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Bch301: Metabolism of Carbohydrates
Bch301: Metabolism of Carbohydrates
•The first 5 reactions of the pathway constitute the preparatory phase, where 2
molecules of ATP are invested to convert glucose to fructose 1,6-bisphosphate.
•The bond between C-3 and C-4 of the fructose 1,6-bisphosphate is then
broken to form 2 molecules of glyceraldehyde 3-phosphate.
•The last 5 reactions of the pathway constitute the payoff phase, where each
of the 2 molecules of the glyceraldehyde 3-phosphate derived from glucose is
oxidized to pyruvate.
•Thus, 4 ATP are produced for a molecule of glucose oxidized to pyruvate under
aerobic condition.
•When the 2 ATP used up in the preparatory phase are deducted, the net ATP
produced by the glycolytic pathway under aerobic condition is 2.
•The overall equation for the glycolytic pathway under aerobic condition is:
•The activity of PFK-1 is increased whenever the cellular ATP level is depleted
or when ADP and AMP (ATP breakdown products) are in excess.
•Of the 2 triose phosphates formed in the 4th reaction, only glyceraldehyde 3-
phosphate, can be directly degraded in the subsequent steps of glycolysis.
•This reaction completes the first (preparatory) phase of glycolysis, with each
glucose that passes through being converted to 2 molecules of glyceraldehyde-
3-phosphate.
Reactions of The Second (Payoff) Phase of Glycolysis
•The pyruvate formed first appears in its enol form, then tautomerizes rapidly
and non-enzymatically to its keto form, which predominates at pH 7.
•Glycogen in animal tissues and starch in plants can be mobilized for use within
the same cell by a phosphorolytic reaction catalyzed by glycogen
phosphorylase and starch phosphorylase, respectively.
•This phosphorolytic cleavage occurs on the (1→4) glycosidic linkage that joins
the last two glucose residues at a non-reducing end, generating glucose 1-
phosphate and a polymer one glucose unit shorter .
•The D-hexoses, including fructose, galactose and mannose, can enter the
glycolytic pathway, after being phosphorylated to either glucose 6-phosphate
or fructose 6-phosphate.
Fig. Entry of glycogen, starch, disaccharides & hexoses into the preparatory
phase of glycolysis
METABOLIC FATE OF PYRUVATE UNDER AEROBIC & UNDER ANAEROBIC
CONDITIONS
•The acetyl-CoA enters the citric acid (TCA) cycle and is oxidized to CO2 and
H2O.
•The reactions of the pentose phosphate pathway occur in the cytosol in two
phases.
•The first phase of the pentose phosphate pathway comprises two oxidative
reactions that convert glucose 6-phosphate to ribulose 5-phosphate and
reduce NADP to NADPH.
•The TCA cycle, discovered by Hans Krebs in 1937, is also known as citric acid
cycle or Krebs cycle.
•Fatty acids and amino acids are also oxidized to CO2 via the TCA cycle.
•In the process, metabolic energy is captured in the form of electron carriers
(NADH and FADH2)
•The TCA cycle has eight steps as shown in the next slide.
Fig. The TCA Cycle
AMPHIBOLIC NATURE OF THE TCA CYCLE
Examples:
•The overall rate of the TCA cycle is regulated by the rate of conversion of
pyruvate to acetyl-CoA, catalyzed by pyruvate dehydrogenase (PDH) complex,
and by the reactions catalyzed by citrate synthase, isocitrate dehydrogenase,
and α-ketoglutarate dehydrogenase.
•The production of acetyl-CoA for the citric acid cycle by the PDH complex is
allosterically inhibited by metabolites that indicate a sufficiency of metabolic
energy (ATP, acetyl-CoA, NADH, and fatty acids) and stimulated by metabolites
that indicate a reduced energy supply (AMP, NAD+, CoA).
•On the other hand, succinyl-CoA is an intra-cycle regulator that inhibits citrate
synthase and α-ketoglutarate dehydrogenase.
THE GLYOXYLATE CYCLE
•The glyoxylate cycle is used by plants, yeast, and many bacteria to convert
acetyl-CoA to oxaloacetate.
•Thus, these organisms can use fatty acids as the starting material for glucose
synthesis (gluconeogenesis).
•In plants and many invertebrates, the glyoxylate cycle serves as a mechanism
for converting acetate to carbohydrate.
Note that:
•Each turn of the glyoxylate cycle uses up two molecules of acetyl-CoA and
produces one molecule of succinate, which is then available for biosynthetic
purposes.
•The glyoxylate cycle bypasses the two oxidative decarboxylation steps of the
citric acid cycle, making possible the net formation of succinate, oxaloacetate,
and other cycle intermediates from acetyl-CoA.
•The two oxidative decarboxylation steps of the citric acid bypassed are the
oxidation of isocitrate to α-ketoglutarate by isocitrate dehydrogenase, and
oxidation of α-Ketoglutarate to succinyl-CoA by α-ketoglutarate dehydrogenase
complex.
Fig. The Glyoxylate cycle