BIOMG3310 Quiz 8 (Lectures 28-30)

Pyruvate Dehydrogenase Complex

pyruvate + CoA + NAD+ --> acetyl-CoA + CO2 + NADH

Pyruvate Kinase (PK) catalyzes the 1. ____ step of 2._____, converting 3._______ -> pyruvate, producing 4. _____

-final

-glycolysis

-PEP

-ATP

What is the regulation of PK?

-activated by F 1,6 BP (feed-forward activation)

-Inhibited by ATP, alanine, and acetyl-CoA (signals that energy and biosynthetic precursors are abundant)

Regulation of PK in the liver

-hormonally regulated via phosphorylation by PKA

-Glucagon -> Activates PKA -> phosphorylates PK -> inhabits glycolysis (to favor gluconeogenesis)

-> Insulin -> dephosphorylates PK -> activates glycolysis

What is the purpose of the Pentose Phosphate Pathway (PPP)?

-produces NADPH (for biosynthesis and antioxidant defense)

-produces ribose-5-phosphate (for nucleotide synthesis)

When is the Pentose Phosphate Pathway activated?

-when energy needs are met but biosynthetic needs are high - i.e., in liver, adipose tissue, adrenal glands, gonads, lactating mammary glands, and rapidly dividing cells

-activated by high G-6-P and need for NADPH or nucleotides

What is the connection of the Pentose Phosphate Pathway to glycolysis?

-begins with glucose-6-phosphate (G6P), which can enter either glycolysis or the PPP

-G6P dehydrogenase oxidizes G6P -> 6-phosphogluconate, producing NADPH

-Intermediates can re-enter glycolysis (e.g., fructose-6-P or glyceraldehyde-3-P)

Short, intense activity (sprint) relies on

substrate-level phosphorylation in glycolysis (fast ATP but low yield)

Long-term activity (marathon) relies on

oxidative phosphorylation (slow but sustained high yield)

Anaerobic conditions limit NAD+ regeneration, so glycolysis depends on

lactate fermentation to regenerate NAD+

Why Pyruvate -> Lactate during intense exercise? (~4 min run)

-oxygen becomes limiting; electron transport chain slows, and NADH accumulates

-to regenerate NAD+ pyruvate is reduced to lactate by lactate dehydrogenase

-this allows glycolysis to continue producing ATP anaerobically, albeit inefficiently

Chemical equation for the reaction where pyruvate is converted to lactate

Pyruvate + NADH + H+ -> Lactate + NAD+

Pyruvate Dehydrogenase (PDH) Complex

-location: mitochondrial matrix

-purpose: links glycolysis -> Citric Acid Cycle (CAC)

Pyruvate Dehydrogenase (PDH) Complex Overall Reaction

Pyruvate + CoA + NAD+ -> Acetyl-CoA + CO2 + NADH + H+

Pyruvate Dehydrogenase (PDH) Complex Step 1

-Pyruvate Dehydrogenase (Decarboxylation)

-Cofactor: Thiamine pyrophosphate (TPP, derived from Vitamin B1)

-removes CO2 , forms hydroxyethyl-TPP intermediate

Pyruvate Dehydrogenase (PDH) Complex Step 2

-Dihydrolipoyl Transacetylase (Acetyl Transfer)

-cofactor: lipoamide (attached to lysine "swinging arm"

-transfers the acetyl group to Coenzyme A (CoA, vitamin B5)

Pyruvate Dehydrogenase (PDH) Complex Step 3

-dehydrolioyl dehydrogenase (redox Reset)

-cofactors: FAD (vitamin B2) and NAD+ (vitamin B3)

-regenerates oxidized lipoamide and produces NADH

PDH Complex Channeling

intermediates pass directly between enzyme sites via lipoamide "arms", preventing diffusion and side reactions

PDH Complex: Why it matters?

-Produces NADH (for oxidative phosphorylation) and acetyl-CoA (for CAC & biosynthesis)

-Thiamine deficiency (B1) impairs PDH -> leads to accumulation of pyruvate and lactate (e.g., Beri-Beri, Wernicke-Korsakoff)

Key Vitamins of PDH complex

-B1 (Thiamine) -> TPP

-B2 (riboflavin) -> FAD

-B3 (Niacin) -> NAD+

-B5 (Pantothenic acid) -> CoA

What is the overall reaction of the citric acid cycle?

Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O -> 2CO2 + 3NADH + FADH2 + GTP + 2H+ + CoA

Citric Acid Cycle (CAC) - Overview

Also called the Krebs Cycle or TCA Cycle, the CAC completes the oxidation of glucose by oxidizing acetyl-CoA to CO2 within the mitochondrial matrix. It generates high-energy electrons carriers (3 NADH, 1FADH2) and 1GTP/ATP per acetyl-CoA that feed into oxidative phosphorylation

Overall reaction

Each glucose molecule yields two turns of the CAC (one per acetyl-CoA).

Step 1

-Citrate Synthase

-condensation of acetyl-CoA (2C) with oxaloacteate (4C) -> citrate (6C).

-Highly exergonic

-Regulated step

Step 2a-2b

-Aconitase

-dehydration -> cis-aconitate -> hydration to isocitratre

-converts teritiary -> secondary alcohol to prepare for oxidation

Step 3

-Isocitrate dehydrogenase

-oxidative decarboxylation: isocitrate -> α-ketoglutarate + CO₂ + NADH

-Regulated step

-Output: 1 NADH, 1 CO2

Step 4

-α-Ketoglutarate Dehydrogenase Complex

-Similar mechanism to PDH complex: α-ketoglutarate → succinyl-CoA + CO₂ + NADH

-Regulated step

-Output: 1 NADH, 1 CO2

Step 5

-Succinyl-CoA synthetase

-Subtrate-level phosphorylation

-Thioester bond drives conversion of GDP + Pi -> GTP and succinyl-CoA -> succinate

-Output: 1 GTP

Step 6

-Succinate Dehydrogenase

-Membrane-bound enyme; oxidation of succinat -> fumarate; reduction of FAD _> FADH2

-Output: 1 FADH2

Step 7

-Fumarase

-Hydration of fumarate -> malate

Step 8

-Malate dehydrogenase

-oxidation of malate -> oxaloacetate, regenerating the starting compound

-1 NADH

What are the regulated steps?

-Citrate Synthase (ΔG ≈ -50 kJ/mol)

-Isocitrate Dehydrogenase (ΔG ≈ -20 kJ/mol)

-α-Ketoglutarate Dehydrogenase (ΔG ≈ -45 kJ/mol)

Why is the Citric Acid Cycle considered amphibolic?

Because it serves both catabolic (energy-yielding) and anabolic (biosynthetic) roles - breaking down acetyl-CoA for energy while providing intermediates for biosynthesis

What biosynthetic pathways use intermediates from the Citric Acid Cycle?

-citrate -> fatty acid & sterol synthesis

-α-Ketoglutarate → amino acid (glutamate) synthesis

-Syccinyl-CoA -> heme synthesis

-Oxaloacetate/Malate -> gluconeogenesis or amino acid synthesis

What are anaplerotic reactions and why are they important for the CAC?

they are replenishing reactions that regenerate CAC intermediates when they're used in other pathways - e.g., pyruvate or PEP + CO2 -> oxaloacetate or malate via pyruvate carboxylase or PEP carboxynase

Why do fats need special transport in the body?

fats are insoluble in water, so they must be emulsified and packaged to travel through the body

What do bile salts do during fat digestion?

Bile salts from the liver/gallbladder emulsify fat, breaking it into small droplets for enzymes to act one

What enzymes breaks down trialglycerols (TAGs)?

Lipases in the small intestine hydrolyze TAGs into free fatty acids and monoacylglycerols

What are micelles and why are they important?

Micelles are tiny lipid-bile salt particles that carry fatty acids to intestinal cells for absorption

What happens to fatty acids inside intestinal cells?

They are re-assembled into TAGs and packaged into chylomicrons

What are chylomicrons?

Large lipid particles that transport TAGs through lymph and blood to tissues

How do fatty acids leave chylomicrons to enter cells?

Lipoprotein lipase on capillary walls hydrolyzes TAGs, releasing fatty acids into nearby cells

What can happen to fatty acids inside tissue cells?

They can be oxidized for energy or re-esterified for storage as fat

Is the transport of dietary fat regulated?

No - it's unregulated; dietary fat automatically becomes body fat or fuel

Small intestine lumen

-TAG hydrolysis

-Lipase breaks down dietary TAGs

Intestinal epithelial cell

-TAG reassembly

-FA + glycerol -> TAG (for chylomicron packaging)

Capillary walls

-TAG hydrolysis again

-Lipoprotein lipase releases FAs to tissues

Tissue cells

-TAG reassembly or oxidation

-FAs used for ATP or stored as fat