Carbohydrates Flashcards
Where are carbohydrates digested?
- Polysaccharides begins in the mouth via salivary alpha-amylase
- Disaccharides begin in the small intestine via brush border enzymes and pancreatic alpha-amylase
Which gland secretes amylase?
Parotid gland
What are the brush border enzymes?
Lactase
Sucrase
Maltase
a-dextrinase
How are digested carbohydrates absorbed?
- Absorbed via transmembrane transporters (SGLT1, GLUT5, GLUT2) in enterocytes
- Monosaccharides are water soluble and can be absorbed immediately into portal blood
After absorption most of the fructose and galactose are converted into glucose in the liver.
What happens after absorption of carbohydrates?
- After absorption, glucose, fructose, and galactose are transported through the portal vein to the liver
- Liver converts most galactose and fructose into glucose
Where does glycolysis take place?
What is the function of glycolysis?
What is the end product of glycolysis?
Cytoplasm of cells
Convert glucose into pyruvate for further processing into energy
Pyruvic acid - can be converted into acetyl CoA which will enter citric acid cycle
Where does the citric acid cycle take place?
What is the function of the citric acid cycle?
Mitochondrial matrix
Produces energy via aerobic respiration
- Acetyl CoA is degraded into CO2 and H
- H used to create NADH which can participate in oxidative phosphorylation reactions to form ATP in the mitochondria
How is glycolysis regulated?
What increases/decreases PFK activity?
Primarily by inhibition of phosphofructokinase
ADP, AMP increase PFK activity
ATP and citrate decrease PFK activity
What is the function of phosphofructokinase?
F6P to F-1,6-diphosphate
What is an alternative path for glucose to enter instead of glycolysis?
Hexose monophosphate shunt
- About 30% of glucose processing
What are the products of hexose monophosphate shunt? What is hexose monophosphate shunt mediated by?
NADPH and ribose-5-phosphate
Activity of G6PD
What is G6PD sensitive to?
- High carb
- Allosteric inhibition (NADPH) and activation (NADP+)
What happens in anaerobic conditions for glucose processing?
Anaerobic Glycolysis and the Cori Cycle
1. Lactate is produced when there is a buildup of pyruvate and NADH/H
2. Lactate is generated in peripheral tissues and then transported to liver
3. Removal of lactate from cell allows glycolysis to continue
4. Liver converts lactate to glucose
- Lactate dehydrogenase converts lactate to pyruvate
- Pyruvate is converted to glucose by gluconeogenesis
What happens to excess glucose?
- Stored as glycogen in liver and muscle cells
- Further excess converted to fat (liver) for storage
How is glucose polymerized to glycogen?
- Glucose to G6P by glucokinase
- G6P to G1P by phosphoglucomutase
- G1P to uracil-diphosphate glucose by UDP-glucose pyrophosphorylase
- Uracil-diphosphate glucose to glycogen by glycogenin, glycogen synthase, glycogen branching enzyme
What term describes the breakdown of glycogen to release glucose?
Glycogenolysis
What is glycogenolysis used for?
To maintain glucose levels between meals
What is glycogenolysis catalyzed by?
Phosphorylase
What is phosphorylase activated by and when is it not active?
- Inactive at rest
- Activated by two hormones: epinephrine and glucagon
What happens when there is low stores of carbohydrates?
Gluconeogenesis - maintains blood glucose concentration when carbohydrate stores are low
- Glucose is formed from amino acids and glycerol
What is the major site of gluconeogenesis?
Liver
How is gluconeogenesis regulated?
Rates of gluconeogenesis is increased when there is low blood glucose concentrations and when there is low carb stores in cells. Cortisol also promotes gluconeogenesis.
What are the major hormones?
Cortisol
Glucagon
Epinephrine
Insulin
Growth hormone
Where is the Islets of Langerhands located?
Endocrine pancreas
What do the alpha cells, beta cells, delta cells, episolon cells and gamma cells produce in the islets of langerhands?
alpha - glucagon
beta - insulin
delta - somatostatin
epsilon - ghrelin
gamma - pancreatic polypeptide
What is the precursor of insulin?
preproinsulin
How is C-peptide produced?
In beta cells, RNA translation produces preproinsulin which is then processed into insulin which also produces C-peptide in a 1:1 ratio. Both insulin + C-peptide packaged into secretory granules.
Secretion of insulin and C-peptide granules are stimulated by?
glucose
What are the half lives of insulin and C-peptide in circulation?
Insulin - 3-5 min
C-peptide - 30-35 min
What are the actions of insulin?
- Promote anabolism
- Promote glucose uptake into cells, glycolysis, glycogen synthesis and storage
- Increase protein and triglyceride synthesis in the liver - Inhibit catabolism
- Inhibit glycogenolysis, gluconeogenesis, ketogenesis
Low blood glucose concentration stimulates what hormone?
Glucagon by alpha cells
What does glucagon stimulate?
- Glycogenolysis by promoting hepatic phosphorylase
- Promotes gluconeogenesis by activating
- Enzymes involved in gluconeogenesis
- Many enzymes for aa mobilization
- Adipose cell lipase for FA mobilization
Where is cortisol produced?
Zona fasciculata of the adrenal cortex
What is the major glucocorticoid?
