fate of glucose Flashcards
give an overview of steps related to the metabolism of glucose after a meal
- Absorption of glucose from the intestines and transportation to the liver via the hepatic vein.
- The impact of high glucose levels on hormone levels
- Oxidation of glucose into energy
- Storage of excess glucose in the liver
- Conversion of excess glucose into triacylglycerols (TAG) and exportation out of the liver to adipose tissues
- The use of glucose as an energy substrate by the brain via aerobic glycolysis
- The use of glucose as an energy substrate by the red blood cells via anaerobic glycolysis
- Increased uptake of glucose into muscle cells and adipose cells for energy
- Increased glucose uptake by muscle cells for conversion into glycogen storage
- Triacylglycerol storage in the adipose tissue
how is blood glucose maintained
as fasting progresses, the liver produces glucose not only by glycogenolysis but also gluconeogenesis (pancreas releases glucagon)
what are the major sources of carbon for gluconeogenesis
- amino acids
- lactate
- glycerol
- fatty acids
when does an animal reach starvation state
after fasting for 3+ days
what happens if an animal has a prolonged period of low blood glucose
- coma
- death
due to lack of appropriate energy sources to maintain vital cells (esp CNS tissue which can only use glucose as a substrate)
where and into what are carbohydrates digested
- in the small intestine
- monosaccharides (including glucose)
- starts in mouth with salivary amylase
- glucose enters blood from SI and travels to liver via hepatic portal vein
what happens after ingestion and digestion od carbohydrates
the absorption of glucose from the small intestine into the bloodstream results in the elevation of blood glucose levels. This increase in blood glucose levels is detected by various cells, but chiefly the pancreatic islet cells.
The pancreatic islet cells respond by releasing insulin into the bloodstream. The aim of insulin is to decrease the concentration of glucose back to the normal levels of glucose in the blood. Therefore the message that insulin predominately sends to various tissues is to store glucose, as either glycogen or fats. The pancreatic islet cells releasing insulin are referred to as beta islet cells.
There is another hormone called glucagon, which is the hormone partner to insulin (i.e. it has the opposite effect to insulin, in that it mobilises stores of glucose when the blood glucose levels are low). High blood glucose levels have inhibitory effects on glucagon, thus reducing the circulating levels of glucagon. Glucagon is also released from the islet cells of the pancreas (alpha cells).
what happens to glucose in the liver
- absorbed by hepatocytes OR
- continues through liver and enters gen circ
list fates of glucose in the hepatocyte
- can be oxidised and be used as an energy source for the hepatocyte
- under the influence of insulin it can be converted to glycogen and stored in the liver. the liver however only has small and finite spae to store glycogen
- it can be converted into TAG ready for export out of the liver as it shouldnt be stored in liver (get fatty liver or hepatic lipidosis)
how is TAG exported out of the liver
- TAG cant be stored in liver
- packages TAG along with proteins, phospholipids and cholesterol into lipoprotein complexes known as very low density lipoproteins
- secreted into bloodstream
- either stored as adipose tissue or taken u by tissues for immediate energy needs
what is the lactate equation and how is it relevent
when lactate builds up in anaerobic respiration it needs to be converted to pyruvate which occurs through lactate dehydrogenase aiding the transmission of an electron from lactate to NAD to form NADH and pyruvate
- the equation will shift according to the levels of pyruvate, NADH and lactate present at any time point
what happens to the lactate prodcued by cells undergoing anaerobic glycolysis
- primarily taken up by liver and oxidised back to pyruvate
- pyruvate is used to synthesize glucose (gluconeogenesis) in the liver which is then returned to the blood
- or is oxidized to CO2 in the TCA cycle
what cells most commonly undergo anaerobic glycolysis
muscle cells at times when there is a low concentration of oxygen –> make lactate
what is the Cori cycle
the cycling of lactate and glucose between peripheral tissues and the liver
- cannot continue indefinitely as there is net loow from system (6 ATP used to make glucose in liver to deliver only 2 ATP to peripheral tissues
where does glycerol come from
obtained from lipolysis of adipose triacylglycerol
where do amino acids come from
the breakdown of protein (most degradation of muscle protein)
where does lactate come from
anaerobic glycolysis occuring in the cytosol of the RBCs
discuss anaerobic glycolysis in red blood cells
Glucose is the only fuel used by red blood cells, because they lack mitochondria. Fatty acid oxidation, amino acid oxidation, the TCA cycle, the electron transport chain, and oxidative phosphorylation (ATP generation that is dependent on oxygen and the electron transport chain) occur principally in mitochondria.
RBC, in contrast, use glucose to generate ATP from anaerobic glycolysis in the cytosol and, thus, red blood cells obtain all their energy by this process. In anaerobic glycolysis, the pyruvate formed from glucose is converted to lactate and then released into the blood. Without glucose, red blood cells could not survive.
outline the fate of glucose in the muscles
Exercising skeletal muscles can use glucose from the blood or from their own glycogen stores, converting glucose to lactate through glycolysis or oxidizing it completely to CO2 and H2O (see image below). Muscle also uses other fuels from the blood, such as fatty acids.
