Glycolysis

Question 1

Relate glycolysis to the overall map of metabolism and discuss its relevance.

Answer 1

• Glycolysis is the pathway that converts glucose to pyruvate, which is the metabolic precursor of Acetyl-CoA.
• This is a catabolic process and is needed to produce metabolic fuel in our tissues and cells. Our bodies need to maintain constant glucose levels in circulation to carry out its metabolic functions.

Question 2

Describe glucose entry into cells.

Answer 2

• Glucose can’t diffuse into cells.It is carried in by one of two transport mechanisms:

1. Facilitated diffusion: GLUT transport proteins in cell membranes. GLUT transporter proteins:
   - GLUT-1 brain & erythrocytes
   - GLUT-2 hepatocytes
   - GLUT-3 neurons
   - GLUT-4 adipose tissue & skeletal muscle
2. Na+-dependent co-transport SGLT

Question 3

How does glucose remain within the cell?

Answer 3

-Glucose is trapped by phosphorylation (glucose to glucose-6-phosphate).

-There are no cell-membrane transport systems for phosphorylated sugars.

• Phosphorylation is catalysed by:
  1. Hexokinase: most cell types
  2. Glucokinase: – liver & pancreatic islet cells

Question 4

Describe the reaction sequence of glycolysis.

Answer 4

Question 5

Describe the alternate metabolic uses of pyruvate.

Answer 5

Question 6

Describe the significance of the pyruvate dehydrogenase complex.

Answer 6

• The PDC occupies a key position in the oxidation of glucose by linking the glycolytic pathway to the oxidative pathway of the tricarboxylic acid cycle.
• It therefore plays an important role in energy homeostasis.

Question 7

Identify the steps at which regulatory processes occur in the glycolysis pathway.

Answer 7

1. The regulation of glycolysis is determined by the activity of the enzymes:
   - Hexokinase (or glucokinase)
   -Phosphofructokinase-1 (rate limiting step in glycolysis)
   -Pyruvate kinase
2. They catalyse irreversible reactions in the glycolysis pathway.
3. Their activity can be regulated (i.e., up- or down regulation) by metabolites and other intermediates, which are often part of feedback loops.

Question 8

What are the feedback loops that regulate glycolysis?

Answer 8

Question 9

Identify the steps at which chemical energy is captured.

Answer 9

Question 10

Describe a pathophysiological example: Hereditary myopathy with lactic acidosis.

Answer 10

• It is an autosomal recessive muscular disorder characterised by childhood onset of exercise intolerance with muscle tenderness, cramping, dyspnea, and palpitations.
• Concentrations of lactate & pyruvate in the blood increased disproportionately for the workload.
• Arterial alanine increases during exercise in patients as high levels of pyruvate are converted to alanine.