Carbohydrate metabolism

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For each of the major pathways of carbohydrate metabolism (glycolysis, Krebs cycle, glycogen metabolism, gluconeogenesis and pentose phosphate pathway) describe its purpose (products), strategy (general means by which the purpose is achieved), stoichiometry and regulation

Glycolysis

Purpose

  • Initial metabolism of glucose and other carbohydrates
  • Catabolic pathway
  • produces ATP

Strategy

  • substrate level phosphorylation
  • oxidation-reduction (redox) reaction which produces NAD

Stoichiometry

  • C6H12O6 (glucose) + 2 NAD+ (niacin derivative) --> 2 CH3-CO-COO- (pyruvate) + 2NADH2+ + 2 ATP + 2 H2O

Regulation

  • allosteric inhibition of the enzyme phosphofructokinase by ATP
  • this is feedback inhibition

Krebs Cycle

Purpose

  • To complete the breakdown of food to produce energy-rich molecules (cellular respiration)

Strategy

Stoichiometry

  • CH3-CO-COO- + 4 NAD+ + FAD + GDP + Pi + 2 H2O --> 2 CO2 + 4 NADH2+ + FADH2 + GTP

Regulation

  • several enzymes of the Krebs cycle are inhibited by ATP and/or NADH2+.

Glycogen Metabolism

Purpose

  • To maintain glucose levels in the blood

Strategy

  • precursor of glycogen synthesis is UDP-glucose
  • glycogen degradation mainly achieved by glycogen phosphorylase

Stoichiometry

Regulation

  • glycogen degradation – glucagon and epinephrine (activate glycogen phosphorylase)
  • glycogen biosynthesis – insulin

Gluconeogenesis

Purpose

  • Produces glucose from non-carbohydrate precursors, such as glycerol and glucogenic amino acids

Strategy

  • Cori cycle
    • fructose -> fructose 6-P -> glucose 6-P -> glucose
    • All except 2 reactions of glycolysis can be reversed. These are avoided in gluconeogenesis

Stoichiometry

  • 2 pyruvate + 4 ATP + 2 GTP + 2 NADH2+ + 6H2O --> glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+

Regulation

Pentose Phosphate pathway

Purpose

  • Alternative pathway for oxidation of glucose

Strategy

  • First part is oxidative: produces 1 mole of CO2 and 2 moles of NADPH2+ per mole of glucose
  • second part is non-oxidative: rearranges products of oxidative reaction so they can enter glycolysis or gluconeogenesis

Stoichiometry

  • maximizing NADPH2+ production: glucose 6-P + 12 NADP + 6H2O --> 6CO2 + 12 NADPH2
  • maximizing ribose production: 5 glucose 6-P --> 6 ribose 5-P

Regulation

  • glucose 6-P dehydrogenase is the committed step.
  • Regulated by availability of NADP+


Describe the biochemical basis of fetal alcohol syndrome and methanol intoxication

  • FAS: Ethanol is oxidized by the fetus, producing acetaldehyde
  • Methanol intoxication: Methanol is oxidized to formaldehyde, which is even more toxic than acetaldehyde.

Explain and give examples of how catabolic and anabolic pathways can both be thermodynamically favourable

  • Biosynthetic pathways are inherently unfavourable, but this can be overcome by creating a high-energy precursor. One example of this is the precursor for glycogen synthesis uridine diphosphate glucose (UDP-glucose).

Describe the operations of the Cori cycle

  • Lactate is produced in skeletal muscle
  • transported by blood to the liver
  • converted to glucose by gluconeogenesis
  • transported back to muscle.

Describe the metabolic function and type of reactions involving each of the redox cofactors NAD+, FAD and NADP+

Define and give examples of integrated metabolic pathways

Integrated metabolic pathways are those that include one or more pathways working together to optimize various products. One notable example is the PPP (pentose phosphate pathway)

Describe the structure and metabolic role of glycogen

Structure

  • Glycogen is a polymer of glucose residues linked mainly by α(1-4) glycosidic linkages. There are α(1-6) linkages at branch points. The chains and branches are longer than shown.


Function

  • Storage method for glucose, buffer for blood-glucose concentration.

Describe how glycogen synthesis and degradation are controlled

See 1.c.

Define and give examples of high-energy biosynthetic precursors

See 3