Chapter 4: Cellular Metabolism Flashcards
1
Q
Anabolism vs catabolism
A
- Anabolism: building (main end products are lipids, amino acids, carbs, nucleotides), endergonic
- Catabolism: breakdown (main end products are CO2, H2O, NH3), exergonic
2a. Oxidative process bc it results in the oxidation of carbon’s in Biomolecules
2
Q
3 important energy carriers
A
- Nucleoside triphosphates (Ex: ATP, GTP, etc): To drive rx forward, ATP releases energy through ATP hydrolysis or phosphoryl group transfer
- Dinucleotides (NADH, and FADH2): Strong reducing agents that results in the generation of ATP
- Dinucleotide phosphates (NADPH): Strong reducing agents that drives anabolic reactions like the synthesis of fatty acids and nucleotides
3
Q
Aerobic respiration overview
A
- Glycolysis: Entirely in cytosol, Anaerobic , Products: 2 pyruvate, 2ATP, 2NADH
- PDC: decarboxylation of pyruvate by PDC which forms acetyl CoA and NADH… acetyl coa transfers 2C to oxaloacetate forming citrate
- Krebs cycle: 2 pyruvate each get 3NADH, 1FADH2, 1GTP
- ETC: NADH, FADH2 pass their electrons to ETC: 2.5ATP/NADH and 1.5ATP/FADH2
4
Q
Glycolysis overview
A
- Location: cytosol
- Sum of products from glucose: 2ATP, 2NADH, 2H+, 2 pyruvate
- Steps with hexokinase, PFK, and pyruvate kinase are all irreversible
- Always starts with glucose
5
Q
Glycolysis steps
A
- Glucose -> G6P via hexokinase (use ATP: irreversible)
- G6P <-> F6P via phosphohexose isomerase
- F6P -> F1,6BP via PFK-1 (use ATP: Irreversible: rate limiting step)
- F1, 6BP <-> DHAP + G3P cleaved via aldolase
- DHAP <-> G3P via triose phosphate isomerase
- G3P<-> 1, 3BPG via G3P dehydrogenase (generates NADH, H+)
- 1,3BPG <-> 3PG via phosphoglycerate kinase (generates ATP)
- 3PG <-> 2PG via phosphoglycerate mutase
- 2PG <-> PEP via enolase
- PEP -> Pyruvate via pyruvate kinase (generates ATP: Irreversible)
6
Q
Glycolysis regulation
A
- 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 - Low glycolysis: high ATP inhibits PFK which leads to high G6P (F6P and G6P in high equilibrium) to inhibit hexokinase as negative feedback
7
Q
Fermentation
A
- Yeast: Pyruvate from glycolysis -> acetylaldehyde + CO2 (via pyruvate decarboxylase) -> ethanol + NAD+ (via alcohol dehydrogenase)
- Animals: Pyruvate from glycolysis -> lactate + NAD+ (via lactate dehydrogenase)
- Main purpose of fermentation is to regenerate NAD+ to enter glycolysis again to get more ATP
8
Q
Gluconeogenesis overview
A
- Main substrates: pyruvate, lactate, glycerol, glucogenic amino acids (any 3 carbon, non hexose precursors)
- Active when fasting (high glucagon, low glucose)
9
Q
Gluconeogenesis steps
A
- Bypass 1: pyruvate ->oxaloacetate (via pyruvate carboxylase) goes into cytoplasm ->PEP (via PEPCK)
1a. PEP->2PG->3PG->1,3BP->G3P->DHAP->F1,6BP - Bypass 2: F1,6BP -> F6P (via fructose 1,6 bisphosphatase)
2a. F6P->G6P - Bypass 3: G6P to glucose (via glucose 6 phosphatase)
10
Q
Gluconeogenesis /glucose regulation:
A
- Glycolysis occurs when: high F2,6BP, AMP, F1,6BP
- Gluconeogenesis occurs when: high citrate, acetyl coa
11
Q
Glycogenolysis
A
- Irreversible Breakdown of glycogen one glucose residue at a time to glucose 1 phosphate via glycogen phosphorylase (G1P)
- 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
12
Q
Regulation of glycogenolysis
A
- Liver: glycogen phosphorylase is active when low glucose (high glucagon and epinephrine)
- Muscle: epinephrine and Ca2+ activate PK which activates glycogen phosphorylase which activates glycogenolysis in muscle…. (When active=low glucose level=more glycogenolysis)
