8. intergrated metabolism Flashcards
define anabolic pathways
synthesis of large molecules
uses ATP and NADH
define catabolic pathway
breakdown of large molecules
fuel oxidation
exergonic, makes ATP, waste products made
Metabolic homeostasis
control of balance between substrate availability and need by anabolic vs catabolic pathways
four basic types of metabolic pathways
fuel oxidation: glycolysis and TCA
fuel storage and mobilisation: glycogenesis and glycogenoylsis
Biosynthetic pathways
Detoxification/waste disposal pathways urea cycle
what are the normal levels of blood glucose
what happens if there is a significant decrease in blood glucose levels <60mg/dl
why does this occur
what happens if there is too much glucose
80-100 mg/dl
hypoglycemia, can enter coma
glucose influx lowers due to low Km of BBB transporters- need a lot of glucose to get past it
hyperosmolar effects= neurological defects and coma
- Concentration rises above renal tubular threshold
- Non-enzymatic glycosylation of proteins, sticking glucose to proteins which don’t need it- changes structure and function
3 ways the balance between use, release, storage by different tissues is achieved
- Blood [nutrient]: Fatty acids, Conc. determines whether skeletal muscle uses fatty acids or glucose.
- Hormones
- Central Nervous System: controls via pituitary gland with hormones or sympathetic
The two major hormones that regulate fuel storage & mobilization:
- Insulin: promotes storage of fuels (& use for growth)
- Glucagon: promotes mobilization of fuels
what tissues do insulin act on?
liver, muscle & adipose
what does insulin promote?
- Glycogen formation in liver & muscle
- Conversion of glucose to triacylglycerols (liver)
- Protein synthesis (e.g. albumin) in liver
- Storage of triacylglycerols (adipose)
- Increases glucose uptake by muscle & adipose
- Amino acid uptake & protein synthesis in skeletal muscle
what tissues do glucagon act on?
liver and adipose (muscles dont have receptors)
what does glucagon promote?
- Increased Glycogenolysis, reduced glycogen synthesis in liver
- Stimulates gluconeogenesis & ketogenesis
- Mobilises fatty acids from adipose triacylglycerols
which cells secrete insulin and glucagon?
- α cells secrete glucagon: ↓ Plasma [glucose] & ↑ [adrenaline]
- β cells secrete insulin: ↑ Plasma [glucose]
what is insulin synthesised as
insulin release:
insulin release modulation
preprohormone- C peptide is cleaved
- 80 mg/dL threshold
- Proportional release up to 300 mg/dL
- Rapidly degraded by liver
autonomic nervous system and vagus nerve
glucagon: what is it synthesised as
where is it degraded
regulation
what promotes release
preprohormone
degraded by liver and kidneys
seceretion regulated by [insulin] and [glucose]
released promoted by
- catecholamines (e.g. epinephrine)
- amino acids (so, meal composition is important)
Intracellular Events: Insulin
•Insulin autophosphorylates cell receptor
-receptor’s tyrosine kinase domain phosphorylates enzymes
•Basic cellular responses:
1) Reverses glucagon-stimulated phosphorylation
2) Kicks off a phosphorylation cascade
3) Induction/repression of enzyme
4) Stimulate protein synthesis
5) Stimulate glucose & amino acid intake