Central Metabolic Pathways Flashcards
common routes to breakdown glucose to pyruvate
glycolysis
pentose phosphate pathway
entner-doudoroff pathway (bacteria only)
glycolytic pathway occurs in
cytoplasmic matrix of both pro and eucaryotes
enzymes in glycolysis:
Hexokinase: Note in bacteria that hexose kinase is often replaced by the phosphotransferase system in which the phosphate is supplied by PEP. Isomerase Phosphofructokinase Fructose 1,6-bisphosphate aldolase Triose Phosphate Isomerase Triose Phosphate Dehydrogenase Phosphoglycerate Kinase Mutase Enolase Pyruvate kinase
Summary of Glycolysis
glucose + 2ADP + 2Pi + 2NAD+
2 pyruvate + 2ATP + 2NADH + 2H+
the glycolysis pathway can only be reversed from
PEP to fructose 1,6 bisphosphate
phosphofructokinase is replaced by
fructose 1,6 bisphosphatase (in reverse glycolysis)
ADP allosterically positively regulates
phosphofructokinase
PEP feeds back to negatively regulate
phosphofructokinase
pyruvate kinase is positively regulated by
fructose 1,6 bisphosphate
AMP allosterically negatively regulates
fructose 1,6 bisphosphate phosphatase
fate of NADH
respiration
fermentation
hydrogenase (anaerobic)
Pyrococcus furiosus (Archaea-hyperthermophile) has a modified EMP
ferments carbohydrates and peptides to acetate. does not support growth for monosaccharides. maltose. sulfur as an electron sink
how pyrococcus furiosus differs in EMB (glycolysis)
1]ADP donates phosphate rather than ATP
2]Glyceraldehyde 3 PO4 is oxidized by glyceraldehyde 3 PO4 ferredoxin oxidoreductase (GAPOR) rather than triose phosphate reductase
3]1,3 phosphoglycerate is not produced and therefore the subsequent atp cannot be formed
4[Pyruvate is oxidized by pyruvate:ferredoxin oxidoreductase rather than pyruvate dehydrogenase (sec 7.3.2) to Acetyl CoA and CO2.
5] Instead of producing a reduced NADH, ferredoxin is reduced and linked to a ferre-NADP+ linked enzyme (ferredoxin NADP oxidoreductase or FNOR). The electrons are then given up to form Hydrogen gas
6} ATP is formed when Acetyl CoA is converted to acetate using acetyl CoA synthetase.
Pentose Phosphate Pathway
also called hexose monophosphate pathway
can operate at same time as glycolytic or Entner-Doudoroff pathways
can operate aerobically or anaerobically
an amphibolic pathway
three stages of PPP
1) oxidative decarboxylation
2) isomerization
3) Sugar rearrangement
oxidative decarboxylation
Steps 1-3
1) glucose-6-phosphate dehydrogenase, 2)Lactonase, 3) 6-Phosphogluconate dehydrogenase
The third step produces the decarboxylation.
Two NADPH’s are produced
isomerization
Steps 4-5
Ribulose-5-P is converted to xyulose-5-P and to ribose-5-P
(nucleotide precursor)
xylulose 5 - P to ribulose 5- P to ribose 5 P
sugar rearrangement
Steps 6-8
Ketolase,Aldolase, Ketolase
Ketolase is a two carbon transfer
Aldolase is a three carbon transfer
Important sugars are produced such as erythrose for aromatic amino acid synthesis
Glceraldehyde 3 phosphate can enter the second half of glycolysis.
Pentose Phosphate Pathway
glucose-6-P + 12NADP+ + 7H2O
6CO2 + 12NADPH + 12H+ Pi
Thiobacillus novellas and Brucella abortus does not have a complete EMP or Entner-Doudoroff pathway.
They use Pentose Phosphate pathway and the second half of EMP.
The Entner-Doudoroff Pathway
Similar to PPP but differs after 6-P-gluconate producing 2-keto-3-deoxy-6-P-gluconate (KDPG) (instead of the oxidative decarboxylation.
