3. Glucose and Carbohydrate Metabolism (Part I) Flashcards
What is glucose converted to in order to store energy?
- Glycogen (short-term)
- Fat (long-term)
Which cells solely utilize glycolysis?
- RBCs
- They do not possess organelles to utilize the TCA cycle, lipid metabolism, etc.
Which tissues require glucose for proper function?
- Brain
- RBCs
- Mammary gland
- Fetus
- Spermatogenesis
What does the gut utilize as a fuel?
Glutamate (NOT glucose)
What is the consequence of advanced glycation end-products (AGEs)? Give an example.
- They may damage the function of the protein
- Ex: hemoglobin A1C
What is the precursor of amino acids’ carbon skeleton?
Glucose
What is the most basic amino acid? What is it made of?
- Alanine
- Pyruvate with an amino group
All of the amino acids in the body arise from ________, except for ________.
glucose
tyrosine
How is tyrosine produced? Why is it unique?
- Produced from phenylalanine as it gets hydroxylated on its aromatic ring
- Unique as it is the only amino acid that is NOT made from glucose
What does glucose prevent?
Ketosis
Why shouldn’t pregnant women NOT be on low-carbohydrate diets?
It is incredibly damaging to the fetus to lack glucose (possible ketosis could be fatal)
How is glucose absorbed? Where is it transported to?
- Absorbed within enterocytes
- Transported to the liver through the hepatic portal vein
What does the liver do with glucose?
- Store glucose as glycogen and/or
- Synthesize fat
What is the response of the pancreas to glucose?
Senses hyperglycemia, and produces insulin
What fuel sources may adipose and muscle utilize?
Either glucose or fat
What type of carbohydrate may be acquired from the diet?
- Fibre
- Starches
- Sugars
How much do carbohydrates constitute the AMDR?
45-65%
What should we emphasize concerning dietary carbohydrates?
- Emphasis on whole grains
- Emphasis on more fibre
- Emphasis of low-glycemic index carbohydrates (less simple sugars)
What dietary sources contain high amounts of glycogen?
There is no significant source of glycogen within the diet
Where is glycogen found?
- Liver
- Muscle
Differentiate hexoses and pentoses.
- Hexoses: 6 carbons
- Pentoses: 5 carbons (e.g. ribose)
What is the ratio for C:H:O in carbohydrates?
1:2:1
What is the chemical formula for hexoses? What is the formula weight?
- C6H12O6
- 180 grams
What are the single sugar units?
- Glucose
- Galactose
- Fructose
How does fructose differ from the other monosaccharides?
Fructose is a hexose, but it is a five-membered ring
How are glycosidic bonds produced? What are the different types?
- Dehydration reaction (removes an H2O) between carbon 1 and carbon 4
- Alpha bond
- Beta bond
Differentiate an alpha and beta glycosidic bond.
- Alpha bond: hydrogens are pointing on the same side
- Beta bond: hydrogens are pointing on opposite sides
What is sucrose composed of?
Glucose and fructose
What is maltose composed of?
Glucose and glucose
What is lactose composed of?
Galactose and glucose
What is the sweetness scale of monosaccharides and disaccharides (from high to low)?
- Fructose (twice as sweet as sucrose)
- Sucrose
- Glucose
- Maltose
- Lactose
How may sugars be used as a preservative?
Canned fruits in a sugar syrup tie-up free water, decreasing bacterial growth
Starches are polymers of ________.
glucose
What chains are present in amylose?
a(1-4) chains
What chains are present in amylopectin?
a(1-4) chains with a(1-6) branches
Does amylose or amylopectin have gel-forming abilities? Why?
- Amylopectin
- Due to their branching pattern, which allows them to hold more water
Fibre is acquired from _______.
plants
What is soluble fibre? Give examples.
- Soluble fibers form GELS
- Pectins (found in fruits) and oatmeal
What is insoluble fibre? Give examples.
- Forms the cell walls of plants, providing structure
- Cellulose, hemicellulose
What is functional fibre? Give an example.
