2020A Question 11
An infusion of 50 mL of 50% dextrose is given to a healthy 70kg adult. Describe the possible metabolic pathways for the dextrose.
Examiner Report
In order to pass, an answer had to address the domains of:
- Glucose utilisation pathways
- Glucose storage pathways, namely glycogen and fat stores
- Hormonal regulation of the pathways, in particular the effects of insulin on target tissues.
While it was not necessary to provide detailed reactions of the metabolic pathways, credit was awarded for naming of major intermediaries, enzymes, receptors, relative amounts of energy released by different pathways and other relevant information. Many good answers used flow diagrams effectively to demonstrate the relevant pathways. Common problems and errors included:
- Entirely omitting one of the domains
- Limiting discussion of storage pathways to either glycogen or fat
- Incorrect utilisation of the terms “glycogenesis” and “glycogenolysis”
- Nomenclature of GLUT transporters, their locations and insulin responsiveness
- Calculation of the dose (ranging from 2.5g to 25,000g)
- Identifying dextrose as a carbohydrate polymer or molecule that needs to be broken down or converted to glucose
- Conversion of glucose to amino acids and/or proteins
- Discussion of an osmotic effect and ADH response
Model Answer
| Factor | Detail |
|---|---|
| Utilisation: | Occurs if ↓ insulin, ↑ glucagon Anaerobic: → 2 ATP (in all cells) |
| Glycolysis | |
| Krebs cycle | Pyruvate → Acetyl CoA and enters CAC, to produce: - 4 x NADH+ - 2 x FADH2 - 2 x GTP - 4 x CO2 |
| Oxidative phosphorylation | - 1x ATP - 1 x H2O |
| Storage: | Occurs if ↑ insulin, ↓ glucagon: -GLUT2: Constitutive GLUT4: Inducible |
| Glycogenesis | Uptake into liver (GLUT2), skeletal muscle (GLUT4) Dose is 25g. Limit is ~50g liver, 400g skeletal muscle Can be later catabolised to yield glucose |
| De novo lipogenesis | Uptake into liver (GLUT2), adipose (GLUT4) |
| Conversion: | |
| Lactate (Cori Cycle) | Hepatic gluconeogenesis from lactate |
| Amino acids (Cahill Cycle) |
Hepatic gluconeogenesis from alanine (produced from muscle protein degradation) |
| HMP shunt | For synthesis of nucleotides (ribose) |
| Rapoport-Luebering shunt | Production of 2,3-DPG in RBCs |
| Pathology: | |
| Urination | Renal threshold ~10mM may be exceeded if large dose Glycosuria continuous if taking SGLT2 inhibitor |
| Glycosylation | Chronic hyperglycaemia → Damage to proteins → Microvascular complications (nephropathy, neuropathy) |