Carbohydrates Flashcards
What is the big picture of Energy Metabolism?
Burn sugar when available or use lipids when sugar absent. (see picture)
What is the history of catabolism?
Photosynthetic bacteria were able to breakdown glucose (glycolysis) in a time before oxygen
Fermentation
Reaction done by bacteria that produce ATP and small organic molecules in the absence of oxygen
- in the gut they breakdown glucose to produce acetate, lactate, butyrate, and other gases
What are the chemical properties of glucose?
-Water soluble, small - easy to transport in aq environment of cells
- osmotically active - drives H2O in and can dehydrate
- Has aldehyde group that makes it reactive
Maillard reaction
Sugars bond with amino acids
Why is glucose reactive?
The aldehyde group on the C1 anomeric carbon which undergoes ring conversion or mutarotation. In the linear form, sugars spontaneously react with amino groups
Which way is the OH group in alpha-glucose?
Down
Which way is the OH group on Beta Glucose?
Up
How do we detect reducing sugars?
Benedict’s reagent - used for detecting reducing sugars in urine (glucose, galactose, and fructose).
Sugar reduces the copper and coverts it to an acid (glucose to glucuronic acid)
Glycation
Glucose reacting with amino groups on proteins.
Spontaneous rxn and dependent on glucose conc.
Produces early glycation products (hemoglobin A1c)
Further reactions produce advanced glycation end products (AGEs) that bind to receptors and have signaling function
How can glycation cause damage?
Reactions from oxidative, metabolic, or radical stress cause more advanced glycation. The sugars can accumulate in areas or hang on to proteins where they are not supposed to be like blood vessel wall proteins
Glycosidic Bond
Bond connecting a sugar to a hydroxl group on another molecule
How do glycosidic bonds form?
First a sugar substrate is activated using energy (UTP) and catalyzed by UDP-Glucose pyrophosphorylase
Then, glycosyltransferase form glycosidic bonds using activated sugar nucleotides as substrates and UDP is released.
What happens to C1 after glycosidic bond has formed?
The ring does not open anymore so no more mutarotation.
Hydroxyl group on C1 remains in either alpha or beta position.
How are glycosidic bonds named?
Sugar contributing to anomeric carbon
Position of hydroxyl goup
Positional number of carbons connected by bond
Sugar contributing hydroxyl group
What is the nomenclature for maltose?
Glucose-alpha(1,4)-glucose
What is the nomenclature for lactose?
Galactose-beta(1,4)-glucose
What is the nomenclature of sucrose?
Glucose-alpha(1, beta2)-fructose
What are the two ways to break a glycosidic bond?
Hydrolysis
Phosphorolysis
Phosphorolysis - where does it occur and what does it do?
Use phosphate to cleave bond. Conserves energy of glycosidic bond in a phosphate ester bond
Requires regulated enzymes and phosphate
Occurs inside of cells during breakdown of storage carbs
Hydrolysis - what it does and where it occurs?
Use of water to cleave bond. Does not conserve the glycosidic bond energy
Occurs in the intestine during digestion of complex carbs
What are large digestible polysaccharides?
Starch/amylopectin in plants
Glycogen in animal tissue
What does starch consist of?
alpha(1,4)-linked glucose
What does glycogen and amylopectin consist of?
alpha(1,4)-linked glucose with alpha (1,6)-linked glucose branches
What are indigestible carbohydrates?
Cellulose
What is cellulose made of?
Beta(1,4) linked glucose
What occurs with indigestible cellulose?
Gut bacteria ferment all carbs and produce short chain fatty acids and gas
What is the presentation and what are diagnostic clues for patients with carbohydrate digestion disorders?
Pt presents with chronic digestive difficulties following intake of carb; diarrhea, bloating, and gas.
Diagnostic clue is the trigger of episodes
What is the pathology of patients with carbohydrate digestion disorders?
Enzyme deficiencies impair digestion and uptake of particular carb - no rise in serum glucose following ingestion
Osmotic activity of undigested molecules - draws water into intestine, diarrhea
Microbiome activity produces gas and acids (H2, CO2, bloating, pain)
Digestion of polysaccharides
Complex carbohydrates are hydrolyzed to monosaccharides
What happens to monosaccharides after they are hydrolyzed from complex carbs?