- Fibre that has been added in food processing
- Psyllium is added to cereals to increase fibre intake
What is psyllium?
A functional fibre
What is the fibre requirement for men and women?
- Women: 25 grams
- Men: 38 grams
How much fibre does the Quebec population intake on a daily basis?
8 to 15 grams per day
What are the functions of soluble fibre?
- Delays gastric emptying
- Glycemic control
- Binds cholesterol and bile acids
- Fermented by colonic bacteria
Which type of fibre forms a viscous gel?
Soluble
How does soluble fibre increase glycemic control?
- Digestion and absorption take place over a greater length of time, and a greater length of the intestine
- Glucose is absorbed more slowly, allowing a more moderate increase in plasma glucose
How is soluble fibre linked to cholesterol status?
- Soluble fibre binds cholesterol and bile acids, which are excreted in feces
- This allows the body to synthesize more bile acids from cholesterol, which reduces cholesterol levels
How do we acquire energy from fibre, even if we don’t digest fibre?
Soluble fibre provides energy for the cells in the lining of the colon, as it is fermented by colonic bacteria
Which carbohydrate may influence the types of bacteria that populate the colon?
Soluble fibre
What are the functions of insoluble fibre?
- Provides bulk (laxative, water-holding effect)
- Delays gastric emptying (but does not form a gel)
- Some glycemic control (not as much as soluble)
- Binds cations
- Minor fermentation by colonic bacteria
What does insoluble fibre contain that binds cations? Which cations are bound? Is this a desired effect?
- Phytates (anions) bind cations
- Calcium, zinc, iron, and other positive minerals
- NOT a desired effect given the commonality and effets of these deficiencies
How is insoluble fibre negatively associated with iron absorption?
- The phytates bind iron
- Iron is already negatively absorbed from the start (10-15%)
How is fibre associated with softer stools?
- Fibre is hydrophilic, meaning that they hold onto water
- Fibre prevents water from being reabsorbed in the colon
- Produces a laxative-type effect
Where was the idea of glycemic index proposed? When?
- 1980s
- University of Toronto
Would an individual with a high-fibre intake excrete components from a meal faster than an individual with a low-fibre intake?
- High-fibre intake increases the speed of excretion
- It delays gastric emptying, but fibre increases the motility of the GI tract and speeds transit time overall
What does the glycemic index measure?
Measures how rapid, and how high, the blood glucose increases after consuming a standard amount of carbohydrate in food
What is the blood glucose level in the fasted state? What should it not go above?
- Fasted state: 5 mM/L
- Should not increase to over 10 mM/L
What is the standard of the glycemic index?
- Glucose
- Represents 100
How many salivary glands do we possess? What is their function?
- Six
- Moistens the food and helps us taste
What is the function of salivary amylase?
Breaks the a(1-4) bonds
Why are proteins, such as salivary amylase, no longer functional in the stomach?
Due to low pH, which changes the charges of the proteins
What does the pancreas release in response to food in the small intestine?
Pancreatic juice through the pancreatic duct into the duodenum
What is the function of bicarbonate in the pancreatic juice?
Increases pH, rising it to a slightly alkaline state
What is contained in pancreatic juice?
- Pancreatic enzymes (pancreatic amylase, glucoamylase, etc.)
- Bicarbonate
Where are disaccharides digested?
On the brush border of the small intestine (apical surface of enterocytes)
Describe the various layers of complexity to the small intestine.
- The tube itself has folds
- Every fold has villi
- Each villus has individual cells (columnar)
- The cells have finger-like projections (brush-border)
Where do surface enterocytes arise from? What is important about this process?
- Arise from crypts, migrate up, and are sloughed off the top
- The process takes three days, and is metabolically expensive
- But, it is important for the barrier to remain intact by the renewal of these cells
How do chylomicrons enter the lymphatic system?
Through the lacteal, and are dropped off to the heart for dilution
How do water-soluble nutrients enter circulation?
They are transported to the liver through the hepatic portal vein
What transports monomers into the enterocytes?
Active transporters
Which enzymes are contained in the mouth, small intestinal lumen, and small intestinal brush-border?
