ch 18 practice Q's PDH COMPLEX

BIOCHEM unit 3

vitamin B1 (thiamine) deficiency would affect PDH complex activity

• true

• false

true

thiamine is the precursor to TPP, an essential cofactor for E1. without adequate thiamine, PDH complex activity decreases, leading to neurological symptoms.

The PDH complex uses substrate channeling to improve efficiency

• true

• false

true

substrate channeling allows intermediates to be passed directly between active sites without diffusing into solution, increasing efficiency and preventing side reactions

the PDH complex links glycolysis to the TCA cycle

• true

• false

true

the PDH complex is the critical bridge between glycolysis (which produces pyruvate) and the TCA cycle (which required acetyl-CoA), making it essential for complete glucose oxidation.

the overall reaction catalyzed by the PDH complex produces:

A. Pyruvate + CoA + NADH

B. Acetyl-CoA + NADH + CO₂

C. Lactate + NAD⁺

D. Glucose + ATP

B. Acetyl-CoA + NADH + CO2

the PDH complex convert pyruvate into acetyl-CoA while releasing CO2 and reducing NAD+ to NADH, linking glycolysis to the TCA cycle

the PDH complex reaction is reversible under physiological conditions

• true

• false

false

the PDH complex reaction is essentially irreversible under physiological conditions due to the large negative ΔG, which is why its regulation is so critical.

which enzyme in the PDH complex uses thiamine pyrophosphate (TPP) as a cofactor?

A. E3 (dihydrolipoyl dehydrogenase)

B. E1 (pyruvate dehydrogenase)

C. E2 (dihydrolipoyl transacetylase)

D. E1 (pyruvate transacetylase)

B. E1 (pyruvate dehydrogenase)

E1 uses TPP (derived from vitamin B1) to facilitate the decarboxylation of pyruvate, which is the first step in the PDH complex reaction.

the pyruvate dehydrogenase complex is located in the:
A. mitochondrial matrix

B. mitochondrial intermembrane space

C. endoplasmic reticulum

D. cytosol

A. Mitochondrial matrix

the PDH complex is indeed located in the mitochondrial matrix, where it can immediately supply acetyl-CoA to the TCA cycle that are also in this compartment.

phosphorylation of the PDH complex activates it

• true

• false

false

phosphorylation actually inactivates the PDH complex. This is an important regulatory mechanism that shuts down pyruvate oxidation when it’s not needed

the PDH complex consists of how many different enzymes?

A. five

B. two

C. three

D. four

A. Five

E1 - thymine pyrophosphate (TPP)

E2 - lipoic acid

E3 - FAD

additional: CoA, NAD+

lipoic acid is covalently attached to which enzyme

A. E3

B. E2

C. E1

D. PDH kinase

B. E2

lipoic acid is attached to lysine residues on E2, where it acts as a swinging arm to shuttle intermediates between the active sites of E1, E2, and E3

a researcher measures PDH complex activity in liver tissue from fed vs fasted rats. compared to fed rats, the fasted rats would most likely show:

A. Higher PDH complex activity only if glucose is available

B. Higher PDH complex activity due to increased energy demand

C. No difference in PDH complex activity

D. Lower PDH complex activity due to PDH kinase activation

D. lower PDH complex activity due to PDH kinase activation

during fasting, elevated fatty acid oxidation increases acetyl-CoA and NADH, activating PDH kinase to shut down the complex and spare glucose for the brain.

Assign each enzyme its prosthetic group:

E1

E2

E3

1 TPP (decarboxylation)

2 lipoic acid (swinging arm)

3 FAD (regenerates oxidized lipoic acid)

The E1 enzyme used BLANK to decarboxylate pyruvate, then transfers the resulting group to BLANK acid attached to the E2 enzyme, which subsequently transfers an BLANK group to BLANK to form the final product.

