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FUNGAL METABOLISM AND FUNGAL PRODUCTS 127

• Dihydroxyacetone phosphate (in the Embden–
  Meyerhof pathway) can be converted to glycerol for
  lipid synthesis.


• Acetyl-CoA is used for synthesis of fatty acids and
  sterols.


• α-ketoglutaric acid is used to produce amino acids
  of the important glutamate “family” (glutamate,
  proline, arginine).


• Oxaloacetate is used for the equally important
  aspartate family (aspartate, lysine, methionine,
  threonine, isoleucine).

Therefore, the question arises, how can the pathways

for energy production continue when intermediates

are removed?

The main problem would arise when intermediates

of the TCA cycle are removed, thereby breaking the

cycle. This problem is overcome by special anaplerotic

reactions (literally “filling-up” reactions) which

replenish the missing intermediates. One such reaction

sequence is the glyoxylate cycle, described later in a

different context. Another type of anaplerotic reaction

involves the coupling of CO 2 to pyruvic acid, to give

oxaloacetate, as follows:

The vitamin biotinserves a crucial role as the co-

factor of pyruvate carboxylase, acting as a donor or

acceptor of CO 2. Biotin also is the cofactor in other

carboxylation reactions. This explains why several

fungi need to be supplied with biotin in the growth

medium if a fungus cannot synthesize it (see Table 6.1).

How are sugars generated from nonsugar

substrates?

Sugars are always needed for the synthesis of fungal

walls, nucleic acids, and storage compounds, so how

are they produced when a fungus is growing on non-

sugar substrates? This is done by a process termed

gluconeogenesis(the generation of sugars anew) and

is shown in Fig. 7.5. Many of the steps are simply a

reversal of the Embden–Myerhof pathway, but the

step between phosphoenolpyruvate and pyruvate in this

pathway is irreversibleand so must be bypassed.

Consider the case of a fungus growing on acetate

(2-carbon) as the sole carbon source. After uptake,

acetate is converted to acetyl-CoA and is used to gen-

erate oxaloacetate by the glyoxylate cycle– a short-

circuited form of the TCA cycle. The first reaction step

is the cleavage of isocitrate (a 6-carbon intermediate

of the TCA cycle) to yield succinate (4-carbon) and

glyoxylate (2-carbon). Then glyoxylate is condensed with

CH 3 (CH 2 )nCH 2 CH 2 CH 3 CH 3 (CH 2 )nCH 2 CH 2 COOH

CH 3 (CH 2 )nCH 2 CH 2 CO.S.CoA

n-Alkane Carboxylic acid

CH 3 (CH 2 )n–2CH 2 CH 2 CO.S.CoA + CH 3 CO.S.CoA CH 3 (CH 2 )nC.CH 2 CO.S.CoA

Acetyl-CoA

CoA.SH

CoA.SH

(coenzyme)

Repeat

β-Oxidation

O

Fig. 7.4Outline of the reactions in b-oxidation – a process that occurs in the mitochondria of fungi. Long-chain fatty

acids are activated by combining with coenzyme A and then enter a repeating cycle in which a molecule of acetyl-

coenzyme A is removed in each turn of the cycle. Since most fatty acids have an even number of carbon atoms, this

results in the complete conversion of fatty acids to acetyl-CoA. Long-chain hydrocarbons (n-alkanes; top left) such as

those in aviation kerosene (Chapter 6) can also be processed through this pathway, but first they need to be oxidized

by oxygenaseenzymes, which catalyze the direct incorporation of molecular oxygen into the molecule.

pyruvate + ATP + HCO 3 −

oxaloacetate + ADP + Pi

pyruvate carboxylase