Feeding and Fasting Flashcards
Why do carbohydrates provide for diets? Why is this?
While carbs are not an essential nutrient, they provide the majority of energy in most diets and are the least expensive source of calories. This is because of photosynthesis.
6CO2 + 6H2O + 673 KCal (solar E) —> C6H12O6 + 6O2
Animals would not exist without this capture of energy and production of oxygen.
Starch and cellulose are major energy storage forms in plants.
Which tissues preferentially oxidize glucose for energy?
- Brain (will also use ketones in long term in necessary if the body is fasting)
- red blood cells (no mitochondria, cannot burn fat)
- leucocytes (immune cells)
- gonads
- gravid uterus
What type of regulation is glucose under?
homeostatic regulation
- moderate acute hypoglycemia can lead to a decrease in brain function
- severe hypoglycemia can lead to coma or death
- high blood glucose can cause tissue damage
Why is blood glucose so important?
Blood glucose is the most important vehicle for moving energy in the body in absorptive and non-absorptive states (fed and fasted).
Sources of blood glucose vary with:
- type of GI tract
- diet
- time after eating
What do sources of blood glucose vary with?
- type of GI tract
- diet
- time after eating
Compare and contrast glucose absorption between a ruminant and non-ruminant. (ex. sheep vs. pig)
Ruminants like sheep will not absorb much glucose because the rumen microbes convert most of it to VFAs that are absorbed in the rumen. Therefore, little glucose is absorbed in the small intestine of ruminants.
In contrast, non-ruminants are able to absorb much more of the glucose they consume.
What happens to plasma glucose after a meal?
It increases from absorption (absorptive phase, see chart pg. 8)
How is starch broken down?
Salivary amylase breaks starch down to maltose and glucose.
Intestinal alpha amylase breaks down starch and intestinal maltase breaks down maltose into more glucose.
Breakdown of starch is a two step process.
How is sucrose broken down?
The enzyme sucrase breaks sucrose down to glucose and fructose.
How is lactose broken down?
The enzyme lactase breaks down lactose into glucose and galactose.
What is lactose intolerance and why do many animals have it?
Lactose intolerance is when the body cannot break down lactose since they do not have the lactase enzyme. It can still be fermented to a degree, but too much can cause issues like abdominal pain.
All mammals are lactose intolerant because they secrete lactose when they are young in order to take advantage of milk and colostrum, but stop producing lactase later in their development.
Describe general carbohydrate digestion in young animals.
Except for in newborn animals (24-48 hours), no di-, tri-, or polysaccharides are absorbed.
- immunoglobins are absorbed for passive immunity in the first 24 hours
- “leaky gut” allows immunoglobulins to be absorbed rather than digested after the young animal drinks colostrum within the first 24 hours of life, which establishes immunity
Describe carb digestion.
Carbs are digested to simple sugars, then absorbed into the enterocyte.
Except for in newborn animals (24-48 hours), no di-, tri-, or polysaccharides are absorbed.
Glucose transporters are required to move glucose, a polar molecule, across the cell membrane.
Active transport of glucose across the small intestine via Na-dependent glucose transporer SGLT1. It uses Na/K ATPase pump to create a gradient, allowing glucose to be transported into the cell.
Passive transport of glucose by GLUT2 proteins out of the epithelial cell into blood vessels (facultative transport that does not require ATP)
Describe the function of SGLT1
SGLT1 is a Na-dependent glucose transporter. It uses a Na/K ATPase pump, which creates a concentration gradient allowing for the active transport of glucose into the cell.
Describe the function of GLUT2
GLUT2 facilitates the passive transport of glucose out of the epithelial cell and into the blood vessels via facultative transport (no ATP) when glucose is in a higher concentration in the cell than in the blood
What is Vmax?
“How fast the enzyme can go”
Varies by different enzymes.
What is Km and what relationship does it have with the enzyme and substrates?
Km is the substrate concentration at half the maximal rate. It is a measure of the affinity of the enzyme for the substrate.
Low Km correlates with high affinity.
High Km correlates with low affinity.
Km varies by different enzymes.
What is nutrient partitioning?
The directing of nutrients to different tissues, i.e. where the nutrients is going.
Regulation of cellular glucose uptake is an example of nutrient partitioning.
How does GLUT vary?
GLUT isoforms have tissue specific expressions.
They are slightly different variations of the same ancestral gene.
They differ in regulation (ex. responsiveness to insulin) and biochemical properties (Km and Vmax)
Describe the brain’s relationship with glucose and its glucose transporter.
GLUT3 works with the brain. It has a low Km value, and therefore a high affinity for glucose. This is a good relationship since glucose is necessary for the brain to have and it can work well with little glucose present.
Describe the liver and its relationship with glucose and its transporter.
The liver utilizes GLUT2, which has a higher Km and therefore a lower affinity. Therefore, it works better when there is a higher concentration of blood glucose.
Which glucose transporter do general tissues use?
GLUT1, which has a medium Km value that is between that of GLUT3 and GLUT2.
Describe the relation between glucose transport and fat.
Fat works with GLUT4, which has the lowest Km value and the highest affinity for glucose. This is because when insulin “puts away” glucose, it works until the BG goes too low.
How is glucose metabolized?
Glucose is metabolized in catabolic and anabolic pathways.
- Catabolism
a. glycolysis: Glucose —> pyruvate
b. oxidation: pyruvate —> CO2 + H2O
c. pentose phosphate: glucose —-> NADPH - Anabolism
a. glycogen synthesis (short term energy store)
b. lipid synthesis (long term energy store)
Provide an overview of glycolysis.