TPP/lipoic/acetyl/CoA

high levels of acetyl-CoA and NADH would

A. have no effect on complex regulation

B. activated the PDH phosphatase, turning on the complex

C. only affect E1 enzyme activity

D. activate PDH Kinase, shutting down the complex

D. activate PDH kinase, shutting down the complex

high acetyl-CoA and NADH signal energy sufficiency, activating PDH kinase to phosphorylate and inactivate the complex, preventing wasteful pyruvate oxidation.

In the fed state, BLANK activates PDH BLANK, which removes BLANK groups from the E1 enzyme, resulting in an BLANK PDH complex that promotes glucose oxidation.

insulin/phosphatase/phosphate/active

a patient with chronic alcoholism develops neurological symptoms. thiamine supplementation improves their condition. this is most likely because thiamine deficiency affects:

A. the PDH complex E1 enzyme

B. lactate production

C. fatty acid oxidation

D. glucose transport into cells

A. the PDH complex E1 enzyme

alcoholics often develop thiamine deficiency, which impairs the E1 enzyme’s ability to use TPP, reducing PDH complex activity and causing neurological damage due to decreased brain energy metabolism

arsenic poisoning affects the PDH complex by:

A. binding to lipoic acid on E2

B. activating PDH kinase

C. competing with NAD+ for E3

D. inhibiting TPP binding to E1

A. binding to lipoic acid on E2

arsenic binds tightly to the sulfhydryl groups on lipoic acid, preventing it from functioning properly and blocking the PDH complex reaction

in the fed state, insulin promotes

A. PDH kinase activation

B. PDH phosphatase activation

C. fatty acid oxidation

D. gluconeogenesis

B. PDH phosphatase activation

insulin signals glucose abundance and promotes PDH phosphatase activation, which dephosphorylates and activates the PDH complex to oxidize the incoming glucose

during exercise, increased calcium levels activate PDH phosphatase. this would result in:

A. decreased acetyl-CoA production

B. enhanced pyruvate oxidation

C. reduced energy production

D. increased glucose storage

B. enhanced pyruvate oxidation

activation of PDH phosphatase removes phosphate groups from the complex, activating it and increasing pyruvate oxidation to meet the energy demands of exercise.

a patient has a genetic defect causing E2 enzyme deficiency. compared to normal individuals, this patient would most likely have:

A. Normal acetyl-CoA levels and lower lactate

B. Higher acetyl-CoA levels and normal lactate

C. Higher acetyl-CoA levels and higher lactate

D. Lower acetyl-CoA levels and higher lactate

D. lower acetyl-CoA levels and higher lactate

E2 deficiency blocks acetyl-CoA production, causing pyruvate to accumulate and be converted to lactate instead, resulting in lactic acidosis

a researcher develops a drug that specifically inhibits PDH kinase. in muscle tissue, this drug would most likely:
A. Decrease glucose utilization and increase fatty acid oxidation

B. Have no effect on fuel utilization

C. Only affect the complex during fasting conditions

D. Increase glucose utilization and decrease fatty acid oxidation

D. increased glucose utilization and decreased fatty acid oxidation

inhibiting PDH kinase would prevent phosphorylation of the complex, keeping it active and promoting glucose oxidation even when fatty acids are available.

PDH complex deficiency is often treated with a ketogenic diet because:

A. ketones provide an alternate source of acetyl-CoA

B. ketones can repair the defective enzyme

C. the diet increases PDH complex expression

D. the diet provides thiamine to restore enzyme function

A. ketones provide an alternate source of acetyl-CoA

ketones can be converted directly to acetyl-CoA without requiring the PDH complex, bypassing the defect and providing the TCA cycle with substrate

scenario: A patient with complete PDH complex deficiency cannot convert pyruvate to acetyl-CoA

true or false: this patient’s muscle cells during exercise would show increased lactate production compared to normal individuals, AND their liver would be unable to convert this lactate back to glucose via gluconeogenesis, creating a dangerous metabolic situation

false

consider whether the liver’s ability to perform gluconeogenesis depends on the PDH complex

compare the metabolic effects of PDH complex deficiency versus pyruvate kinase (PK) deficiency (note: pyruvate kinase is the enzyme from glycolysis, not PDH kinase!)