After a meal, glucose is used by muscle to replenish the glycogen stores that were depleted during exercise. Glucose is transported into muscle cells and converted to glycogen by processes that are stimulated by insulin.
what is the fate of glucose in adipose tissue
Insulin stimulates the transport of glucose into adipose cells as well as into muscle cells. Adipocytes oxidize glucose for energy. Adipose cells also metabolise glucose to Acetyl CoA in the adipose cells, which can be turned into fat and stored.
outline the steps that occur when low blood glucose is detected
- Decrease in glucose is detected and results in a decrease of insulin secretion and an increase in glucagon secretion from the pancreas
- The liver store of glycogen is converted to glucose under the influence of glucagon
3 and 4. The glucose from the glycogen serves as an energy substrate to the brain and red blood cells. The red blood cells produce lactate from anaerobic glycolysis, which in turn travels to the liver for gluconeogenesis (11).
- TAG is broken down in the adipose tissue into two compounds;
a) glycerol which is sent to the liver and converted to glucose
b) fatty acids which are sent to the muscle (6) and the liver (7) to be used as energy sources
- The incomplete oxidation of the fatty acids, results in the TCA cycle not being completed and intermediatary energy sources being produced, called ketone bodies (see later). These travel to the muscle cells to be used as energy.
what is the impact of fecreased blood glucose levels
Various cells detect that there is a decrease in glucose levels in the blood, including the pancreatic islet cells. This results in the inhibition of insulin production from the beta cells and an increase in the production and secretion of glucagon from the alpha cells into the circulation.
how is glucose released from glycogen
Glycogen can be found in the muscle and liver. The presence of glucagon stimulates the conversion of glycogen to glucose in a process called glycogenolysis. This glucose can then enter the circulation and be utilised by organs such as the brain and RBCS.
how does metabolism change in a starved state
In the starved state, the stores of glycogen have been depleted. The blood glucose levels are still low and glucagon is the dominating hormone.
In order to preserve the muscle mass of the animal, the body attempts to limit the amount of amino acids used for gluconeogenesis and relies more on ketones as a source of energy.
As there is very limited glucose, the brain must rely on using the intermediary energy source, the ketone bodies (KB). This results in elevated levels of blood ketone bodies and the animal is said to be in ketosis. This disease is common in dairy cows.
what does a high blood ketone and a low blood glucose level result in
The brain begins to take up these ketone bodies from the blood and to oxidize them for energy (the efficiency of this species dependent). Therefore, the brain needs less glucose than it did when merely fasting. Glucose is still required, however, as an energy source for red blood cells, and the brain continues to use glucose, which it oxidizes for energy.
Overall, however, glucose is “spared” (a prcoess referred to as glucose sparing). Less glucose is used by the body, and, therefore, the liver needs to produce less glucose per hour during prolonged fasting than during shorter periods of fasting.
Gluconeogenesis is the only process by which the liver can supply glucose to the blood if fasting continues.
what is protein sparing
The amino acid pool, produced by the breakdown of protein, continues to serve as a major source of carbon for gluconeogenesis. A fraction of this amino acid pool is also being used for biosynthetic functions (e.g., synthesis of heme and neurotransmitters) and new protein synthesis, processes that must continue during fasting. However, as a result of the decreased rate of gluconeogenesis during prolonged fasting, protein is “spared”; less protein is degraded to supply amino acids for gluconeogenesis.
what is the role of adipose tissue in starvation
- breaks down its TAG stores providing fatty acids and glycerol into the blood
- fatty acids serve as the major source of fuel for the body -> oxidised to CO2 and H2O by tissues such as muscle
- fatty acids converted to ketones by liver to be oxidised by many tissues including brain
discuss ketosis in dairy cows
Dairy cows produce large amounts of milk at around 6 weeks after calving; this is referred to as peak lactation. Cows can peak at more than 60L of milk per day. This requires a large amount of energy to make (5MJ per 1L of milk) and the cow is incapable of eating enough to support this level of milk production. Thus her body starts to mobilise fats to provide the energy to produce the milk and this results in the production of ketones. The mobilisation of the body fat reserves results in weight loss of the cow. If the cow loses too much weight (>50kg) or the levels of ketones in the blood are too high (due to large amount of fat being mobilised simultaneously), then this can have a large negative impact on the health of the cow.
how does the body adapt to the starvation state
During the fasting state into the starvation state, the body continues to mobilise fats as a main energy source for most tissues. The body will also continue to breakdown the proteins for amino acids for gluconeogenesis. However this breakdown of protein will become tissue, and even protein specific, to guard against vital proteins/cells becoming depleted in quantity. This occurs due to elevated levels of cortisol, resulting in the body adapting to the state of starvation
why do animals die of starvation
Protein can become so depleted that the heart, kidney, and other vital tissues stop functioning, or the animal can develop an infection and do not have adequate reserves to mount an immune response. In addition to fuel problems, they are also deprived of the vitamin and mineral precursors of coenzymes and other compounds necessary for tissue function. Because of either a lack of ATP or a decreased intake of electrolytes, the electrolyte composition of the blood or cells could become incompatible with life. Ultimately, death occurs.
what organ absorbs glucose
small intestine
where does gluconeogenesis predominently occur
liver
through which vessel is glucose transported into the liver
hepatic portal vein