Glycolysis takes a 6 carbon glucose to two 3 carbon pyruvates. It occurs in the cytoplasm of every cell in the body, and glucose is the predominant substrate (comes from glycogen, fructose, other sugars converted to glucose)
Glycolysis has 10 steps. Not all of them are regulated, but all of them are essential.
Glycolysis is also called the Emden Meyerhoff Pathway
See pg. 20 in this lecture for flowchart of glycolysis
What are near-equilibrium reactions?
Substrate quickly flows through and is not regulated
What are non-equilibrium reactions?
Large free energy changes and regulated rxns.
“the dam in the river”
What is hexokinase (glucokinase) and how is it related to glycolysis?
Hexokinase is an enzyme activated by insulin. It phosphorylates glucose, allowing it to be trapped in the cell as long as the phosphorous molecule is on it. It has tissue specific isoforms with different Km values and regulations.
This is the first enzyme in glycolysis and is a committed, regulated step.
What is the function of Phosphofructose Kinase (PFK)?
PFK is a key regulated step in the middle of the glycolysis pathway. It phosphorylates fructose 6-phosphate
Where does the removal of phosphorous from glucose occur?
Only in the liver and kidneys (sometimes in the intestines too)
Describe the movement of pyruvate during the events of glycolysis.
Before complete oxidation, pyruvate moves form the cytosol to the mitochondria.
It provides acetyl CoA and oxaloacetate, key intermediates, to the TCA cycle.
What is the function of pyruvate dehydrogenase?
Pyruvate dehydrogenase is an enzyme that converts the 3C pyruvate to a 2C acetyl CoA molecule along with CO2 and H2.
What is the function of pyruvate carboxylase?
Pyruvate carboxylase is an enzyme that converts pyruvate to oxaloacetate.
How is the TCA cycle regulated?
TCA cycle is regulated to maintain constant energy status.
It is regulated by the availability of substrate (acetyl CoA and oxaloacetate) and cellular energy status (NADH and ATP).
Low energy increases the cycle
High energy decreases the cycle
Provide a summary of the TCA cycle
4C oxaloacetate (OAA) condenses with acetyl CoA.
Net input: acetyl CoA
Net output: 2CO2 + 1GTP + 4 pairs of electrons
The output goes to the electron transport chain for oxidative phosphorylation, where more ATP is made.
How much ATP does the complete oxidation of glucose yield?
~ 36 ATP
Glucose + 6O2 —-> 6CO2 + 6H2O + 36 ATP
The efficiency of energy capture as ATP is around 39%, with remaining energy lost as heat.
How is extra glucose stored?
It is first stored as glycogen for later use.
What is glycogenesis?
This is glycogen synthesis from glucose.
It is predominantly increased by insulin and the availability of glucose-6-P.
What is glycogen synthase?
Glycogen synthase is a key regulated enzyme that adds one glucose at a time to the end of a chain when making glycogen.
Insulin turns glycogen synthesis on by phosphorylation.
There is an allosteric control (feed forward regulation) associated with this, as high cellular glucose-6-phosphase increases the rate of synthesis of glycogen.
Why is glycogenesis a “futile cycle?”
Glycogen is being made to be broken down later. It is energetically wasteful, but for very small losses.
How is glucose stored in the long term?
It is stored as fat
“De novo” (from scratch) synthesis occurs
Both carbon and reducing equivalents (NADPH) is needed for this process. The overall process is increased by insulin.
Once converted to fat, glucose cannot come back from it.
When fasting (post-absorptive), where do animals get glucose from?
- breakdown of glycogen (glycogenolysis)
- about a day of energy needed is in glycogen - make glucose from glucogenic precursors (gluconeogenesis)
What is glycogen phosphorylase?
This is an enzyme involved in glycogenolysis. By adding a phosphate to the glycogen, glucose is produced along with a P and glycogen.
What is glucose-6-phosphatase?
Glucose-6-phosphatase is an enzyme that removes phosphate from glucose so it can leave the cell and inter the bloodstream. This enzyme only works in the liver and kidneyes.
What is gluconeogenesis?
The synthesis of glucose from non-hexose precursors.
It occurs mainly in the liver, but also in the kidneys.
Describe gluconeogenesis in nonruminants.
The rate varies inversely with the rate of glucose absorption (if absorbing glucose, not making any)
Precursors come from body tissues and storage.
Describe gluconeogenesis in ruminants.
Ruminants utilize this pathway even in the fed state.
The rate of gluconeogenesis is always relatively high, especially soon after feeding when the main precursor is propionate.
What does the substrate for gluconeogenesis depend on?
The animal (fermenter or nonfermenter) and fed vs. fasting.
some sources include propionate (important for ruminants), glycerol, amino acids, and lactic acid
What do it mean when we say that there is no reciprocal regulation of synthesis and breakdown of glucose?
Both do not happen at the same time
What is Phosphoenolpyruvate Carboxykinase (PEP-CK)?
PEP-CK is an enzyme that converts oxaloacetate to phosphoenolpyruvate, which can be converted to pyruvate. It is a major enzyme of gluconeogenesis.
How are PEP-CK and pyruvate carboxylase regulated?
Gene and protein expression (increased expression when fasted, decreased when fed)
Allosteric regulation by substrate and products
Where does the energy for gluconeogenesis come from?
Break down of glucose would make this a futile cycle, so glucogenic amino acids are used to make glucose.
Fatty acids and ketogenic amino acids can also be oxidized. This results in ketone formation. The ketones are exported from the liver.
What relationship does T2D have with gluconeogenesis?
T2D fails to shut off gluconeogenesis, resulting is high glucose and high ketones. (sweet smelling breath)
