Welcome to MBB321 - Metabolism

You are expected to come

into this course with a
relevant solid knowledge
base from MBB222 (and a
bit from MBB231) as well
as some basic organic
chemistry
 MBB321 - introduction
You are expected to come into this course with a relevant solid knowledge base
from MBB222 (and a bit from MBB231) and some basic organic chemistry
With respect to textbook questions- note that the questions are numbered from Edition 7(E7)

This means that at a minimum you need to do the following:

• Read chapter 1 in Lehningher and answer the following questions from
chapter 1: 4a,6,7,8,10,11,12

• Review chapters 2,3,4, and 5 and be able to answer the following

questions in these chapters for the purposes of your first exam:
note that these questions were chosen because of their relevance to MBB321.
chapter 2: 1, 2, 3, 16, 17
chapter 3: 10
chapter 4: 5, 9, 11
chapter 5: no specific question but you should still read the chapter and focus
on protein-ligand interactions
1:1

Note that while the (abbreviated) answers to these questions are found at the back of your text book- the
way to succeed in this course is to try to work them out yourself first and also to understand the answers
 Biochemistry: the chemical
processes of living matter

Metabolism: The entire set of

enzyme-catalyzed
transformation of organic
molecules in living cells; the
sum of anabolism and
catabolism = 13,543

Metabolite: A chemical
intermediate in the enzyme-
catalyzed reactions of
metabolism = 4,140
(12,890 protein structures)

Metabolome: the complete

set of metabolites present
under specific conditions
Brunk et al., "Recon3D enables a three-dimensional view
of gene variation in human metabolism, Nature
Biotechnology (2018); doi:10.1038/nbt.4072 1:2
 Metabolism - why bother? read this article
http://www.nytimes.com/2016/05/15/magazine/warburg-effect-
an-old-idea-revived-starve-cancer-to-death.html?_r=0

“Scientists now wonder if metabolism could prove to be the long-sought “Achilles’ heel” of
cancer, a common weak point in a disease that manifests itself in so many different forms.”

Based on 2010 estimates:

• 2 out of 5 Canadians (45% of
men and 42% of women) are
expected to develop cancer
during their lifetimes.

• 1 out of 4 Canadians (29% of

men and 24% of women) is
expected to die from cancer.

“There are typically many mutations in a single cancer. But there are a limited number of ways
that the body can produce energy and support rapid growth. Cancer cells rely on these fuels in a
way that healthy cells don’t. The hope of scientists at the forefront of the Warburg revival is that
they will be able to slow — or even stop — tumors by disrupting one or more of the many
chemical reactions a cell uses to proliferate, and, in the process, starve cancer cells of the
nutrients they desperately need to grow”.
What is the Warburg effect ? 1:3
Warburg effect
In oncology: the high anaerobic use of glucose and production of
lactic acid in tumor cells - even in the presence of oxygen

https://medium.com/@drjasonfung/the-paradox- read more about the

of-cancers-warburg-effect-7fb572364b81 Warburg effect here

more from the NY times article on the previous slide:

“Even James Watson, one of the fathers of molecular biology, is
convinced that targeting metabolism is a more promising
avenue in current cancer research than gene-centered
approaches. At his office at the Cold Spring Harbor Laboratory
in Long Island, Watson, 88, sat beneath one of the original
sketches of the DNA molecule and told me that locating the
genes that cause cancer has been “remarkably unhelpful” — If
he were going into cancer research today, Watson said, he
would study biochemistry rather than molecular biology.”

“I never thought, until about two months ago, I’d ever have to
learn the Krebs cycle,” he said, Now I realize I have to.”

also read this article

http://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(15)00241-8 1:4
Metabolic processes take place inside of cells

schematic diagram of an animal cell plus electron micrographs of organelles 1:5

1:6
The cytoplasm of a cell is crowded

1:7
 morphologically cells
vary in shape and size

cells also vary physiologically

nerve cell
red blood
cells

human
bacteria sperm cells
white blood
cells

platelets

Mouse embryonic
stem cells cancer cells (myeloma)

White blood cell (monocyte)

with bacteria on cell surface
1:8
Cells are differentiated in structure and in function

Live and dead heart

cells (myocytes)
neutrophil macrophage
phagocytosing S.aureus

Dendritic cell
neuron

Human bone
marrow stem cells 1:9
What limits the size of a cell?

Animal and plant cells: 5 to 100 µm (diameter)

Bacterial cells: 1 to 2 µm (length)
Lowest size limited by:
• minimum number of biomolecules required for
existence

Upper size limited by:

• Rate of diffusion of solutes in the aqueous
intracellular environment

if a cell requires oxygen to produce energy the surface

area to intracellular volume must be large enough so
that oxygen can easily diffuse into every part of the cell

What happens when metabolic

processes consume O2 faster
than diffusion can supply it?

1:10
How many cells in an adult human?
 example: Tumor access to Glucose and oxygen

How does oxygen get to cells? How does glucose get to cells?

What happens when tumor growth exceeds blood vessel growth?

Ask yourself how energy is

produced in the presence and
absence of oxygen

1:11
Oxidation states of carbon in biomolecules
(methyl)
•Five oxidation states of carbon
(depending on the elements with which
carbon shares electrons)

•Each compound below is formed by

oxidation (loss of electrons) of the
carbon in the compound above it

•Carbon dioxide is the most highly

oxidized form of carbon found in living
organisms

Oxidation of carbon
in carbon-hydrogen bonds the more electronegative carbon “owns” the two
electrons shared with hydrogen

In carbon-oxygen bonds electron sharing is unequal in favor of oxygen

(oxygen is more electronegative)
1:12
oxidation reactions generally release energy
most living cells obtain the energy
needed for cellular work by
oxidizing metabolic fuels
•the energy yielding (catabolic)
pathways of metabolism are
oxidative reaction sequences
•that result in the transfer of
electrons from fuel molecules
•through a series of electron
carriers and finally to oxygen

1:13