Intro to Metabolism

Question 1

Catabolic pathways

Answer 1

– Break down larger molecules into smaller ones
– General strategy to extract H/e- to be delivered to the electron transport
chain
– Sometimes to make ATP directly (substrate level phosphorylation) –> ATP generating

Question 2

Anabolic pathways

Answer 2

– Build larger molecules from smaller substrates
– Generally requires input of energy (ATP) or reducing power (NADPH, NADH). –> ATP utilising

Question 3

ATP
why we use atp

Answer 3

energy currency
VERY STABLE
adenosine triphosphate

energy is required to do work:
chemical : building big molecules e.g. proteins/fats
transport : require ATP for active transport
mechanical : requires movement

–> Reactions that require free energy can be
coupled to ATP hydrolysis to make them
thermodynamically favourable
(breaks 1 or 2 phosphate groups of ATP to ADP/AMP)

Question 4

kinases

Answer 4

catalyse a phosphorylation reaction
–> phosphorylates proteins, add protein groups

Question 5

phosphatases

Answer 5

catalyse dephosphorylation reactions

–> dephosphorylates someting, removes phosphate groups

Question 6

phosphorylases

Answer 6

– catalyse a phosphorolysis reaction

uses phosphate groups to split molecules apart

Question 7

Synthases vs Synthetases

Answer 7

synthases
– catalyse condensation reactions in which no nucleotide triphosphate is required (no ATP)
synthetases
– catalyse condensation reactions that require a nucleotide triphosphate (needs ATP)

Question 8

Dehydrogenases

Answer 8

Catalyse oxidation-reduction reactions
– Usually involve NAD+ /FAD as cofactors
– Named for the substrate that is oxidised by NAD+ /FAD
– For example:
pyruvate + NADH –> lactate + NAD+
NADH –> NAD+ is an oxidation reaction and pyruvate –> lactate is a reduction reaction so the substrate is lactate and the enzyme is lactate dehydrogenase.

Question 9

FAD

Answer 9

Flavin adenine dinucleotide
picks up 2H+/2e-
CH2CH2 –> C=C

Question 10

NAD+

Answer 10

Nicotinamide adenine
dinucleotide
the reduction of NAD+ because it gains electrons (the “e-“ term in the equation) and a hydrogen ion, leading to a change in charge. The overall result is the conversion of NAD+ to NADH

Question 11

Coenzyme A

Answer 11

can’t diffuse across plasma membrane, can bind to molecules so won’t escape from cell.
–> tagging/ “recognition flag”

Question 12

Strategy of Fuel Oxidation: Stage 1

Answer 12

fats –> fatty acid (beta oxidation)
carbs – glucose (glycolysis)
protein –> aa (20 aa so several pathways)

Rip hydrogens/electrons (H/e -)

fatty acid –> acetate
glucose –> pyruvate –> acetate
aa –> acetate

acetate is 2 carbon (2 C)
CoA binds to form acetyl CoA

Question 13

Strategy of Fuel Oxidation: Phase 2

Answer 13

Rip hydrogens/electrons (H/e -) out of acetate [Acetyl- CoA] (during krebs cycle)
Complete oxidation of carbon atoms to CO2

Question 14

Making ATP with the H+ gradient

Answer 14

The protons flow (under pressure!) through a channel in the inner mitochondrial
membrane
As they come in, they cause another protein to rotate…
… which, in turn, interacts with the subunits of the ATP synthase
… to generate ATP from ADP and phosphate

Question 15

SEVEN BIG Concepts!

Answer 15

1. The H/e- carriers are in short supply
2. ADP is in short supply
3. ATP is really stable
4. The inner mitochondrial membrane is impermeable to protons
5. Protons only flow into the matrix if the ATP is being made
6. The proton pumps don’t work if the proton gradient is very high
7. No proton pumping, no H/e- movement down the ET chain

Question 16

Fuels: Fatty Acids

Answer 16

• Nearly all the carbon atoms are fully reduced
• Stored as triglyceride (1 glyercol molecule + 3 fatty acids with ester bonds)
• Totally hydrophobic
• Very energy dense (37 kJ/g)
• Huge stores (many kg)
• Can’t be used by brain

Question 17

Beta-oxidation

Answer 17

Beta-oxidation
* Fatty acids trapped in cytoplasm as
Fatty Acyl-CoA
* Carnitine acts as carrier and helps transport into mitochondria
* H/e- ripped out by FAD and NAD+ from the fatty acid and it leaves an acetate chunk
* Cycle repeats….

Question 18

Fuels: Glucose

Answer 18

• Reasonably reduced
• Stored as glycogen
• Hydrophilic, lots of water associated
• Inefficient; 16 kJ/g (but only 6 kJ/g wet)
• Low stores (300 g)
• Can be used by all tissues
• Brain has an obligatory requirement!

Question 19

Glucose Oxidation

Answer 19

• Glycolysis
• Every cell in your body, from muscle cells to skin cells, can do glycolysis*
• Takes place in cytoplasm
• No requirement for oxygen
• Very, very fast
• Very, very inefficient
• ATP generation almost irrelevant (with
  some BIG exceptions) compared to
  oxidative phosphorylation
• Pyruvate must be transported into
  mitochondria for full oxidation

Question 20

Fuels - Protein

Answer 20

• Many pathways for amino acid catabolism
• Channel into pyruvate, acetyl-CoA or Krebs
• Energy release about 17kJ/g
• Need to dispose of amine groups
• ‘store’ is about 5-10 kg
• We don’t ‘store’ protein – it all has a function
• Making protein has cost us a LOT of energy so breaking down protein is last resort fuel source