Gluconeogenesis Flashcards
Glycogen storage disease (GSD)
- Deficiencies in enzymes affecting either the glycogen synthesis (glycogenesis) or glycogen breakdown (glycogenolysis)
- Caused by genetic defects (mutations in chromosomes that cause changes in the coding of the enzymes)
- Frequency varies between animal and breed types
- Common symptoms
: Hypoglycemia (low blood glucose), Hepatomegaly (liver enlargement)- basically a lot of glycogen trapped in the liver, Glucagon insensitive (will stop glycogen breakdown) , Muscle weakness (glycogen in muscle= glucose molecules=ATP so lack of ATP means weak muscles)
Muscle GSD: type 7
Deficiency in muscle- Phosphofructokinase (PFK)
Causes glycolysis to slow down at step 3 due to a traffic jam where PFK is inefficient
Results in: PFK activity in muscle 1-4% = exercise intolerant AND PFK activity in RBC is 6-22% = hemolytic crisis
- Commonly reported in spaniel breeds
Hepatic GSD: Type I (Von Gierke’s disease)
Deficiency in glucose-6-phosphatase. Sits in the endoplasmic reticulum. Deficiency prevents the untrapping stage (removal of phosphate from glucose-6-phosphate to make glucose). Therefore, 90% of glucose is trapped in phosphorylated form and cannot go towards blood glucose levels
Overall inability to regulate blood glucose in response to glucagon/epinephrine
Hepatic GSD: Type I (Von Gierke’s disease) consequence
Results in:
Hepatomegaly (over production of G6P in liver caused because animal is still eating, gaining glucose, and storing it as glycogen in liver causing the Liver to fill up
Hypoglycemia- glycogen is unable to be turned back into glucose to be used in the blood stream
- Poor prognosis- puppies rarely survive, likely won’t see in clinic
Hepatic GSD: Type III (Cori’s disease)
Deficiency in 1,6-glucosidase. Unable to break down glycogen 1,6 branching chains into glucose (10% of total supply not being made into glucose to be put back into the blood)
Results in:
Similar to type I but not as severe
- Hepatomegaly
- Hypoglycemia
- Muscle weakness @ 2 months
- Most common in Akitas and German Shepards
Hepatic GSD: Type IV (Andersen’s disease)
Deficiency in glycogen branching enzyme (GBE) for the synthesis of 1,6 glycogen linear linkages Forms long links of linear glycogen (1,4) which has a low solubility.
The linear branches will precipitate in liver and accumulate there
Results in:
- weakness at birth
- eventual Liver dysfunction
More common in Norwegian forest cats, and American quarter horses
Myopathic GSD: Type V
Deficiencies in muscle glycogen phosphorylase
Results in the inability to breakdown 1,4 linkages for energy production
Causes:
- Exercise intolerance: rhabdomyolysis (muscle fibres in blood stream), severe dehydration, electrolyte imbalance
- During rest, animal may appear normal since they can use other energy stores (fatty acids)
Most common in Charolais cattle and Merino sheep
Hepatic GSD Type VI (Hers Disease)
Deficiencies in hepatic glycogen phosphorylase
Causes a reduced ability to breakdown 1,4 linkages
Consequences:
- Moderate hypoglycemia
- Ketosis
- Growth retardation
- Hepatomegaly
**Symptoms not as severe
Human adult brain glucose requirement
120-160 g daily dose
Glycogen supply is limited. Liver only has 1/2 day supply for the brain under fasting conditions
Gluconeogenesis
Body’s way of maintaining blood glucose in between meals because can’t rely on glycogen stores.
Occurs in liver and kidneys
Substrates used for gluconeogenesis
amino acids, lactate, glycerol, proprionate (ruminants)
Gluconeogenesis costs
Very expensive. Requires 6 ATP
Worth the energy costs as brain and RBCs can only use glucose for energy (and ketones)
Steps to gluconeogenesis
- Need to get oxaloacetate. Can turn pyruvate into oxaloacetate. Can also get oxaloacetate through amino acids, lactate, glycerol (from fat breakdown)
Pyruvate to oxaloacetate (pyruvate carboxylase)
Oxaloacetate to phosphoenol-pyruvate (PEPCK)
- Continues backwards through glycolysis
