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Structure, Catalysis, and Metabolism in Biological Systems

This document provides an overview and schedule for the second half of the course BioC4331 Structure, Catalysis, and Metabolism in Biological Systems. It outlines the key topics to be covered including carbohydrate metabolism, lipid and amino acid metabolism, and special topics like diabetes and cancer metabolism. The instructor's contact information is provided. Active learning approaches like group discussions and exercises will be used. Assigned problem sets, quizzes, and exams with a partial credit grading policy are also mentioned.

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33 views28 pages

Structure, Catalysis, and Metabolism in Biological Systems

This document provides an overview and schedule for the second half of the course BioC4331 Structure, Catalysis, and Metabolism in Biological Systems. It outlines the key topics to be covered including carbohydrate metabolism, lipid and amino acid metabolism, and special topics like diabetes and cancer metabolism. The instructor's contact information is provided. Active learning approaches like group discussions and exercises will be used. Assigned problem sets, quizzes, and exams with a partial credit grading policy are also mentioned.

Uploaded by

John
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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The second half of BioC4331

Structure, Catalysis, and Metabolism in Biological Systems

Dr. Yue Chen


Associate Professor
Biochemistry, Molecular Biology & Biophysics

7-114 MCB, Minneapolis Campus

E-mail: [email protected]

Phone: 612-626-3340

Office hours: Monday 1:30 pm to 3pm and Wednesday 1:30 pm


to 2:30 pm (when lecturing) or by appointment
So, what are we going to learn –

 How our body digests carbohydrate and turns them into energy

 Why eating too much sugar will make us fat

 What is trans-fat and why we should avoid them

 Why do we have to pee

 What is the cause of diabetes and associated complications

 How does dysregulated body metabolism link to the increased


severity of COVID-19 in patients
Phase I: Carbohydrate metabolism

- Carbohydrate structure
- Glycolysis
- Electron transport chain (oxidative phosphorylation)
- Gluconeogenesis

Phase II: Lipid and amino acid metabolism

- Lipid structure
- Lipid catabolism
- Lipid biosynthesis
- Cholesterol metabolism
- Amino acid catabolism

Phase III: Special topics on metabolism

- Diabetes
- Cancer metabolism
 Active learning in BIOC4331

o Practice drawing structures with a pen and a piece of paper

o Group-based discussions in class (virtually, the link to In-


class Exercises is listed under Chen Course Material)

 Study group discussions and exercises

o Group exercises will be posted on Thu each week (starting


from THIS WEEK, except for the week with Exam 3).

 Assigned Problem Sets, Quizzes, Exams and Grading Policy -


Partial Points

 Good Practice – Reading before class

o Study guide (previously for exams) is updated online each


week before lectures

o Be prepared to memorize!!
Introduction to Metabolism

Review Chapter 13
CATABOLISM: breaks down food for energy and building blocks

ANABOLISM: uses energy and building block to make the molecules we need
Overview of metabolism: 3 types of pathways

Key compounds: glucose, acetate, acetyl CoA, pyruvate, oxaloacetate.


Basic Concepts of Metabolism
• Sun (Energy) + CO2 + H2O  (C6H12O6)n
• Homework: some living cells do not rely on sunlight:
how do they get energy?
• Reduced carbon (in carbohydrates, fats, or proteins) + O2
 CO2 + H2O + Energy
• Polymers are broken down in the intestine. Only
monomers are absorbed.
• Individual biomolecules are broken down by unique
pathways into universal molecules (acetyl-CoA) that can
“feed into” a common energy producing pathway called
the TCA cycle.
Characteristics of Metabolic Pathways

1. Individual metabolic pathways are irreversible.


2. Catabolic and anabolic pathways must differ.
- This allows independent control of the two processes
3. Every metabolic pathway has an early committed step .
4. All metabolic pathways are regulated.
5. Metabolic pathways in eukaryotic cells occur in specific
cellular locations
a. glycolysis in cytosol
b. citric acid cycle in mitochondria
Energy and Biochemical Reactions

• Biologic reactions follow thermodynamic laws.