KDPG is split into pyruvate and glyceraldehydes-3-P.
Only a net of 1 ATP is produced (along with a NADH and a NADPH).
role of ED pathway
This is low yield is justified by its niche.
When E. coli is grown on gluconate, three enzymes are induced:
Glucokinase, 6-P-gluconate dehydratase and KDGP aldolase.
The enzymes
The adavantage to the Entner-Doudoroff Pathway is the use of aldonic sugars such as gluconate.
yield per glucose molecule in ED
1 atp
1 nadph
1 nadh
step 1 of ed
hexose kinase
Glycolysis pathway, Pentose Phosphate pathway and Entner-Doudoroff pathway share the same route from
Glyceraldehyde-3 Phosphate to Pyruvate.
The products are 2 ATP’s, 1 NADH and Pyruvate
Pyruvate Dehydrogenase (The Transition Step
Converts Pyruvate to Acetyl-CoA
enzyme complex in Pyruvate dehydrogenase
TPP, NAD+, FAD, lipoic acid, CoA
Pyruvate dehydrogenase allosterically regulated:
Negatively by NADH and Acetyl CoA
Positively by PEP and AMP
AMP is an indication of low ATP
NADH accumulation indicates respiration is slowing
irreversible steps in TCA
citrate synthase and alpha ketoglutarate dehydrogenase
only membrane bound enzyme in TCA
succiny dehyrogenase
in Gram negative,citrate synthase inhibited by
NADH and alpha ketoglutarate
in Gram positive, citrate synthase inhibited by
ATP
C-1 metabolism lacks
the -ketoglutarate dehydrogenase enzyme.C-1 metabolism instead shows a reductive pathway.
TCA in anaerobes require
sulfur or thiosulfate as terminal electron acceptor
if sugars are catabolized then waht is used to replenish OAA
pyruvate or PEP
TCA enzymes
Citrate synthase (1) Aconitase (2 & 3) Isocitrate dehygrogenase (4 & 5) -ketoglutarate dehydrogenase (6) Succinate thiokinase (7) Succinate dehydrogenase (8) Fumarase (9) Malate dehydrogenase (10) Note the numbering is different on the reductive TCA diagram
bacterium will either have (to replenish OAA)
pyruvate carboxylase or PEP carboxylase(not in animals or fungi)
PEP is positively regulated by __________ and negatively regulated by ________
acetyl CoA
aspartate
reductive TCA lacks
alpha ketoglutarate dehydrogenase and substitutes fumarate reductase for succinate dehydrogenase
Reductive TCA
Succinate thiokinase (6)
Fumarate Reductase instead of Succinate dehydrogenase (7)
Fumarase (8)
Malate dehydrogenase (9)
PEP Carboxylase (10) or pyruvate carboxylase (11) to replace OAA for step 1.
Uses (1) FADH2 and (1) NADH
glyoxylate cycle purpose
aerobic bacteria growing on fatty acids or acetate. (catabolism of fatty acids produces acetyl CoA
It is similar to TCA but lacks the decarboxylations.
Instead uses two (2-C) acetyl CoA’s to make (4-C) succinate. This is the value of the pathway, it is a source of carbohydrate (succinate) derived from acetyl CoA metabolism (lipid metabolism)
Glyoxylate is a key 2-C intermediate.
Two key enzymes of glyoxylate cycle
isocitrate lyase and malate synthase. the end result is succinate and 1 NADH
pyruvate to pep (prokaryotic)
pep sythase or pyruvate phosphate dikinase
pyruvate from malate
Malic enzyme is found in mitochondria and bacteria
It is important if TCA intermediates are used for growth (i.e., Glycolysis is not active and for example bacteria are growing on succinate as a carbon source) and only uses PEP carboxykinase (and therefore needs pyruvate as an intermediate for biosynthesis)
There are two forms one that uses NADH and one that uses NADPH
Malate + NAD+ pyruvate + NADH + CO2
