T04 - Pentose Phosphate Pathway Flashcards by Bhargav Arimilli

What are the primary products of the PPP? (3)

NADPH

ribose

5 or 7-carbon carbonhydrates

How well did you know this?

Not at all

Perfectly

Why is NADPH important? (2)

primary reducing power for biosynthetic pathways

protects against oxidative stress

How well did you know this?

Not at all

Perfectly

Pompe disease results from

recessively-inherited deficiency in alpha-glucosidase

How well did you know this?

Not at all

Perfectly

What is the function of the enzyme alpha-glucosidase?

digests glycogen to glucose

How well did you know this?

Not at all

Perfectly

What are the effects of Pompe disease?

buildup of glycogen in lysosomes, leading to muscle weakness and organ damage

fatal in infants if not treated within 2 years

How well did you know this?

Not at all

Perfectly

What are the linkages within glycogen?

glycosidic alpha-1,4 and alpha-1,6 linkages

How well did you know this?

Not at all

Perfectly

The alpha-glycosidic bonds within glycogen cause it to adopt what shape?

forms helical-like configuration

How well did you know this?

Not at all

Perfectly

What are the advantages of branches within glycogen? (2)

increased solubility

rapid release of glucose from glycogen

How well did you know this?

Not at all

Perfectly

What enzyme is responsible for releasing glucose from glycogen?

glycogen phosphorylase

How well did you know this?

Not at all

Perfectly

What enzyme is responsible for adding glucose to glycogen?

glycogen synthase

How well did you know this?

Not at all

Perfectly

What is the primary function of liver glycogen?

maintain blood glucose levels

How well did you know this?

Not at all

Perfectly

(T/F) Glycogen granules are absent from cells after a 24-hour fasting period.

True. Glycogen granules exist to maintain blood [glucose] between meals. If there are no meals, the glycogen granules are depleted.

How well did you know this?

Not at all

Perfectly

What is the primary function of muscle glycogen?

provide source of ATP in muscle

How well did you know this?

Not at all

Perfectly

What is the major limitation of muscle glycogen?

muscle glycogen is not available to other tissues because muscle cells don’t have glucose-6-phosphatase, which is required to make free glucose

How well did you know this?

Not at all

Perfectly

What molecule is the primer for glycogen synthesis?

the protein glycogenin is the primer/initiator of glycogen synthesis

How well did you know this?

Not at all

Perfectly

What molecule is the template (note: distinct from primer) for glycogen synthesis? Explain how this molecule forms.

glycosylated glycogenin is the template for glycogen synthase

“plain” glycogenin self-glycosylates by attaching glucose from UDP-glucose to its tyrosine residue

How well did you know this?

Not at all

Perfectly

What molecule is the building block for glycogen synthesis?

UDP-glucose

How well did you know this?

Not at all

Perfectly

Explain the difference between UDP-glucose and glucose.

UDP-glucose is an activated form of glucose because of high-energy diphosphate linkage → makes polymerization more energetically favorable

How well did you know this?

Not at all

Perfectly

How is UDP-glucose synthesized? What drives this synthesis forward?

UTP + G-1-P → UDP-glucose + PP_i, catalyzed by UDP-glucose pyrophosphorylase

irreversible hydrolysis of pyrophosphate drives reaction forward

How well did you know this?

Not at all

Perfectly

Which enzymes are responsible for the alpha-1,4 and alpha-1,6 linkages?

glycogen synthase adds in alpha-1,4 fashion

branching enzyme breaks alpha-1,4 linkages and replaces it with alpha-1,6 linkage

How well did you know this?

Not at all

Perfectly

In order for glycogen synthase to add UDP-glucose units, what structure must first exist in the glycogen molecule?

short pre-existing glucose polymer (4 units), which is synthesized by glycogenin

How well did you know this?

Not at all

Perfectly

Describe how the branching enzyme of glycogen synthesis operates.

transfers block of 7 residues to interior site

breaks alpha-1,4 bond and replaces it with alpha-1,6 linkage

interior site is located at least 4 residues from another branch site

[tip: think “July 4th” for 7 residues/4 residues]

How well did you know this?

Not at all

Perfectly

Write out the chemical equation for glycogen degradation/glycogenolysis.

(glycogen)_n + P_i → (glycogen)_n-1 + G-1-P

How well did you know this?

Not at all

Perfectly

What enzyme breaks alpha-1,4 glycosidic linkages in glycogen?

glycogen phosphorylase

How well did you know this?

Not at all

Perfectly

(T/F) G-1-P can freely diffuse across cell membranes.

**False**. It, like G-6-P, can't cross cell membranes because of the negative charge of the phosphate.

How is G-1-P liberated from glycogen made available for metabolic processes?