- Mouth: salivary amylase
- Small intestinal lumen: pancreatic amylase, glucoamylase
- Small intestinal brush-border: sucrase-isomaltase, lactase
How does lactose intolerance cause flatulence and diarrhea?
- Flatulence: lactose reaches the colon where it is fermented by bacteria, which produces methane, hydrogen, CO2
- Lactose and the resulting organic acids are strongly hydrophilic, which causes osmotic diarrhea
How may a breath hydrogen test diagnose whether an individual has lactose intolerance?
Hydrogen produced within the colon through bacterial fermentation may be reabsorbed back into the body and secreted in the lungs
Which enzyme deficiency results in the inability to digest lactose in the small intestine?
- B-galactosidase deficiency
- Since there are no other enzymes that can digest the B(1-4) glycosidic bond
What are the three types of lactose intolerance?
- Primary lactase non-persistence
- Secondary lactose intolerance
- Congenital lactose intolerance
What percentage of adults worldwide does primary lactase non-persistance affect? What is it?
- 70%
- After weaning, lactase is no longer produced
What causes primary lactase persistence? What kind of inheritance causes it?
- Mutation for lactase persistence
- SNP in the regulatory region (intron)
- Autosomal dominant
What is secondary lactose intolerance?
- Due to some pathology
- Ex: parasite infection, celiac disease, malnutrition
What is congenital lactose intolerance?
- Non-functioning lactase (from birth)
- Uncommon
- Infants must utilize lactase-free formula, and cannot drink breast milk
How did primary lactase persistence arise?
- When individuals (particularly in colder climates), in which ruminants were bred to produce milk, caused a genetic SNP
- Allows individuals to utilize the nutrients from another specie
- Nutrition influenced natural selection
How may Celiac disease cause lactose intolerance and malnutrition?
Destroys the villus architecture in the small intestine
Where are the SNPs for lactase persistence found?
- Not in the exon (target for mRNA)
- Found to enhance transcription from the lactase promoter
- Related to enhanced expression of the LCT promoter
What causes a milk allergy?
- Exaggerated immune response to proteins or to peptides found in milk
- IgE antibodies
- Mast cell degranulation
- Massive histamine production (anaphylaxis)
What is the driver of glucose absorption? Where are they contained?
- Na+/K+ ATPase
- Contained in large numbers on the basolateral surface of enterocytes
What is the function of the Na+/K+ ATPase?
- Transports 3 sodium ions out of the enterocyte
- Transports 2 potassium ions into the enterocyte
What allows SGLT1 to function? What is it?
- The electrochemical gradient generated by the Na+/K+ ATPase
- SGLT1 is the Na+/Glucose co-transporter
What kind of transport is SGLT1? What does it do?
- Secondary active transport, which transports a sodium and a glucose into the enterocyte together (symport)
- Sodium is moved down the chemical gradient
- Glucose is moved up the chemical gradient (low to high)
How is glucose transported from the enterocyte into the blood? What kind of transport is it?
- GLUT2
- Facilitated diffusion (uniport)
- Moves glucose down its concentration gradient (does not require energy)
Are enterocytes responsive to insulin?
No
What prevents the flow of substrates between enterocytes?
Tight junctions
Why is there no intracellular negative charge in enterocytes?
- Three sodiums are pumped into the blood by the Na+/K+ ATPase, while only two potassiums are pumped in
- A sodium ion is brought in by the sodium/glucose (SGLT1) co-transporter
How does glucose absorption affect water absorption?
Glucose is hydrophilic, and allows a flux of water to enter enterocytes
What would disfunction the GLUT2 transporter?
If plasma glucose concentration exceeded the concentration within enterocytes, glucose would not be able to travel through GLUT2 into the circulation (from high to low concentration)
What does glucose and galactose utilize to enter enterocytes? What about to exit?
- Enter: SGLT1 (secondary active transport)
- Exit: GLUT2 (facilitated transport)
Galactose undergoes preferential conversion to what?
Glycogen and glucose
Which transporter is responsible for fructose entry into the enterocyte?
