Catabolism Part 1

Catabolism

Breakdown of molecules to release energy and building blocks

Central metabolism

Conserved pathways converting substrates into energy and precursors

CMP

Central metabolic pathways shared among microbes

Heterotroph

Consumes organic substrates for energy and carbon

Conservation

CMPs like glycolysis conserved across life forms

Pathways

EMP, PP, TCA, and ED are main metabolic routes

Glycolysis

EMP pathway for sugar catabolism and energy production

Pentose phosphate

PP pathway producing NADPH and biosynthetic precursors

TCA cycle

Citric acid cycle generating NADH, FADH2, and CO2

Entner-Doudoroff

ED pathway alternative to EMP in many bacteria

Substrates

Carbohydrates, lipids, proteins, nucleic acids, and aromatics

Gustav Embden

Contributed to glycolysis pathway discovery

Otto Meyerhof

Elucidated steps in glycolysis (1930s)

Jakub Parnas

Collaborated on glycolysis research

EMP

Embden-Meyerhof-Parnas pathway for carbohydrate catabolism

Non-glucose sugars

Converted to glucose-6-phosphate for glycolysis

G6P

Glucose-6-phosphate; entry compound into glycolysis

Pyruvate

End product of glycolysis used in TCA cycle

NADH

Energy carrier produced during glycolysis

ATP

Energy molecule produced by substrate-level phosphorylation

Pentose

Five-carbon sugar metabolized in PP pathway

Ribulose-5P

Intermediate in pentose phosphate pathway

NADPH

Energy carrier for biosynthesis and ROS detoxification

ROS

Reactive oxygen species; can damage microbial cells

Detoxification

NADPH neutralizes ROS in microbes

Ru5P

Ribulose-5-phosphate, precursor for nucleotides

Oxidative branch

PP pathway variant for energy generation

Reductive branch

PP pathway variant for biosynthesis

Gluconate

Sugar acid metabolized via ED pathway

GntP

Symporter that imports gluconate into cells

GntK

Kinase phosphorylating gluconate for metabolism

G6PDH

Glucose-6-phosphate dehydrogenase in ED pathway

Pgl

Lactonase enzyme in ED metabolism

PTS

Phosphotransferase system transporting sugars into cells

6PG

6-phosphogluconate metabolized via ED pathway

ED evolution

Entner-Doudoroff predates glycolysis evolutionarily

ED presence

Found in ~25% of named bacterial species

PP presence

Present in bacteria and eukarya; mostly absent in archaea

ED role

Used for sugar metabolism in intestines

Gluconic acid

Substrate commonly catabolized by ED pathway

Bacteria

Often combine EMP, PP, and ED for metabolism

Anabolism link

CMPs provide precursors for biosynthesis

Waste products

Generated alongside energy and precursors

Energy carriers

ATP, NADH, NADPH generated in CMPs

CMPs

Convert substrates into energy, waste, and building blocks

Carbon fate

Transformed into energy, CO2, or biosynthetic precursors

Ligninocellulose

Plant material metabolized using EMP and PP pathways

Ligninocellulose mass

180 billion tons metabolized yearly by microbes

TCA intermediates

Used for biosynthetic reactions in cells

Metabolic conservation

Shared across bacteria, archaea, and eukaryotes

Archaea

Often lack full PP or use ED variants (spED, npED)

Haloferax volcanii

Archaeon with specialized ED pathway

Eukaryotes

Some diatoms and plants have ED enzymes

Rice

Plant example with partial EMP and ED components

Barley

Plant example with partial EMP/ED pathways

Energy conversion

CMPs convert carbon substrates into usable energy

Building blocks

CMPs supply metabolites for anabolism

Carbohydrates

Preferred substrates for microbial catabolism

CAZymes

Carbohydrate-active enzymes hydrolyzing polysaccharides

Aldehyde sugars

Products of glycosidase activity

Alcohol sugars

Intermediate metabolites in carbohydrate catabolism

Acid sugars

Oxidized carbohydrate derivatives

Microbial diversity

Different species use varying CMP entry points

EMP frequency

Occurs in over 90% of named microbes

PP frequency

Occurs in >90% of bacteria and eukarya

ED frequency

Occurs in ~25% of bacterial species

ROS role

Causes structural damage; mitigated by NADPH

Energy storage

CMPs generate ATP for later use

Work energy

ATP fuels cellular processes

Metabolic waste

Byproducts of catabolism

Pyruvate use

Feeds into TCA for further oxidation

CMP goal

Energy production and precursor formation

Metabolic branch

Oxidative vs reductive PP functions

Antimicrobials

None target EMP, ED, or PP pathways

ED discovery

1952; major bacterial sugar metabolism route

EMP discovery

1930s-40s; universal glycolytic pathway

PP discovery

1930s-50s; pathway for pentose metabolism

TCA discovery

1937; citric acid cycle by Krebs

E. coli

Model organism using EMP, PP, and ED pathways

T. sirtalis

Example organism showing metabolic conservation

C. lupis

Microbe with conserved central pathways

Noor et al 2011

Described conservation of microbial catabolism

Fabris 2012

Identified ED-like pathways in plants and diatoms

Rice et al 2000

Described ED variants in Haloferax volcanii

lipids

animal fats, dairy, plant fats, seeds & co.

lipase

specialized hydrolase for assimilation of carbon from fats

Fat metabolism

___ by microbes is used commercially in the (1) food industry, (2) pharmaceuticals, (3) cosmetics, (4) medical diagnostics, and is central to (5) infectious disease

Mycobacterium tuberculosis

(TB) uses fats to survive for decades (aka latency) in its host in tubercle lesions

tubercles

Latent TB hydrolyze stored lipids to glycerol, and fatty acids for food inside lesions

Glycerol

___ is metabolized by glycolysis to pyruvate, ATP and NADH

beta-oxidations

Fatty acids go through a series of ___

acetyl-CoA

products of beta-oxidations

Krebs cycle

acetyl-CoA is further metabolized by ___

protease

hydrolase for proteins to become peptide amino acid

carboxylic acid intermediates

peptides are further deaminated to ___ of CMPs

Kreb’s cycle

carboxylic acid intermediates are further catabolized via ___ ___