MB 414 L14 central carbon metabolism

gluconeogenesis

producing glucose

1. necessary for growing amino acids or lipids

2. usually starts with Glyceraldehyde-3-phosphate (GAP)

3. Has different enzymes for irreversible steps

guest lecture: porphyromonas gingivalis

• Diverse environments alter P. gingibalis metabolism and phenotypic traits (nutritional plasticity)

• beyond amino and nucleic acids, carbon substrates like pyruvate increase its metabolic capabilities

• pyruvate alone cannot sustain growth, but combined with bovine serum albukin (BSA) it significantly increases biomass

Glycolysis (overview)

1. starts with glucose

2. products: 2 pyruvate, 2 NADH, and 2 ATP per glucose

guest lecture: Delftia acidovorans

• malonic acid (TCA cycle inhibitor) supresses both ROS production and growth inhibition

  • toxicity driven by TCA cycle

Glycolysis irreversible reactions (3)

1. glucose→ glucose-6-phosphate

   1. enzyme:hexokinase

2. Fructose-6-phosphate→fructose-1,6-biphosphate

   1. enzyme: phosphofructokinase-1

3. Phosphoenolpyruvate→pyruvate

   1. enzyme: pyruvate kinase

TCA cycle overview

1. starts with pyruvate

2. products:3 CO2, 12 NADH, 3 FADH2, and 3 GTP per pyruvate

TCA carbons

1. starts with 6 at citrate

2. goes down to 5 at a-ketoglutarate

3. goes down to 4 at succinyl-CoA

anaerobic TCA

TCA cycle moves backwards but skips 2 steps involving succinyl-CoA

Pentose phosphate cycle

1. is an alternative to the TCA cycle

2. can fully oxidize glucose through 6 cycles

3. reducing power is in the form of NADPH

4. produces amino acid precursors

   1. not preferred method

Pentose phosphate cycle (final reaction)

1. reactants: glucose-6-phosphate and 12 NADPH

2. products: 6 CO2, 12 NADPH, 12 H+, and phosphate

   1. 1CO2 per cycle

Amino acid families and precursors

1. glutamate family → 2-oxoglutarate [a-ketoglutarate]

2. aspartate family→ oxaloacetate

3. pyruvate family → pyruvate

4. serine-glycine family → 3-phosphoglycerate

5. aromatic family → erythrose-4-phosphate [phosphoenolpyruvate]

6. histidine → ribose-5-phosphate

Precursor location

1. glutamate family:TCA cycle

2. aspartate family: TCA cycle

3. Pyruvate family: glycolysis

4. serine-glycine family: glycolysis

5. aromatic family: pentose phophate cycle

6. histidine: pentose phosphate cycle

glutamate family aa

1. glutamine

2. proline

3. arginine

aspartate family aa

1. aspargine

2. methionine

3. threonine→isoleucine

4. lysine

pyruvate family aa

1. valine

2. alanine

3. leucine

serine-glycine aa

1. serine

2. cysteine

3. glycine

aromatic family aa

1. phenylalanine→tyrosine

2. tyrosine

3. tryptophan

amino acid nitrogen

always comes from glutamate

lipid metabolism overview

1. occurs thorugh b-oxidation

2. catabolizes 2-carbons at a time

3. needs 1 atp per fatty acids tail (regardless of length)

4. primes fatty acids with CoA (only happens once)

b-oxidation products

each product produces 1 FADH, 1 NADH, and 1 acetyl-coA

acetyl-coA from b- oxidation

Each time an acetyl-coa is produced from one cycle of b-oxidation, it can directly be put into the TCA cycle

glyoxylate cycle/shunt overview

1. eliminates the CO2 releaseing steps of TCA cycle

2. important in production of amino acids

3. fixed carbon increases by 2 with each acetate

glyoxylate shunt final reaction

2 acetyl-coA→oxaloacetate

fatty acid synthesis

1. reverse of glyoxylate shunt

2. cost 2-C→1 ATP and 2 NADPH

3. made from acetyl-coA

Guest lecture: alcanivorax borkumensis

• degrades hydrocarbons

• different carbon sources can influence the proteins that are expressed during metabolism

• uses TCA cycle for metabolism but can favor glyoxylate bypass based on the carbon sources

• when hexadecane was the energy source, glyoxylate bypass enzyme expression increased. TCA genes were downregulated

• the different pathways can help conserve carbon and degrade oil efficiently

nucleic acid origin

come from either

1. aspartate

2. glycine

3. ribose