GLUT5
Which transporters are responsible for fructose exit out of the enterocyte?
GLUT5 or GLUT2
What is the control point for glycolysis?
Phosphoglucokinase and fructose-1,6-bisphosphate
What is fructose preferentially converted to?
- Oxidized rapidly
- Or, if there is no need for energy, fructose undergoes de novo lipogenesis (conversion to FAs and TGs)
Why isn’t fructose metabolized to glucose?
Since it enters glycolysis downstream of the control point
Why may potential health complications occur from consuming a large quantity of fructose?
As it is preferentially converted to FAs or TGs, if there is no need for energy
What is stimulated as blood glucose increases?
Stimulates the B-cells of the pancreas to secrete insulin
Which glucose transporter is sensitive to insulin? Which tissues is it present in?
- GLUT4
- Muscle, adipose, heart
What does insulin stimulate as an anabolic hormone?
- Glucose oxidation
- Storage and conversion to fat
- Use of glucose as a fuel
- Glycogen synthesis
- Protein synthesis
What does insulin inhibit?
If there is an abundance of glucose entering the system, there is no need to synthesize more glucose (decreased gluconeogenesis)
What is the glycemic response to a high glycemic index food?
- Rapid increase and subsequent decrease of plasma glucose to below normal levels (rebound hypoglycemia)
- High insulin response
What is the glycemic response to a low glycemic index food?
- Moderate increase of blood glucose and insulin response
- Aid in the maintenance of a regular insulin response
How is glycogen related to water storage?
Glycogen is highly hydrophilic, allowing it to hold a large quantity of water
How is glucose activated for the synthesis of glycogen?
- Addition of a phosphate group on carbon-1
- Enzyme: UDP-glucose pyrophosphorylase
What does glucose-1-phosphate form for glycogen synthesis?
- Glucose-1-phosphate and UTP forms UDP-glucose and two inorganic phosphate groups
- Glycogen synthase catalyzes the elongation
Why does the increased storage of glycogen cause an increase in liver mass?
Because glycogen stores water as it is highly hydrophilic
Which enzymes catalyze glycogenesis and glycogenolysis? How does their activity fluctuate based on the addition of glucose?
- Glycogenesis (glycogen synthase): increases with the addition of glucose
- Glycogenolysis (glycogen phosphorylase): decreases with the addition of glucose
When ATP is unnecessary, what is the Acetyl-CoA generated from glucose utilized for?
- Lipogenesis
- May also be converted to cholesterol
Which fatty acids may be synthesized de novo? Which must be ingested?
- De novo: saturated and oleic fatty acids
- Ingested: polyunsaturated fatty acids
What are the consequences of fat accumulating within the liver?
- Causes the liver to increase in size
- Becomes paler in colour due to excess lipids
What may cause fatty liver?
Alcohol consumption or obesity
How is non-alcoholic fatty liver disease (NAFL) screened?
- Analyzing liver enzymes within the blood
- If there is damage to liver cells, liver enzymes leak out into the blood, allowing for diagnosis
What is non-alcoholic steatohepatitis (NASH)?
- Extends from NAFL
- Causes cirrhosis, in which scarring prevents the liver to function properly
What does the control point of glycolysis respond to?
- Insulin and glucagon
- Insulin: promotes flux through glycolysis
- Glucagon: limits flux through glycolysis
What is fructose converted to following ingestion?
Three-carbon intermediate (dihydroxyacetone phosphate), which lies beyond the control point
What is the primary hormone during a fast?
Glucagon
What is the effect of glucagon on glycogen stored in the liver?
Glycogen is degraded to glucose to feed peripheral tissues and the brain
What is the effect of glucagon on glycogen stored in muscles?
- Degraded to glucose to feed muscle tissues
- Glycogen from muscle stores are NOT exported in the plasma, and remains in muscle to feed exercising muscle in the fasted state
What are the primary effects of glucagon?
- Releases glucose from stores
- Degradation of glycogen in liver and muscle
- Degradation of triglycerides from adipose tissue