13
Q
Glycogenesis process
A
- When high insulin (from beta pancreatic)=Addition of glucose to non reducing end of glycogen =storage of glucose
- Process
2a. G6P->G1P via phosphoglucomutase
2b. G1P -> UDP-glucose via UDP glucose pyrophosphorylase
2c. UDP glucose -> glycogen via glycogen synthase
14
Q
Lactic acid cycle (Cori cycle) in Fermentation
A
- 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
15
Q
Pentose phosphate pathway (PPP) functions
A
- 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 - Ribose 5 phosphate synthesis for production of nucleotides
16
Q
PPP stages: in cytosol
A
- Oxidative phase: irreversible (produces 2 NADPH)
1a. G6P ->->ribulose 5 phosphate + CO2 +2NADPH - 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)
17
Q
Shuttles to get NADH through the mitochondrial matrix
A
- 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
- Glycerol phosphate shuttle (muscle, brain): DHAP -> NADH+ + Gro3P -> DHAP + FADH2
18
Q
Aerobic respiration: PDH complex
A
- Pyruvate goes from cytosol (glycolysis) into matrix
- 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 - PDH active: insulin which dephophoylates (phosphatase) PDH to activate it, high pyruvate, high ADP
19
Q
Krebs cycle
A
- Acetyl coa + Oxaloacetate -> citrate (via citrate synthase)
- Citrate -> isocitrate (via aconitase)
- Isocitrate -> alpha ketoglutarate, CO2, NADH (via isocitrate dehydrogenase)
- Alpha keto glutarate -> succinyl coa, CO2, NADH (via alpha ketoglutarate dehydrogenase)
- Succinyl coa -> succinate, GTP (via succinyl coa synthetase)
- Succinate-> fumarate, FADH2 (succinate dehydrogenase)
- Fumarate -> malate (fumerase)
- Malate ->oxaloacetate, NADH (malate dehydrogenase)
20
Q
Anaplerotic sequence
A
- The need to replace oxaloacetate is done via pyruvate being able to become oxaloacetate via pyruvate carboxylase
21
Q
ETC
A
- 4 integral proteins and 2 electron carrier molecules (coenzyme Q (hydrophobic) and cytochrome c (water soluble) in inner membrane
- 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 - H+ from NADH, FADH2 create proton motive gradient in the intermembrane space which powers ATP synthase to generate ATP (3H+=1ATP) in oxidative phosphorylation
- 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)
22
Q
ATP synthase
A
- Proton motive force from inter membrane space push H+ into F0 which spins the F1 allowing it to generate 1ATP/3H+
23
Q
Oxidative phosphorylation energy
A
- 2.5 ATP/NADH ; 1.5 ATP/FADH2
- Whole process generates 36ATP
2a. Glycolysis 6ATP, PDH 6ATP, Krebs cycle 24ATP
24
Q
Fatty acid catabolism/ beta oxidation: mitochondria and peroxisomes
A
- Fatty acid activation: fatty acid + CoA-SH + ATP->formation of acyl CoA via acyl coa synthase (ACS)
- 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 - 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
25
Q
Fatty acid synthesis
A
- Exportation:
1a. Acetyl coa (matrix) + oxaloacetate -> citrate
1b. Citrate -> acetyl coa + oxaloacetate in cytosol - Acetyl coa + co2 -> malonyl coa (ACC)
- Malonyl coa + acetyl coa —-> palmitic acid (16C)
26
Q
Ketogenesis
A
- Occurs in low blood sugar (fasting) or diabetes in liver: low insulin
- Acetyl coa made from (FAS, or glycolysis etc) gets made into ketone bodies: acetoacetate, acetone, D-B-hydroxybutyrate
- These ketone bodies then travel to other cells so they can break them down for energy
27
Q
Amino acid degradation
A
- As a last resort we break down proteins into amino acids which can feed into the citric acid cycle at various time points