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.
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
- 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
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
- 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
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller miryam_guirguis. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $10.49. You're not tied to anything after your purchase.
