Carbohydrate Metabolism Flashcards
What is Metabolic homeostasis?
The process of maintaining optimal metabolite concentrations and managing chemical energy reserves in tissues
What is Catabolism ?
The degradative phase of metabolism; releases energy
What is Anabolism (biosynthesis) ?
The building phase of metabolism: requires energy
What is the Blood glucose ideally kept at ?
~4.5mM (70−100 mg/100mL), with some fluctuation occurring after a meal
What is the brain most vulnerable ?
Hypoglycaemia as cerebral cells derive their energy predominantly from aerobic metabolism of glucose
When the brain is vulnerable to hypoglycaemia, it cannot ?
- store glucose in significant amounts or synthesise glucose
- metabolise substrates other than glucose or ketone bodies
- extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the
brain is not facilitated by hormones
Blood glucose varies relatively little over 24hr despite changes in food intake. Controlled by ?
Changes in circulating levels of insulin and glucagon
Alterations in the ratio of
insulin:glucagon within the blood are essential for ?
The maintenance of blood glucose
When is Glucose absorbed from the intestine ?
2-3 hours following a meal
When is Glycogen degraded?
Between meals and and lasts for 12-24 hours
During sleep/extended food deprivation there is a gradual dependence on ?
De novo glucose
synthesis by gluconeogenesis as glycogen stores are depleted
Blood glucose is under strict homeostatic control, by two main hormones ?
Insulin and Glucagon
Insulin stimulates ?
Glucose uptake and storage when levels are high
Glucagon stimulates ?
Breakdown of stores/synthesis when levels are low
How does glucose enter the cells ?
by facilitated diffusion i.e. it is a carrier-mediated process with glucose entering the cells down its concentration gradient
How is the entry of glucose mediated ?
Entry mediated by a family of glucose transporter proteins (Gluts) which are structurally related but encoded by different genes that are expressed in tissue specific manner
Explain GLUT 1 in detail and where it is found ?
- Found everywhere - all mammalian tissues
- Constitutive glucose transporter: basal glucose uptake
- High affinity (1mM), low capacity: glucose continually taken up at steady rate irrespective of the blood glucose concentration
Explain GLUT 2 in detail and where it is found ?
- Found in the liver and pancreatic beta cells
- Low affinity (15-20mM), high capacity: rate of glucose entry is proportional to the glucose concentration
- High plasma glucose leads to accelerated glucose entry.
- Low affinity prevents glucose entering the liver when blood glucose is low, allowing glucose to preferentially enter brain and red blood cells
Explain GLUT 3 in detail and where it is found ?
- Found mostly in the brain
- Supplements GLUT 1 in tissues with high energy demands
Explain GLUT 4 in detail and where it is found ?
- Found in the skeletal muscle and adipose tissue
- Affinity ~5mM, therefore controlled by the blood glucose concentration.
- Insulin-dependent: increases the number of transporters on the plasma membrane (so high
uptake when high blood glucose)
Explain GLUT 5 in detail and where it is found ?
- Found in the small intestine
- This is a fructose transporter by facilitating fructose absorption by moving the sugar down a chemical gradient
What is Glycogen ?
Polysaccharide storage form of glucose; mainly in liver and muscle
What is difference between the way Liver glycogen and Muscle glycogen are used ?
Liver glycogen is used to maintain plasma glucose levels between meals, whereas muscle glycogen is used for contraction
How is glycogen synthesised and degraded ?
- Glycogen is synthesised via glycogenesis
- Degraded via glycogenolysis, producing glucose-1-phosphate (G1P)
In the liver, what can G1P be converted to ?
Free glucose via G6P and exported into the bloodstream to maintain plasma glucose levels
Where is the G6P isolated ?
In the ER lumen, which allows use of concentration gradients for glucose and G6P to control flux out of the liver
Which has a greater tissue content, the liver or muscle ?
The tissue content of glycogen is higher in liver than muscle
Which has a greater muscle storage capacity, the liver or muscle ?
Muscle because of greater muscle mass
Why does the liver contain less glycogen than is required?
To sustain glucose metabolism for 24 hours therefore require de novo synthesis by gluconeogenesis (We require 200g glucose/day)
When can glycogen stores rise ?
After meal
When do the glycogen stores fall ?
Between meals as glucose is released from glycogen to help maintain blood glucose levels
After a meal, what is there an increase in ?
After a meal there is an increase in blood glucose; between meals it stabilises
What happens overnight to the glycogen stores ?
Overnight glycogen
stores are mobilised to help maintain blood glucose levels, with increasing glucose coming from gluconeogenesis
Explain the metabolism in the fed state (Liver) ?
- High concentrations of nutrients leads to an increase in the I:G ratio
- High blood glucose enters the liver and is converted to glycogen and triacylglycerols which are secreted as VLDL. Some enters TCA cycle
- Lactate returning from red blood cells and muscle, and glycerol from peripheral tissues, are also
converted to triacylglycerols - Excess amino acids entering from the gut are converted to pyruvate and metabolised via the TCA for energy or converted to triacylglycerols
Explain the metabolism in the fed state (Muscle) ?
- Glucose enters the muscle via insulin-stimulated Glut 4 and is converted to glycogen or metabolised to produce acetyl CoA and energy
- Fatty acids entering muscle via chylomicrons and VLDL are oxidised by beta-oxidation to acetyl CoA to produce energy to support contraction
- Amino acids are incorporated into proteins
Explain the metabolism in the fed state (Adipose tissue and Brain) ?
- Glucose enters adipose tissue by insulin-dependent Glut 4 and is converted via glycolysis and PDH into acetyl CoA and then to fatty acids and triacylglycerol
- Fatty acids enter from VLDL and chylomicrons and are converted to triacylglycerol
- Glycerol released from TAGs is returned to liver for re-use
- Brain takes up glucose via Glut 1 & 3 transporters and metabolises it oxidatively by
glycolysis and the TCA cycle to produce energy