A. PDH deficiency causes low lactate; PK deficiency causes lactic acidosis

B. neither would significantly affect lactate levels

C. PDH deficiency causes lactic acidosis; PK deficiency causes low lactate

D. both would cause lactic acidosis

C. PDH deficiency causes lactic acidosis; PK deficiency causes low lactate

PDH deficiency causes pyruvate to accumulate and convert to lactate. in contrast, PK deficiency reduces pyruvate production, so there’s less substrate available for lactate formation.

a pharmaceutical company develops PDH-kinase inhibitor “Drug X“ for diabetes treatment. A type 2 diabetic patient takes Drug X with breakfast (high carbohydrate meal). two hours after breakfast, the patient’s liver cells would most likely show:
A. high PDH activity and high gluconeogenesis, depleting glucose rapidly

B. high PDH activity and low gluconeogenesis, promoting glucose utilization

C. low PDH activity and low gluconeogenesis, blocking all glucose metabolism

D. low PDH activity nd high gluconeogenesis, conserving glucose.

B. high PDH activity and low gluconeogenesis, promoting glucose utilization

the drug keeps PDH active (by blocking kinase), promoting glucose oxidation. combined with insulin from the meal, gluconeogenesis would be suppressed, creating ideal glycolytic conditions.

during prolonged fasting, the PDH complex is inactivated while gluconeogenesis is activated. this metabolic coordination ensures

A. glucose is conserved for the brain and red blood cells while other tissues use fatty acids

B. rapid depletion of glycogen stores

C. maximum ATP production from all available substrates

D. equal utilization of glucose and fatty acids by all tissues

A. glucose is conserved for the brain and red blood cells while other tissues use fatty acids

this demonstrates understanding of metabolic priorities. inactivating PDH while activating gluconeogenesis spares glucose-dependent tissues (brain, RBCs) whole allowing other tissues to oxidize fatty acids

in muscle during intense exercise, both glycolysis and the PDH complex are highly active. this coordination is achieved by:

A. epinephrine activating all glycolytic enzymes

B. high ATP levels activating both pathways

C. low oxygen levels stimulating glucose metabolism

D. low energy charge activating phosphofructokinase-1 and PDH phosphatase

D. low energy charge activating phosphofructokinase-1 and PDH phosphatase

low energy charge (low ATP/AMP ration) and increased Ca2+ during exercise activate both PFK-1 (speeding glycolysis) and PDH phosphatase (activating PDH), creating coordinated glycose oxidation

a researcher studies metabolic coordination by measuring enzyme activities in liver cells transitioning from faster to fed state. in fasted state: PDH is phosphorylated (inactive), gluconeogenic enzymes are active. after a high-carb meal with insulin release, which sequence correctly describes the metabolic shift?

A. PDH kinase activates → PDH becomes more phosphorylated → gluconeogenesis increases → glucose is produced

B. Insulin has no effect on PDH → only gluconeogenesis changes → acetyl-CoA levels remain constant

C. PDH remains phosphorylated → gluconeogenesis remains high → glucose-6-phosphatase stays active → blood glucose rises

D. PDH phosphatase activates → PDH becomes dephosphorylated → PFK-2 is dephosphorylated → F-2,6-BP increases → gluconeogenesis is suppressed

D. PDH phosphatase activates → PDH becomes dephosphorylated → PFK-2 is dephosphorylated → F-2,6-BP increases → gluconeogenesis is suppressed

insulin activated phosphatase (activating PDH), dephosphorylated PFK-2 (increasing, F-2,6-BP, which simultaneously activates glycolysis and inhibits gluconeogenesis