Have fun, enjoy, but do NOT sit back

About me Systems microbiologist Interested on evolu>on of Life

How environmental dynamics shape Life Model organisms are mostly Lac>c acid bacteria and cyanobacteria Combine experimental and theore>cal approaches Facilitate applica>ons related to Sustainability and Health Sciences Very limited knowledge of Dutch (my apologies)

Filipe Branco dos Santos

Ac>va>on of Prior Knowledge what you have to bring into this lecture 1st year (Structures of Life) Cell components Cell composi>on This year (Dynamic aspects of Life) Enzyme mechanisms Transport and signaling Catabolism Bioenerge>cs DNA and RNA processing Protein synthesis Here we will focus on: How all processes in a cell are intertwined and regulated Usefulness of models to understand LIFE

Joselyn Vreede

Joost Texeira de MaUos

Paul Franz

Filipe Branco dos Santos

1st lecture Re-cap of cellular metabolism

Metabolism (metabolikos) meaning changeable. Refers to chemical processes occurring within a living cell.

Reac>ons in cells do not work in isola>on Together they form a network => Represented as maps!

Reac>ons in cells do not work in isola>on Together they form a network => Represented as maps!

Complexity can be overwhelming! Models can be used to summarize and help understand Life

What is the most important feature of a model? a. Completeness b. Accuracy c. Usefulness d. other

Reac>ons in cells do not work in isola>on Together they form a network => Represented as maps!

Models (e.g. maps) are a representa>on of reality => INCOMPLETE! Accuracy depends on quality of informa>on used to develop model There is no point in making a model if this is not useful somehow to us (personal view)

Models are useful ONLY if they can help us, so lets simplify

From this

Catabolism Hydrolysis of polymers to amino acids, nucleo>des, monosaccharides and faUy acids. Further degrada>on by oxida>ve reac>on. Energy conserved in ATP and reduced co-enzymes [NAD(P)H] Why do cells need high energy molecules?

Anabolism Large molecules (oden polymers) are synthesized. Fueled by catabolism. Is that so???

Heterotroph u>lize an organic carbon source Autotroph u>lize inorganic sources of essen>al elements How? Chemotrophs oxida>on of inorganic molecules (NH4+, H2, H2S) Phototrophs metabolic energy is generated by (sun)light

Key concept

Reac@on classica@on Anabolic synthesis of biomass components Catabolic synthesis of high energy compounds and reduced co-enzymes Same principle can be used to classify pathways!

How would you classify Acetate kinase?

Acetyl-P + ADP Acetate + ATP

How would you classify Acetate kinase?

Acetyl-P + ADP Acetate + ATP

Catabolic

How would you classify Acetate kinase?

Acetyl-P + ADP Acetate + ATP

Anabolic

How would you classify Glucose transport in a chemoheterotroph?

Glucose (e) => Glucose (c)

a. Catabolic b. Anabolic c. Not sure

How would you classify Glucose transport in a chemoheterotroph?

Glucose (e) => Glucose (c)

Key concept: Amphibolic reac>on

Can you think of an amphibolic pathway?

hUp://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=TCA. Licensed under CC BY-SA 3.0 via Wikimedia Commons

Re-cap

Key concept: Shared metabolism across species Suggests common origin of LIFE!

Standard Gibbs free energy

Actual Gibbs free energy

Ac7va7on of Prior Knowledge back to the basics

Ini>al condi>ons

If G = 0, If G < 0, If G > 0,

If mass ac>on ra>o (Q) Keq => near-equilibrium reac>ons => reversible If mass ac>on ra>o (Q) Keq => metabolically irreversible reac>ons => irreversible

Key concept:

Why are the beakers not the same size? What happens if ?

Key Concept: steady-state

WC_2

How do cells distribute resources amongst dierent func@ons?

How is this regulated?

How is this regulated?

Please read Rossell S et al. (2006) Unraveling the complexity of ux regula>on: a new method demonstrated for nutrient starva>on in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103:216671.

f.brancodossantos@uva.nl Exam level ques>on, preferably mul>ple choice