Chapter 4: Cellular Metabolism

Question 1

Anabolism vs catabolism

Answer 1

1. Anabolism: building (main end products are lipids, amino acids, carbs, nucleotides), endergonic
2. Catabolism: breakdown (main end products are CO2, H2O, NH3), exergonic
   2a. Oxidative process bc it results in the oxidation of carbon’s in Biomolecules

Question 2

3 important energy carriers

Answer 2

1. Nucleoside triphosphates (Ex: ATP, GTP, etc): To drive rx forward, ATP releases energy through ATP hydrolysis or phosphoryl group transfer
2. Dinucleotides (NADH, and FADH2): Strong reducing agents that results in the generation of ATP
3. Dinucleotide phosphates (NADPH): Strong reducing agents that drives anabolic reactions like the synthesis of fatty acids and nucleotides

Question 3

Aerobic respiration overview

Answer 3

1. Glycolysis: Entirely in cytosol, Anaerobic , Products: 2 pyruvate, 2ATP, 2NADH
2. PDC: decarboxylation of pyruvate by PDC which forms acetyl CoA and NADH… acetyl coa transfers 2C to oxaloacetate forming citrate
3. Krebs cycle: 2 pyruvate each get 3NADH, 1FADH2, 1GTP
4. ETC: NADH, FADH2 pass their electrons to ETC: 2.5ATP/NADH and 1.5ATP/FADH2

Question 4

Glycolysis overview

Answer 4

1. Location: cytosol
2. Sum of products from glucose: 2ATP, 2NADH, 2H+, 2 pyruvate
3. Steps with hexokinase, PFK, and pyruvate kinase are all irreversible
4. Always starts with glucose

Question 5

Glycolysis steps

Answer 5

1. Glucose -> G6P via hexokinase (use ATP: irreversible)
2. G6P <-> F6P via phosphohexose isomerase
3. F6P -> F1,6BP via PFK-1 (use ATP: Irreversible: rate limiting step)
4. F1, 6BP <-> DHAP + G3P cleaved via aldolase
5. DHAP <-> G3P via triose phosphate isomerase
6. G3P<-> 1, 3BPG via G3P dehydrogenase (generates NADH, H+)
7. 1,3BPG <-> 3PG via phosphoglycerate kinase (generates ATP)
8. 3PG <-> 2PG via phosphoglycerate mutase
9. 2PG <-> PEP via enolase
10. PEP -> Pyruvate via pyruvate kinase (generates ATP: Irreversible)

Question 6

Glycolysis regulation

Answer 6

1. High glycolysis: when low ATP/high AMP, high glucose (high insulin)
   1a. F6P is converted to F2, 6BP by PFK2= F2,6BP activated PFK1 to convert F6P to F1,6BP
2. Low glycolysis: high ATP inhibits PFK which leads to high G6P (F6P and G6P in high equilibrium) to inhibit hexokinase as negative feedback

Question 7

Fermentation

Answer 7

1. Yeast: Pyruvate from glycolysis -> acetylaldehyde + CO2 (via pyruvate decarboxylase) -> ethanol + NAD+ (via alcohol dehydrogenase)
2. Animals: Pyruvate from glycolysis -> lactate + NAD+ (via lactate dehydrogenase)
3. Main purpose of fermentation is to regenerate NAD+ to enter glycolysis again to get more ATP

Question 8

Gluconeogenesis overview

Answer 8

1. Main substrates: pyruvate, lactate, glycerol, glucogenic amino acids (any 3 carbon, non hexose precursors)
2. Active when fasting (high glucagon, low glucose)

Question 9

Gluconeogenesis steps

Answer 9

1. Bypass 1: pyruvate ->oxaloacetate (via pyruvate carboxylase) goes into cytoplasm ->PEP (via PEPCK)
   1a. PEP->2PG->3PG->1,3BP->G3P->DHAP->F1,6BP
2. Bypass 2: F1,6BP -> F6P (via fructose 1,6 bisphosphatase)
   2a. F6P->G6P
3. Bypass 3: G6P to glucose (via glucose 6 phosphatase)

