Gluconeogenesis and the Pentose Phoshate Pathway Flashcards Preview

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Flashcards in Gluconeogenesis and the Pentose Phoshate Pathway Deck (20):
1

Malate shuttle provides way to transfer reducing equivalents (NADH) from mitochondrion to cytosol

•By means of malate shuttle, _________ produced in mitochondria is made available for this later step in cytosol, where it is low

•A different route is followed when lactate is the precursor

–Since NADH is produced in cytosol by LDH, shuttle unnecessary

–A mitochondrial PEP CK converts __________to ___________

NADH

oxaloacetate; PEP

2

Bypass #3: Glucose 6-phosphatase

•Five protein components

•Large negative DG; irreversible; enzyme is ________-activated

•Operative only in certain tissues (___________, __________, and ________); in other tissues, pathway stops at glucose 6-phosphate

–Lack enzyme; “want” to keep glucose as Glu-6-P, which cannot exit cell

•Phosphatase activity located on inner face of _________

•Glucose generated is transported out of cell via transporter _______

•What disorder is caused as result of a deficiency in Glu-6-phoshatase?

Mg2+

liver, kidney, small intestine lining

ER

GLUT2

Von Gierke’s (a GSD)

3

Where does the Pentose Phosphate Pathway Occur? What are the function in each location?

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4

How does Energy Charge  regulate pathways?

•Low E.C.

–_________[AMP]

–Glycolysis ______

•High E.C.

–Lots of ___________ present

–Biosynthetic reactions _________

–Gluconeogenesis __________

High

Stimulated

ATP

promoted

stimulated

5

Fates of Glucose

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6

The Three “Bypass” Steps of Gluconeogenesis

•Bypass steps catalyzed by:

–1)____________________

–2)_______________________

–3________________________

•Here, irreversible steps of glycolysis are being replaced

•Bypass #3 (G6Pase) occurs only in certain tissues:

–______________, ____________, and ____________

•First step occurs in ___________, but rest are in ____________

Pyruvate carboxylase and phosphoenolpyruvate carboxykinase (replace pyruvate kinase of glycolysis)

Fructose 1,6-bisphosphatase (replaces PFK-1)

–Glucose 6-phosphatase (replaces hexokinase)

Liver, kidney and epithelial cells of small intestine

mitochondrion;cytosol.

 

7

Pyruvate Carboxylase

•Located in ___________; a _________-dependent enzyme

•Pyruvate is either transported into mitochondrion or produced from _________ there

•Reaction occurs in two phases: (i) _________of biotin, and (ii) transfer of_________ group from _________ to ___________

•CO2 (HCO3- ) must be “activated” through ____________ first

•Absolute requirement for acetyl-CoA, a potent allosteric activator 

•A heterotetramer, each subunit contains 4 domains: a _____________ domain (phase 1); a pyruvate carboxylase domain (phase 2); a domain that binds acetyl-CoA; and the domain to which biotin is attached via _________ residue

mitochondrion; biotin

alanine

carboxylation;  CO2; carboxybiotin; pyruvate

phosphorylation

biotin carboxylation; pyruvate carboxylase; acetyl-CoA lysine

8

How is Glycerol Converted to a Glycolytic Pathway Intermediate (DHAP)?

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9

How does Fructose 2,6-bisphosphate regulate pathways?

•Acts mainly in __________

•Under starvation conditions

–What hormone is released?

–F2,6BP levels ___________

–Gluconeogenesis ____________

•In fed state

–What hormone is released?

–F2,6BP levels _______

–Glycolysis_________

liver

Glucagon

Decrease

stimulated (glucose is synthesized)

Insulin released

increase

stimulated 

10

Phase 2 of Pentose Phosphate Pathway

Non-oxidative Interconversion of Sugars

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11

What shuttle transports oxaloacetate from mitochondrion to cytosol?

The Malate-Aspartate Shuttle

12

PEP Carboxykinase

•Reaction:___________

•Located in _________

•Carries out _________and_________ oxaloacetate to give PEP

•Formation of unstable enol compound (__________) is driven by decarboxylation and is trapped by phosphorylation

–Is step reversible or irreversible?

