Class notes

Metabolic Biochemistry

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McGill University (Mcgillu)

This is the whole class notes for metabolic biochemistry. Some of the concepts it contains are: Glycolysis, Citric Acid Cycle/Kreb's cycle, Oxidative phosphorylation, Electron transport chain, Ketone bodies, Lipolysis, lipid synthesis, purine & pyrimidine synthesis & more.

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Uploaded on December 15, 2023
Number of pages 63
Written in 2023/2024
Type Class notes
Professor(s) Maxime denis
Contains All classes

metabolic biochemistry
finals
notes for finals
class notes
whole class notes
glycolysis
gluconeogenesis
carbohydrates metabolism
fructose
mannose
galactose
electron transport chain
citric acid cycle
k

Institution McGill University (Mcgillu)
Education Biology
Course Unknown

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BIOC 311

Glycolysis:

Metabolic reactions occur at equilibrium, the whole system is not:
- Irreversible steps
- Basal metabolic rate (always losing energy)

ΔG° => Nature of a reaction (endergonic vs exergonic)
ΔG° > 0, (+) => endergonic (requires energy)
ΔG° < 0, (-) => exergonic (releases energy)

ΔG => reversibility in vivo
ΔG = 0: reaction is at equilibrium => reversible
ΔG < 0, (-): releases energy => irreversible

Glucose Uptake:
- Transport
o Symport uses sodium diffusion to also drive glucose from blood inside (passive
transport – 2ndary active transport)
- Uptake:
o Pancreatic beta-cells
o When [glucose]_blood > 5.5mM => Glucose is released into the blood
o Glut2 glucose channel always present
▪ When [glucose]_blood > 5.5mM glucose diffuses in via glut-2 -> ATP
production -> Potassium channel expelling channel out is inhibited ->
depolarization -> Calcium enters -> insulin (hormone) is released (synapse
style) into the bloodstream
o Insulin – Stimulates glucose uptake in cells
▪ Triggers liver to produce glycogen
▪ Glut4 glucose receptor recruited to cell surface when insulin present

Energy Expenditure:
1. ATP stored in muscles
2. P-Creatine
3. Anaerobic glycolysis
4. Aerobic glycolysis
5. Aerobic lipolysis

Glycolysis:
- Not require O2
- 1 Glucose generates: 2 ATPs, 2 NADH, 2 pyruvates
- Requires a fresh supply of NAD+
o In presence of O2 done via ox-phos
o In absence of O2
▪ Muscle: pyruvate -> lactate

Glucagon: hormone stimulating glycogen breakdown
Glycogen: glucose polysaccharide

,BIOC 311

▪ Yeats & bacteria: pyruvate -> ethanol (fermentation)

- Pathway
1. Glucose -------- Hexokinase or Glucokinase ---------> G-6-P
(glucose phosphorylated once inside cell)
a. Hexokinase:
i. Processes any 6C sugar into G6P (including fructose)
ii. Present in all cells
iii. High affinity
iv. Modulator: G6P
b. Glucokinase (back up enzyme if too much glucose for hexokinase capacity)
i. Processes only glucose
ii. Present only in liver and pancreas
iii. Low affinity
iv. Modulator: Glucokinase regulator protein (GKRP)
• Binding partner to glucokinase that keeps GK in the nucleus when
[glucose]_blood is low
• When glucose levels increase GKRP releases glucokinase to the
cytoplasm where it can produce G6P
v. Stores extra glucose as glycogen
2. G-6-P <-------- phosphoglucose isomerase ---------> F-6-P
a. Directionality depends on abundance
3. F-6-P -------- Phosphofructokinase (PFK1) ---------> FBP (fructose-1,6-bisphosphate)
a. Committing step to glycolysis
b. Activators: AMP; F2,6P
c. Inhibitors: ATP; citrate
d. AMP activation is more potent than ATP inhibition
e. Allosteric regulation
i. Adenylate kinase (ADK) (converts 2 ADP → 1 ATP + AMP)
• During exercise ~ 10% ATP is converted to ADP
• Adenylate kinase converts ADP to back to ATP with AMP
• Keeps ATP abundant for exercise
• Generates AMP to activate (PFK1)
f. Substrate Cycles
• At rest: Equilibrium
• Exercise: F2,6P activates PFK AND inhibits
FBPase
• F2,6P is not an intermediate in glycolysis
1PFK2 converts FBP to F2,6P

