 6-phosphatase requires Mg2+

Glucose is transported via _____ to brain and muscle.

3 specific reaction : Gluconeogenesis

Gluconeogenesis is a expensive but essential step



Gluconeogenesis is a expensive but essential step

2 Pyruvate + __ ATP+ ___ GTP+ __NADH + 2 H+ + 4 H2O

glucose + 4ADP + 2GDP + 6Pi + 2NAD+

P 556

P t Ph h t P th



Pentose Phosphate Pathway

- A __________ for producing NADPH: needed in synthesis of

• _________• _________

-Provides a pool of ribose5-phosphate for

synthesis of •

________ . 1

2

3

Pentose Phosphate Pathway: Starting point



Hexokinase – ATP & Mg2+

- ___ reversible (under intracellular condition) - Hexokinase is present in _______ of all organisms.

From Glycolysis: Phosphorylation of glucose

Pentose Phosphate Pathway: Starting point





Pentose phosphate pathway



1. Glucose 6-P dehydrogenase– requires _______ & Mg2+

Makes 6-phosphogluconolactone and ________ (1st molecule)

Genetic defect causes disease? Read. Common!

2. Lactonase– Mg2+

Makes 6-phosphogluconate

Oxidative Phase





Fig14

.21bottom

3. 6-Phosphogluconatedehydrogenase :

- requires NADP+ & Mg2+

- Products:

- ribulose 5-phosphate- _______ (2nd molecule)

4. Pentose phosphate isomerase:

- converts Ribulose 5-Pto itsisomer ________________

Oxidative Phase


Non-oxidative phase



Non oxidative phase

Pentose phosphate pathway: Non-oxidative phase



In tissue which primarily require NADPH:Pentose-P are recycled into ____________ .

-First step: epimerization of Ribulose 5-P to Xylulose 5-P- enzyme ribose 5-phosphate epimerase

Epimers?

Recycles PP to G6-P

Pentose phosphate pathway: Non oxidative phase

Non-oxidative phase Recycles PP to G6P



-Series of rearrangements of carbon skeletons:Six , 5-C sugar phosphates are converted to

_____ , 6-C sugar phosphates.

Non-oxidative phase Recycles PP to G6P



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3. CH 14 Glycolysis