**phosphoglucomutase** converts G-1-P to G-6-P, which is the molecule at the center of glucose metabolism

What enzyme breaks alpha-1,6 glycosidic linkages in glycogen?

debranching enzyme

Describe how the debranching enzyme operates.

moves chain of 3 glucose residues to end of an adjacent glycogen branch breaks alpha-1,6 linkage of remaining residue remaining residue liberated as free glucose

The debranching enzyme is an example of what kind of enzyme?

debranching enzyme = example of **bifunctional** enzyme

What is the effect of epinephrine on glycogen? (2)

stimulates glycogenolysis in liver _and_ muscle [tip: think fight or flight]

Draw out the cascade of events that occurs when glucagon activates protein kinase A.

glucagon → adenylate cyclase → cAMP → active PKA → active phosphorylase kinase → active phosphorylase a → glycogenolysis

What is the effect of glucagon on glycogen?

glucagon stimulates glycogenolysis (to ensure there is adequate glucose for all tissues)

Which form of glycogen synthase is active — phosphorylated or dephosphorylated?

dephosphorylated is active [opposite of glycogen phosphorylase]

Which form of glycogen phosphorylase is active — phosphorylated or dephosphorylated?

phosphorylated form is active [opposite of glycogen synthase]

The low glucagon and epinephrine levels in the period after eating a meal activate what protein?

protein phosphatase 1 (PP1)

Protein phosphatase 1 (PP1) is activated/expressed in what period of time?

period of time after eating a meal, when glucagon and epinephrine levels are low

What is the function of protein phosphatase 1 (PP1)?

activates glycogen synthase (by dephosphorylation) inhibits glycogen phosphorylase (by dephosphorylation) [yes, both mechanisms are by dephosphorylation]

What does the term "favism" refer to?

refers to people who can't tolerate Fava beans

Favism results from what defect?

deficiency in G-6-P dehydrogenase (G6PDH)

What is the significance of the enzyme G6P dehydrogenase (G6PDH)?

rate-limiting enzyme of PPP

What is the rate-limiting enzyme of the PPP?

G6P dehydrogenase (G6PDH)

What happens if a patient with favism eats fava beans?

most likely, acute hemolysis

What are the symptoms of favism? (3)

jaundice black urine tired all the time

What is a benefit of favism?

malaria resistance, because RBC membrane is too compromised to allow propagation of malaria parasite

(T/F) Relatively speaking, the PPP consumes more glucose than glycolysis or glycogen synthesis.

**False.** The PPP consumes relatively _smaller_ amounts of glucose compared to glycolysis or glycogen synthesis.

Write out the overall reaction for the PPP.

G6P + 2 NADP⁺ → ribulose-5-phosphate + 2 NADPH + CO₂

Draw out the three steps of the PPP.

How does NADPH maintain the reductive environment of the cytosol? (2)

glutathione reductase uses NADPH to reduce glutathione dimers to just glutathione glutathione breaks disulfide bonds and maintains protein in reduced (-SH) state

How is NADPH utilized in anti-bacterial mechanisms?

NADPH provides electrons for generation of ROS by phagocytic cells (NADPH oxidase) to kill invading bacteria

How does NADPH protect cells from oxidative damage? Draw a diagram to support your answer.

glutathione peroxidase uses NADPH to convert H₂O₂ into water, which protects cells from oxidative damage

The PPP is most active in tissues involved in... Give three examples of such tissues.

fatty acid and steroid synthesis for example: liver adrenal gland adipose tissue

Why is the PPP important in the eye?

cornea and lens lack mitochondria (therefore no TCA cycle) and have limited blood supply, so they use the PPP to metabolize glucose

Why is the PPP important in RBCs? (2)

RBCs lack mitochondria (so no TCA cycle), making the PPP _the only source of NADPH_ in RBCs RBCs are susceptible to oxidative damage, which the PPP can help prevent

What is the most common enzyme disorder in the world?

G6P dehydrogenase deficiency

What is the most abundant small peptide in human cells?

glutathione

What is the treatment for Pompe disease?

myozyme (recombinant acid alpha-glucosidase)

Which two tissues have the highest concentration of glycogen in the body?

liver (5-10% of wet weight) muscle (1-2% of wet weight)

(T/F) Fat can be converted to glucose.

**False**

In the polymerization reaction of glycogenesis, what serves as the leaving group?

UDP

Write out the net chemical equation for glycogenesis/glycogen synthesis.

G6P + ATP + (glycogen)_n + H₂O → (glycogen)_n+1 + ADP + 2 P_i

How does glycogen phosphorylase break alpha-1,4 glycosidic linkages in glycogen?

uses inorganic phosphate to cleave the alpha-1,4 linkages

What is the defect in Von Gierke's disease?

glucose-6-phosphatase mutation

What are the effects of von Gierke's disease?

hypoglycemia increased glycogen storage → hepatomegaly lactic acidosis

What is the most common treatment for von Gierke's disease?

daily cornstach intake to prevent hypoglycemia

Where in the cell does the PPP take place?

cytoplasm

Does the PPP require ATP?

No.