Question 10

Gluconeogenesis /glucose regulation:

Answer 10

1. Glycolysis occurs when: high F2,6BP, AMP, F1,6BP
2. Gluconeogenesis occurs when: high citrate, acetyl coa

Question 11

Glycogenolysis

Answer 11

1. Irreversible Breakdown of glycogen one glucose residue at a time to glucose 1 phosphate via glycogen phosphorylase (G1P)
2. Steps:
   2a. Glycogen -> G1P via glycogen phosphorylase (adds a phosphate)
   2b. G1P->G6P via phosphoglucomutase
   2c. G6P can enter many processes to be converted to glucose

Question 12

Regulation of glycogenolysis

Answer 12

1. Liver: glycogen phosphorylase is active when low glucose (high glucagon and epinephrine)
2. Muscle: epinephrine and Ca2+ activate PK which activates glycogen phosphorylase which activates glycogenolysis in muscle…. (When active=low glucose level=more glycogenolysis)

Question 13

Glycogenesis process

Answer 13

1. When high insulin (from beta pancreatic)=Addition of glucose to non reducing end of glycogen =storage of glucose
2. Process
   2a. G6P->G1P via phosphoglucomutase
   2b. G1P -> UDP-glucose via UDP glucose pyrophosphorylase
   2c. UDP glucose -> glycogen via glycogen synthase

Question 14

Lactic acid cycle (Cori cycle) in Fermentation

Answer 14

1. When there is a cycle between fermentation and glycolysis:
   1a. Glucose undergoes glycolysis to make pyruvate -> fermentation to make lactate (regenerates NAD+ for glycolysis to continue fermentation)
   1b. Excess lactic acid goes to liver which undergoes gluconeogenesis to get glucose to go back to muscle for more fermentation

Question 15

Pentose phosphate pathway (PPP) functions

Answer 15

1. Energy capture: via reduction of NADP+ to NADPH
   1a. NADPH is a reducing agent used to synthesize cholesterol, steroids, fatty acid in cytosol
   1b. NADPH also rereduces GSH to scavenge for ROS
2. Ribose 5 phosphate synthesis for production of nucleotides

Question 16

PPP stages: in cytosol

Answer 16

1. Oxidative phase: irreversible (produces 2 NADPH)
   1a. G6P ->->ribulose 5 phosphate + CO2 +2NADPH
2. Non oxidative pathway:
   2a. Ribulose 5 phosphate -> ribose 5 phosphate (for nucleotides)—> G3P + F6P
   2b. G3P and F6P: feed into glycolysis (for ATP), gluconeogenesis (for more G6P)

Question 17

Shuttles to get NADH through the mitochondrial matrix

Answer 17

1. Malate aspartate shuttle (heart, liver, kidneys): NAD+ is oxidized to NADH+ bc it reduces oxaloacetate to malate…malate goes to matrix and is oxidized back to oxaloacetate which reduces NAD+ to NADH
2. Glycerol phosphate shuttle (muscle, brain): DHAP -> NADH+ + Gro3P -> DHAP + FADH2

Question 18

Aerobic respiration: PDH complex

Answer 18

1. Pyruvate goes from cytosol (glycolysis) into matrix
2. In matrix, pyruvate is irreversible converted to acetyl coa via PDC which produces NADH and CO2
   2a. Pyruvate + NAD+ CoA -> acetyl CoA
   + CO2, + NADH + H+ (via pyruvate dehydrogenase: decarboxylation, oxidation, transfer of coa)
   2b. Acetyl coa can then go to TCA to make CO2 or undergo FAS to make fatty acids
3. PDH active: insulin which dephophoylates (phosphatase) PDH to activate it, high pyruvate, high ADP