FBPase2 converts F2,6P to FBP
g. Covalent modification

Glucagon: hormone stimulating glycogen breakdown
Glycogen: glucose polysaccharide

,BIOC 311

4. Reversible steps
a. FBP <---------Aldolase--------> GAP + DHAP
i. GAP & DHAP are interchanged
ii. GAP is the one that proceeds with glycolysis (2 GAPs/glucose)
b. Last product of reversible is PEP (phosphoenolpyruvate)
5. PEP (High energy intermediate) -------- Pyruvate kinase --------> Pyruvate
a. Activator: F1,6B
b. Inhibitors: ATP, glucagon, cAMP, PKA (through F2,6P)
- 3 committed/irreversible steps to glycolysis
o Hexokinase
o PFK1
o Pyruvate kinase
- ATP & Energy
o Used: 2 ATP
o Made: 4 ATP, 2 NADH (2.5 ATP/NADH)
▪ Net product:
• Aerobic glycolysis (use NADH): 7 ATP
• Anaerobic glycolysis (no NADH used): 2 ATP
- Differential Hormonal regulation of PFK2
o LIVER ISOZYME
▪ Need to supply blood with fresh glucose
▪ When Fasting/prolonged exercise (glucose deprived) => F2,6P decreases
• Glucagon & cAMP increase => PKA is activated
o PKA shuts down kinase activity of PFK2
o Phosphatase activity takes over

o Reaction reverted to regenerate F6P
o HEART ISOZYME
▪ Gluconeogenesis doesn’t happen in the heart
▪ When stress => F2,6P increases
• Epinephrine and cAMP increase => PKA activated
o PKA phosphorylates PFK2 activating its kinase activity
o PKA shuts down phosphatase activity

Glucagon: hormone stimulating glycogen breakdown
Glycogen: glucose polysaccharide

, BIOC 311

- Investment phase: HK, PFK1
- Payoff phase: GAP ------> Pyruvate (2 ATP/GAP converted ∴ 4 ATP/Glucose since 2
GAPs/glucose)

Carbohydrates:

Glucose, Galactose, Fructose => 6C sugars
 Generate 32 ATP via aerobic catabolism

Sucrose (Glucose-Fructose), Lactose (Glucose-Galactose), Maltose (Glucose-Glucose) => 12C
 Generate 64 ATP via aerobic catabolism

Fructose
- Muscle (minor)
o Fructose ----- Hexokinase -----> F6P (glycolysis intermediate)
o F6P ----- PFK -----> Fructose-1,6-phosphate
o Fructose-1,6-phosphate ----- Fructose-1,6-phosphate aldolase -----> GAP+ DHAP
o GAP ➔ ➔ ➔ Glycolysis
- Liver (major)
o Fructose ----- Fructokinase (not regulated) -----> Fructose-1-Phosphate
Fructose-1-phosphate interconverts to its open chain form (equilibrium)
o Fructose-1-Phosphate ----- Fructose-1-phosphate aldolase -----> Glyceraldehyde + DHAP
▪ Option 1
• Glyceraldehyde => GAP ➔ Glycolysis
• DHAP => GAP ➔ Glycolysis
▪ Option 2
• Glyceraldehyde => Glycerol => Glycerol-3-phosphate => DHAP =>
GAP ➔ Glycolysis
o Glycerol-3-phosphate: glycerophospholipid
(triacylglycerol)
- Points of entry into glycolysis
o Muscle: F6P (Before PFK point of control)
o Liver: GAP (After PFK point of control – could contribute to dyslipidemia seen
nowadays)
- Glucose vs Fructose in liver: FED
o In Fed, liver is an anabolic organ => generates glycogen
▪ Anabolic organ: organ that makes/synthesizes larger molecules from
smaller ones
o Glycogen is before PFK control
▪ Glucose ---------> G-6-P --------> G-1-P --------> Glycogen
o Fructose bypasses PFK control, so it will proceed to CAC
▪ If fed & at rest (no ATP generation required (excess ATP) – CAC inhibited),
Fructose will be converted to FA

Glucagon: hormone stimulating glycogen breakdown
Glycogen: glucose polysaccharide

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