Monosaccharides are taken up by glucose transporters in the intestinal epithelium
What two types of enzymes do humans have for carb digestion?
alpha-amylases
disaccharidases
alpha-amylases
Break down large, alpha-linked polysaccharides (glycogen and starch granules)
Starts in mouth (saliva) and continues in intestine
Disaccharidases
Break down the three main dietary disaccharides
What are the three dietary disaccharides? What monomers are they made of?
Lactose - milk, Gal-Glu
Sucrose - fruit, Glu-Fru
Maltose - starch, Glu-Glu
What enzymes break down the three dietary disaccharides and what do they produce?
Lactose - Lactase - Galactose, Glucose
Maltose - Maltase - Glucose, Glucose
Sucrose - Sucrase/Isomaltase - Fructose, Glucose
What are the microbes in the gut and what do they do?
Most are anaerobes and operate by fermentation
Actively convert complex carbs to short chain fatty acids like butyrate, H2, CO2, methane
Case: A 24 year old presents with complaints of recurring abdominal pain for 4 months. Pain occurs after eating at favorite ice cream shop but also after having dairy. Pt has no rise in blood sugar, H2 detectable in breath, and acidic stool.
What is the dx? Explain onset and what helps
DX: Lactase non-persistance or Lactose intolerance
Lactase activity decline with age and eventually becomes insufficient. Early adult onset typically, but can have congenital lactase deficiency (lactase mutation, rare, present at birth)
Lactase preparations can help
What are legumes rich in? Can this be digested?
Raffinose.
Raffinose has alpha-1,6-galactosidic bond and cannot be digested
Galactosidase supplements can help
What 3 carbohydrates are taken up efficency?
Glucose
Galactose
Fructose
How is glucose taken up?
Uptake of glucose in cells of intestine and kidney is secondary active (against gradient)
Uptake into all other tissues is by facilitated diffusion (with gradient, requires phosphorylation)
What carbs share transporters?
Glucose and galactose. Fructose has separate transporter
How does facilitated diffusion of glucose occur?
Works if there is a concentration gradient. The cells keep the gradient by keeping the concentration of glucose very low by phosphorylating it to glucose 6-phosphate
Glucose –> Glucose 6-phosphate
How does this occur?
Most cells use hexokinases
Liver uses glucokinase
Hexokinases
Convert glucose to glucose 6-phosphate in most cells. Inhibited by its end products and uptake of glucose stops when glucose 6-phosphate cannot be processed
Glucokinase
How liver converts glucose to glucose 6-phosphate. Not inhibited by end product and liver takes up glucose all the times
What happens to unphosphorylated glucose?
Coverted to sorbitol, which is osmotically active
What is the distribution of glucose and fructose?
Serum glucose kept constant, at high level. Glucose uptake needs active transport to concentrate glucose in epithelial cells
Serum fructose concentration is low - passive uptake uses gradient
What protein absorbs glucose from the intestinal lumen into the intestinal epithelium?
SGLT1. Sodium pumped out of epithelium through use of ATP
What protein transports glucose into circulation?
GLUT2. Follows conc. gradient
How does glucose get transported from intestinal lumen to the cells?
Glucose via SGLT1 enters intestinal epithelium
Glucose then enters circulation via GLUT2
Glucose then heads to cells where it becomes glucose 6-phosphate
What protein transports fructose into the intestinal epithelium from the lumen?
GLUT5, follows conc. gradient
How does fructose get transported from intestinal lumen to the liver?
Fructose enters epithelium via GLUT5
Fructose enters circulation and then the liver where it becomes fructose 1-phosphate
Where does secondary active transport for uptake of carbs occur?
Intestine - SGLT1
Kidney -SGLT2
What transporters allow uptake by facilitated diffusion? What are the different types?
GLUT
GLUT2 - active in liver, intestine, pancreas
GLUT4 - insulin-inducible transporter
GLUT5 - fructose transporter
