Carbohydrate metabolism Flashcards
glucose uptake
into tissues - used for energy in brain
glycogen synthesis
triglycerides in adipose tissue
glycogen breakdown
glycogenolysis
glycolysis
glucose breakdown
gluconeogenesis
lactate from liver used
the pancreas
- Secretes hormone insulin into blood in response to an increase in blood glucose
- Exocrine - release digestive enzymes into ducts
- Endocrine - hormones - Islets of Langerhans - released into blood stream
what happens when glucose is in the blood?
• Some glucose taken up by liver via facilitated transport (uptake) - regulate gluc absorption
• Insulin activates hexokinase (glucokinase) to store glucose as glycogen (glycogen synthesis)
• Liver hexokinase reaction reversible so glucose can also leave liver cell (glycogenolysis and gluconeogenesis) to maintain blood glucose
- Use when not taking carb in diet
why do we need to maintain blood glucose?
• Glucose primary fuel source of brain cells (glycolysis), as well as turnover and neurotransmitter synthesis
• 2% of body weight, but consumes 20% of glucose, making it main consumer of glucose for body weight (6 mg/100 g tissue/min or 100-150 g/day)
• Normal diet 300 g/day, and liver stores around 100 g/day
- Astrocytes
- Not regulated by insulin
astrocytes
support cells to help neuron function - store glyc
how is most of the remaining glucose taken up
by skeletal muscle
skeletal muscle glucose uptake
• Glucose enters muscle via facilitated transport (uptake)
• Hexokinase (glucokinase in liver) phosphorylates glucose to maintain gradient
• Unlike liver, glucose-6-phosphate cannot leave cell and enters glycolysis or glycogen synthesis (500 g whole body)
- Doesn’t store as much as liver - can be manipulated with nutrition and ex
glucose transport via GLUT4
- GLUT4 translocated to plasma membrane from intracellular vesicles in response to insulin
- Muscle contraction also stimulates GLUT4 translocation to plasma membrane
- Calcium (Ca2+) thought to be main signal
glycogen synthesis
- Glucose-6-phosphate (G6P) converted to glucose-1- phosphate (G1P) by phosphoglucomutase
- Uridine diphosphate glucose (UDP-glucose) is synthesised from G1P and uridine triphosphate UTP
- UDP-glucose binds to pre-existing glycogen molecule or glycogenin and UDP is released
- Glycogenin is a protein at the core of a glycogen molecule that has autocatalytic (add to itself) activity
- Glycogen synthase and branching enzymes then form proglycogen, which grows into macroglycogen - rate limiting step
how does insulin stimulate glycogen synthesis?
- Switches protein phosphatase on
- Inactive as phosphorylated - blocks catalytic site
- Phosphatase removes phosphate
muscle contraction/how does exercise reduce glycogen synthesis?
- Kinase - phoshphorylates
- No food = no insulin = no glyc
how does insulin inhibit glycogen breakdown (glycogenolysis)?
- Glyc phosphorylase - rate limiting step
- Active = phosphorylated§
muscle contraction/how does exercise stimulate glycogen breakdown?
Insulin levels decrease
glycolysis preferential during exercise
• Calcium (Ca2+) and adrenaline main signals stimulating glycogenolysis
• Reduced insulin with exercise
• G6P derived from both
glycogenolysis and glucose uptake
• Enters glycolysis pathway (leaves liver by action of glucose-6- phosphatase)
gluconeogenesis - liver
- Liver is first and foremost reserve for maintaining blood glucose in postabsorptive period and during fasting
- Once reserve is exhausted (overnight fast can almost fully deplete liver glycogen stores), glucose must be made from non-carbohydrate precursors
- Circulating fatty acids and glycerol increase during fasting
- Unfortunately fatty acids cannot be a precursor as the pyruvate dehydrogenase and pyruvate kinase reactions are irreversible (i.e. acetyl- CoA from fatty acids cannot form glucose)
- Reversal of glycolysis?
- Acetyl-CoA from fatty acids plays an important role in inhibiting pyruvate dehydrogenase and diverting pyruvate to oxaloacetate and malate
- Lack of insulin relieves inhibition of muscle proteolysis to release amino acids, such as alanine
reversal of glycolysis
- Pyruvate kinase inhibited by alanine
- Glycerol is phosphorylated to glycerol-3-P via glycerol kinase
- Lactate produced at high rates in muscle during exercise, and also continuously in red blood cells
different carbohydrate sources for exercise
liver
ingested
skeletal muscle
maintain glucose at 5 mmol/l
liver carbohydrate source
o 100 mmol/kg
o 80-100g
o 320-400 kcals
o Replenished with just food
ingested carbohydrate source
o Up to 1000g/day
skeletal muscle carbohydrate source
o 50-100 mmol/kg
o 400-700g
o 1600-2800 kcals
o More than liver as muscles bigger
blood glucose at rest
- 80-100g in liver
- 0.1g/min
- Sink maintained at 5 mmol/l
- Glucose uptake in diff tissues at rest 0.1g/min
- Brain is biggest consumer
blood glucose during carbohydrate ingestion
Volume of sink increases
skeletal muscle glucose uptake increases during exercise
- Muscle contraction also stimulates GLUT4 translocation to plasma membrane
- Ca2+ main signal
- Regulated by ex intensity
blood glucose during prolonged exercise
Reduced volume of sink
liver glycogenolysis and glucose output increased during prolonged exercise
Exercise increases activation of the sympathetic NS
releases adrenaline
inhibits insulin release
inhibits glycogenolysis
glucagon stimulates glycogenolysis
carbohydrate oxidation during prolonged exercise
- Start using other fuels - muscle glyc
• Rate of carb ox cannot fuel muscle contraction - stop ex
why does glycogenolysis increase as exercise intensity increases?
- Increased AMP
- ATP only fuel used for muscle contraction
- Higher muscle contraction = higher breakdown
muscle and liver glycogen stores are finite and become depleted during exercise
can only be used for so long
blood glucose response to exercise with water or 1.5/min carbohydrate ingestion
- Stimulus greater than use at start
* Didn’t fatigue - maintain blood glucose and carb ox
glucose oxidation response to exercise with water or 1.5/min carbohydrate ingestiom
- Stimulus greater than use at start
* Didn’t fatigue - maintain blood glucose and carb ox
slowing down the rate of muscle glycogen use during exercise with 0.5/min carbohydrate
- Running
- ½ marathon pace
- 0.5g/min - carb 5.5% electrolyte solution - 500ml with 30g carb - tested Lucozade
- Spared glyc utilisation - run for another half hour - 33%
which type of carb is best to ingest?
- 3g/min
- Can’t ox more than 1g/min
- Rate of gluc ox stays the same regardless of amount digested
- W/ fructose (absorbed diff) - can get more into system and oxidise
how can glycogen loading increase exercise performance?
Ingest carb after ex - load up muscle
what is glycogen loading caused by?
increase in sensitivity of muscle to insulin
- Muscle contraction stimulates GLUT4 translocation to plasma membrane
- End of ex TCA cycle, PDC and glycolysis flux return to near resting, but GLUT4 maintained for several hrs post ex
- Glyc resynthesis highest in first few hrs post ex, but insulin sensitivity elevated for few days
when is glycogen resynthesis highest?
in hours after exercise
immediately after