• Spontaneous reactions release free energy, which is
available to do work. DG = DH – TDS
• Favorable reactions are exergonic and release free energy,
represented by a negative DG.
• Endergonic: Nonspontaneous reactions that absorb free
energy and has a positive DG.
• The free energy change switches sign but keeps the same
magnitude for the reverse of a reaction.
• Enzymes increase reaction rate but do not affect ∆G.
ΔG = change in free energy, for a chemical reaction
depends on [reactants] and [products]

If Rxn = aA + bB cC + dD

[C]c[D]d
ΔG = ΔG’° + RT ln
[A]a[B]b
ΔG’° = free energy change of reaction when all of its reactants and
products are in their standard states (25oC, 1 atmosphere pressure and
unit activities (1 M) of reactants and products). This never happens in
biology. R = Gas constant. pH is 7.

When ΔG = 0,
[C]c[D]d
ΔG’° = -RT ln K’eq K’eq = [A]a[B]b
Effect of metabolite concentrations on ΔG

If Rxn = aA + bB cC + dD

[C]c[D]d
ΔG = ΔG’° + RT ln
[A]a[B]b

A reaction with a positive ΔG’o can move in the forward direction if


the ΔG is negative.
To make the second term in the equation negative, make the
concentration of the products lower than the concentration of the
reactants e.g. ln of anything < 1 is negative.
This happens when products are quickly removed from the reaction by
rapidly using them in a sequential reaction.
How to make the following reaction happen:

Malate + NAD+ <----> oxaloacetate + NADH


If Rxn = aA + bB cC + dD
[C]c[D]d
ΔG = ΔG’° + RT ln = ΔG’° + RT ln Q
[A] [B]
a b

29.7 kJ/mol + (8.3 J/oK·mol)(310oK) lnQ


29.7 kJ/mol + (2.5kJ/mol) (lnQ)
29.7 kJ/mol + (2.5kJ/mol) ln (5)(5)
(10)(10)

-3.5 kJ/mol

Calculate ΔG of the reaction when we reduce the concentration of


oxaloacetate by 50,000 fold
The structures of ATP, ADP, AMP, and adenosine.
Why is ∆G of ATP
hydrolysis so negative?
Question:

What is the weight of the total ATPs that can be generated after
our body digests ONE piece of bread?

We know –
The weight of a piece of bread is 38 g;
Let’s say the bread is completely made of glucose;
Metabolizing one glucose can generate 32 ATPs.
Find out other relevant information you need online.
Coupled Reactions

A thermodynamically unfavorable reaction (positive


G) can be made to occur if coupled with a
thermodynamically favorable reaction (negative G).
Coupled reactions involve shared intermediates.
Oxidation and Reduction Reactions

• The flow of electrons in redox reactions is responsible directly or


indirectly for all cellular work.
• Electrons move from electron rich molecules (food) to metabolic
intermediates to electron carriers to oxygen.
• Oxidation can be loss of electrons, loss of hydrogen, or gain of
oxygen.
• Reduction can be gain of electrons, gain of hydrogen, or loss of
oxygen.
• Oxidation and reduction occur together.
• Transfer of electrons to O2 is exergonic because O2 has ______
standard reduction potential.
Oxidation States of Carbon in Biomolecules

General rule: more C-O bonds or less C-H bonds means


more oxidized !
Learn to spot reactions in which carbon gets oxidized

When carbon gets oxidized, something else must get reduced


Coenzyme
A low molecular weight organic compound, which in
cooperation with an enzyme, facilitates catalysis of a
reaction.

The coenzyme may appear to be a substrate and/or


product. Many coenzymes have a part of their
structure that is derived from a vitamin.

The vitamin is a nutritional requirement since the


organism is unable to biosynthesize an adequate
amount for its own use.

Example: niacin (vitamin B3), is a part of NAD+.


NADH and NADPH

NAD+ is reduced to NADH during many oxidative


reactions of catabolism.

NAD+ collects electrons released during catabolism.

NADH is a form of stored chemical energy: it can


be oxidized in aerobic cells, this oxidation provides
the energy for ADP + Pi --> ATP.

NADPH is also a stored form of reducing power, it


is used to drive the reductive biosynthetic reactions
of anabolic pathways.
The truth about hydrogen, electrons and protons . . .
H = e- + H+
• A hydrogen ion is a proton
• Water dissociates to H+ + OH-, so there are always lots
of protons around free in the cell.
• Protons can exist free in the cell (recall pH), but
electrons can’t.
• To move electrons, the cell uses electron carriers
like NADH and FADH2

In this part of the course we will use the terms proton


and hydrogen ion interchangeably and use short-hand
notations for molecules and reactions. We won’t pay
attention to where the protons came from or go to.

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