Question 19

Krebs cycle

Answer 19

1. Acetyl coa + Oxaloacetate -> citrate (via citrate synthase)
2. Citrate -> isocitrate (via aconitase)
3. Isocitrate -> alpha ketoglutarate, CO2, NADH (via isocitrate dehydrogenase)
4. Alpha keto glutarate -> succinyl coa, CO2, NADH (via alpha ketoglutarate dehydrogenase)
5. Succinyl coa -> succinate, GTP (via succinyl coa synthetase)
6. Succinate-> fumarate, FADH2 (succinate dehydrogenase)
7. Fumarate -> malate (fumerase)
8. Malate ->oxaloacetate, NADH (malate dehydrogenase)

Question 20

Anaplerotic sequence

Answer 20

1. The need to replace oxaloacetate is done via pyruvate being able to become oxaloacetate via pyruvate carboxylase

Question 21

ETC

Answer 21

1. 4 integral proteins and 2 electron carrier molecules (coenzyme Q (hydrophobic) and cytochrome c (water soluble) in inner membrane
2. From Krebs cycle:
   2a. NADH goes complex 1 (contains flavoprotein), 3, 4: 10H+
   2b. FADH2 goes complex 2 (contains flavoprotein), 3, 4: 6H+ (complex 2 generates no H+)
   2c. All electrons are accepted by complex 4’s oxygen to make water
3. H+ from NADH, FADH2 create proton motive gradient in the intermembrane space which powers ATP synthase to generate ATP (3H+=1ATP) in oxidative phosphorylation
4. If there are many uncoupling proteins (UPC) on the mitochondria, it will diminish the proton motive force and not generate ATP (high metabolism /skinny people)

Question 22

ATP synthase

Answer 22

1. Proton motive force from inter membrane space push H+ into F0 which spins the F1 allowing it to generate 1ATP/3H+

Question 23

Oxidative phosphorylation energy

Answer 23

1. 2.5 ATP/NADH ; 1.5 ATP/FADH2
2. Whole process generates 36ATP
   2a. Glycolysis 6ATP, PDH 6ATP, Krebs cycle 24ATP

Question 24

Fatty acid catabolism/ beta oxidation: mitochondria and peroxisomes

Answer 24

1. Fatty acid activation: fatty acid + CoA-SH + ATP->formation of acyl CoA via acyl coa synthase (ACS)
2. Transport of acyl coa into mitochondria:
   2a. Acyl coa + carnitin -> acyl carnitine + HSCoA (via CPT1)
   2b. Acyl carnitine in
   2c. Acyl carnitin to acyl coa via CPT2
3. Acyl coa in matrix: beta oxidation: Shortening of fatty acyl coa (CN->C(N-2))
   3a. Oxidation: Fatty acyl coa -> trans enoyl coa + FADH2
   3b. Hydration: trans enoyl coa + FADH2 -> 3 hydroxyacyl coa
   3c. Oxidation: 3 hydroxyacyl coa -> B-ketoacyl coa + NADH
   3d. Thiolysis: B-ketoacyl coa + NADH-> fatty acyl coa + acetyl coa

Question 25

Fatty acid synthesis

Answer 25

1. Exportation: 1a. Acetyl coa (matrix) + oxaloacetate -> citrate 1b. Citrate -> acetyl coa + oxaloacetate in cytosol 2. Acetyl coa + co2 -> malonyl coa (ACC) 3. Malonyl coa + acetyl coa —-> palmitic acid (16C)

Question 26

Ketogenesis

Answer 26

1. Occurs in low blood sugar (fasting) or diabetes in liver: low insulin 2. Acetyl coa made from (FAS, or glycolysis etc) gets made into ketone bodies: acetoacetate, acetone, D-B-hydroxybutyrate 3. These ketone bodies then travel to other cells so they can break them down for energy

Question 27

Amino acid degradation

Answer 27

1. As a last resort we break down proteins into amino acids which can feed into the citric acid cycle at various time points