–carboxylation-decarboxylation sequence is a way of __________pyruvate

Oxaloacetate + GTP → PEP + CO2 + GDP

cytosol

decarboxylation and phosphorylation; PEP

Irreversible

“activating”

13

The Pentose Phosphate Pathway

•Meets the needs of all organisms for __________, which is used for

–reductive biosynthesis of a number of important biomolecules

•Fatty acids

•Cholesterol and the steroid hormones

•nucleotides

•Neurotransmitters

–Protection against ______________arising from oxidative stress, which is especially important in __________ and ________ and _________

•Produces________, needed for synthesis of _______and ______, as well as the coenzymes ATP, NADH, FADH2 and coenzyme-A

–Especially important in rapidly __________cells such as __________, _________, and __________—also tumors

•Involves two phases: __________ and ___________

•Located in __________

NADPH

reactive oxygen species (ROSs)

erythrocytes; lens;cornea of  the eye

ribose-5-phosphate; DNA; RNA

dividing

bone marrow, skin, and intestinal mucosa

oxidative and non-oxidative

cytosol

14

The Importance of Reduced Glutathione for the Red Blood Cell

•Glutathione exists in two interconvertible forms: 2 GSH (red.) = GSSG (ox.)

•GSH protects against __________; it keeps RBCs in ________state (2 GSH = GSSG)

•GSSG converted to GSH via ___________, which uses ___________as cofactor

•ROSs cause cellular damage; especially harmful to _________

•GSH acts as “___________ buffer”:

–Maintains_________ residues of Hb in reduced state

–Keeps iron in reduced,__________, state

–_____________ peroxides and hydroxyl free radicals

•Otherwise: Hb tetramers-Heinz bodies-hemolysis-hemolytic anemia

ROSs

reduced

Glutathione Reductase; NADPH

RBCs

sulfhydryl

Cys

Fe2+

Detoxifies

15

How is the lactate that is produced during vigorous exercise dealt with?

 

•It is converted back to glucose via gluconeogenesis in the liver as part of the Cori Cycle.

16

Bypass #2: Fructose 1,6-bisphosphatase

•Replaces __________ of glycolysis

•Reaction equation: _________

•______-dependent; essentially irreversible

•Tightly and reciprocally controlled allosterically and hormonally

–When one pathway is “on,” the other is “off”

–Prevents uncontrolled___________,which wastes energy (6 – 2 = 4 NTPs)

 

PFK-1

Fructose 1,6-bisphosphate + H2O→ Fructose 6-phosphate + Pi

Mg2+

“futile cycling,”

17

The PPP Can also be Utilized to Mainly Produce Ribose Sugars. Process

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18

•There is no pathway by which glucose can be made from _______

acetyl-CoA

19

Phase 1: Oxidative Generation of NADPH

•Controlled by the _________-to- __________ ratio

–Ratio is normally very low

•Increased____________ causes NADP+ to rise, leading to allosteric activation of Glu6PDHase & greater flux through PPP

•When demand for NADPH slows, __________drops and _________slows

NADP+ ;NADPH

reductive biosynthesis

[NADP+];PPP  

20

Gluconeogenesis: An Introduction

–net synthesis of glucose from non-carbohydrate sources, including:

–pyruvate, lactate, glycerol, glucogenic amino acids (especially _________and __________ from muscle), TCA cycle intermediates (citrate, a-KG, succinyl-CoA, succinate, malate), propionyl-CoA

•Role:  to provide glucose for extrahepatic tissues (______________, ___________,_________,__________,___________, and _______) that require glucose as the main or only energy source

•_________ requires  ≈120 grams of glucose per day

–Glycogen stores can supply about half that amount.

•Overall Equation:

____________

•Where it Occurs in Body: ________, ___________, adn __________

alanine ;glutamine

(brain and nervous system, renal medulla, erythrocytes, testes, embryonic tissues

Brain

–2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 4 H2O      Glucose  + 4 ADP + 2 GDP + 2 NAD+ + 6 Pi

liver, renal cortex, epithelial cells of small intestinal lining