Cortisol
What is the function of cortisol?
Stimulates gluconeogenesis
1. Increase enzymes that convert aa into glucose in the liver
2. Increase mobilization of aa from extrahepatic tissue
Decrease rate of glucose utilization by cells
1. Reduced ability to convert NAD -> NADH
Decrease sensitivity of tissue
1. Reduce glucose uptake and utilization
Promotes protein and fat breakdown
- Increase amino acid and FA mobilization
What is the net effect of cortisol?
- Increased rate of gluconeogenesis
- Decreased rate of glucose utilization
- Blunted sensitivity to insulin
Increase BGC
What stimulates the release of cortisol?
- Stress stimulates hypothalamus to produce CRH.
- Low carbohydrates and CRH from hypothalamus stimulate anterior pituitary to produce ACTH.
- ACTH stimulate the adrenal cortex to produce cortisol.
- Cortisol inhibits the hypothalamus and anterior pituitary from producing CRH and ACTH.
Where is epinephrine secreted? What kind of hormone is it?
Adrenal medulla. Stress hormone.
What are the actions of epinephrine?
- Promote glycogenolysis - increase plasma glucose conc.
- Promote activation of lipolysis - incr. plasma FA conc
Growth hormone can be thought of as an…
Insulin antagonist
What is the function of GH?
Increase BGC by
1. Decreasing glucose uptake in skeletal muscle, fat
2. Stimulating gluconeogenesis and glycogenolysis
3. Causing insulin resistance
What are the signs of hypoglycemia from the autonomic nervous system?
Trembling, anxiety, diaphoresis, hunger
What are the signs of hypoglycemia from the central nervous system?
Dizziness, tingling, difficulty in concentration, blurry vision
What is the Whipple’s Triad?
Used to define hypoglycemia
1. Blood glucose < 4
2. Development of neurogenic/neuroglycopenic symptoms
3. Symptoms responding to administration of carbohydrates
What are the complications of hypoglycemia?
- Proinflammation leading to platelet activation and decreased fibrinolysis (prothrombosis)
- Increased heart rate, systolic BP, myocardial contractility, stroke volume, cardiac outputs
What is the treatment of hypoglycemia?
Administer carbohydrates
1. 15 g glucose increased blood glucose of 2.1 mmol/L in 20 min
2. 20 g glucose increases blood glucose of 3.6 mmol/L in 45 min
What are the cause of hypoglycemia?
- Drug induced hypoglycemia
- Hormone deficiency
- Severe illness
- Paraneoplastic production of IGFII
- Hyperinsulinism (endogenous and exogenous)
- Inborn errors of metabolism (GALT deficiency, GSD)
What is drug induced hypoglycemia?
Most frequently in patients with diabetes mellitus on glucose lowering medications (exogenous insulins, insulin secretagogues)
Other drugs can cause hypoglycemia in non-diabetic individuals
1. Pentamidine - causes pancreatic b-cell toxicity
2. Beta-blockers (epinephrine antagonist) - opposes glycogenolysis induced by catecholamines
3. Ethanol - inhibits gluconeogenesis and increases glycogen phosphorylase
What is an example of a hormone deficiency that leads to hypoglycemia?
Addison’s Disease (Adrenal insufficiency)
What kinds of severe illness can lead to hypoglycemia?
Hepatic disease and cardiac failure
How does hepatic disease/cardiac failure cause hypoglycemia?
- Impaired gluconeogenesis
- Decreased oxygen to hepatocytes
- Impaired insulin clearance causing prolonged half life
- Shunting of portal blood into systemic circulation
What is paraneoplastic production of insulin-like growth factor II?
NICTH - Non-islet cell tumor hypoglycemia causes hypoglycemia w/o insulin
Associated with increased paraneoplastic production of IGF-II
- Hypothesized that elevated IGF-II increases glucose utilization and suppressed endogenous glucose production
What causes hyperinsulinism?
- Insulinoma
- insulin-secreting beta cell tumour
- type of functional tumor - Congenital hyperinsulinism
- dysregulation in insulin secretion - Autoimmune insulin syndrome (AIS)
- Ab to insulin in patients who have not been treated with insulin
- Insulin secreted after meals binds to Ab causing retention in circulation
- Insulin dissociates from Ab ➔ hyperinsulinemia and hypoglycemia
What is GALT deficiency? What are the symptoms?
Deficient in galactose-1-phosphate uridyl transferase enzyme which is caused by mutations in GALT gene coding for GALT enzyme. This results in the accumulation of toxic derivatives of galactose.
- Newborns asymptomatic at birth
- Days later ➔ loss of appetite, vomiting, diarrhea
- Progresses to extreme weight loss
What should patients with GALT deficiency avoid in their diets?
Lactose and galactose
What are the liver forms and skeletal forms of GSD? What are the symptoms of GSD?
Liver - hepatomegaly and hypoglycemia
Skeletal - exercise intolerance
Symptoms
1. Hypoglycemia
2. Decreased insulin
3. Increased glucagon
What do disaccharidase deficiencies lead to?
What are the symptoms?
Carbohydrate malabsorption and intolerance
Diarrhea, abdominal pain and distension, flatulence
