Secreted in response to the movement of gastric acid.
-stimulates the liver, pancreas, gastric and intestinal cells to secrete HCO3 and H2O
Breaks down plant starches and glycogen into Maltose, maltitriose, and alpha dextrins (limit-dextrins) in the mouth
Breaks down amylase, amylopectin, glycogen, and maltose into glucose
Breaks down alpha dextrins, sucrose, maltotriose, and maltose into glucose and fructose
Breaks down sugar from mushrooms, algae, fungi, and insects into glucose
Breaks down lactose and glycolipids into glucose and galactose
Sodium Dependent Transporters
-Membrane Protein transporter
-allows glucose and galactose and Na
-Found in Renal and Intestinal cells
Membrane Protein Transporter-absorbs Fructose only
(found in intestines, testes, brain, liver, kidneys)
Insulin Sensitive Membrane Protein Transporter
(found in adipose, skeletal muscle, heart, brain-neurons and astrocytes)
Membrane Protein Transporter for cell types with barrier functions. High Affinity Glucose
(most cells, human erythrocyte, BBB, BRB, BPB, BTB, Brain (astrocytes/glial))
Membrane Protein Transporter
-high capaciity, bidirectional . Transports Glucose, Galactose, and Fructose
(found in Liver, Kidneys, Pancreatic B-cell, Serosal Intestine mucosa cells)
Membrane Protein Transporter in the ER of liver
Membrane Protein Transporter-newly discovered
(found in brain-neurons, testes, adipose, muscle)
Major Membrane Protein Transporter in the CNS
Fructose will be linked to ___ in the fed state and __ in the fasting.
Galactose is used to produce:
What pathway is used to convert Galactose into Glucose in the liver and intestinal cells?
What enzymes are used?
Where are the highest concentrations of galactose found in a lab test?
-10 x more
-what is not metabolized in liver or intestine
In Classical Galactosemia, ______enzyme is deficient leading up to build up of _____ and _____.
(common in infants)
This Galactose metabolism disorder affecting mostly RBCs and WBCs from a deficiency of _______ enzyme.
Deficient ____enzyme will cause a buildup of Galactose in the blood.
What are some test results that confirm the diagnosis of Classical Galactosemia?
-Impaired liver function
-Elevated blood galactose levels
-Hyperchloremic metabolic acidosis
-Hyperaminoaciduria (high AA)
-High galacticol excretion in urine
-Increased Galactose-1-Phosphate inside RBCs
A buildup of Galactose caused by Galactokinase Deficiency can cause _____.
-fail to develop social smile
-fail to visually track moving objects
-same labs as others (look for enzyme in blood level)
How and why does Galactose get converted to Galactitol in neural tissue and lens of the eye?
-too much galactose in circulation
-Aldose Reductase (w/NADPH) converts to Galacticol
-cannot complete Polylol Pathway
What lab tests should be done to confirm galactose disorders in newborns?
-Blood test-from heel
-Urine-check for 3 enzymes:
2. Galacto-1-phosphate unidyltransferase
How to treat galactose disorders
-Eliminate lactose from diet
-Use Soy based formula
-Surgical removal of cataracts(only persistent ones)
Why is fructose used in gatorade?
-immediate source of energy
-active in both fed and fasting states
When does hexokinase convert fructose into fructo-6-phosphate to join glycolysis?
When there is not enough Glucose
-has higher affinity for Glucose
What cycle does fructose enter in the fasting state?
What enzyme is deficient in Fructose Intolerance?
-inhibits connection of fructose-1-phosphate to glycolysis
(in fed state)
How does fructose intolerance affect the fasting state?
It causes an accumulation of:
What is affected if phosphates are trapped?
-ATP, GTP synthesis
-glyconeogenesis, glycolysis, glycogenolysis
-leads to cell death
How will blood tests confirm fructose intolerance
-Liver fxn panel fail
How do you treat fructose intolerance
-Elimination of Fructose and Sucrose from diet
-may not prevent progressive liver disease
What is fructose malabsorption?
GLUT 5 in deficient
-fructose is digested by flora in gut
What do the flora produce after consumption of fructose?
-short chain FA
-H+, CH4, CO2
What is a consequence of fructose malabsorption?
-promotes bio-film in gut
-decreased tryptophan, folic acid,and zinc in blood
-decreased absorption of some nutrients
What lab tests are run to diagnose fructose malabsorption?
Hydrogen breath test(adults)
Stool acidity test (infants)
How will urine tests confirm fructose intolerance?
-Positive for reducing sugars (high levels of sugars)
What is fructosuria?
Deficiency of hepatic fructokinase
-cannot convert fructose to fructose-1-phosphate
-excess fructose excreted in urine
Where is glycogen stored?
Mainly in Liver and Muscle cells
What is the two unit subunit enzyme that initiates glycogen synthesis?
-free in fasting state-liver
What is the substrate for the active site of glycogenin?
-made from galactose
-converted from glucose
What is a glycogen primer?
8-12 glucose molecules attached to the glycogenin
-alpha 1,4 linkage
What enzyme transfers a glucose molecule from UDP-glucose to the terminal residue of a glycogen primer?
What enzyme breaks 5-8 glucose residues from the chain to make a branch?
(amylo (a-1-4, a1-6) transglycosylase
The globular structure of glycogen contains how many concentric rings?
-@30k glucose units
What is an advantage of the ring structure?
-exposed carbon makes easy degradation/synthesis
In the fed state, what does insulin do?
-glucose to glycogen
-glucose to TG
-enzymes for carb metabolism
-inhibits glycogenolysis enzymes
What is a type 0 glycogen disorder?
-failure to thrive
What is a type 4 glycogen disorder?
-altered glycogen structure
What does the polyol pathway do?
converts glucose to sorbitol to fructose
What happens when there is too much sorbitol in the lens of the eye?
Why is sorbitol not converted to fructose to limit cell damage?
Sorbitol is produced faster than it can convert to fructose.
-cannot leave cell-toxic
-leads to cell lysis and loss of function
-peripheral tissue cells
-blood vessel cells
What tissue uses lactate for energy?
(provided from RBCs, seritoli cells, astrocytes,muscles)
Glycogenolysis is the breakdown of _____.
What enzyme starts the breakdown of glycogen by breaking the a-1,4 bonds
-pyridoxal (b6) cofactor
What product is initially made when glycogen is split?
Two glucose-1-phosphate molecules
What enzyme goes into effect during glycogenolysis when there are only four glucose molecules left on a branch?
(4:4 transferase), then
What enzyme converts G-1-P to G-6-P during the last stage of glycogenolysis?
Where do the G-6-P molecules end up after glycogenolysis?
-Pentose Phosphate Pathway
What three hormones regulate glycogenolysis in the liver?
Glucagon, cortisol, and epinephrine
-released due to hypoglycemia
-fasting, low carb diet, sleep, exercise
-stress on the body
What binds to B Receptors and magnifies the effect of Glucagon?
What is inactivated when glucagon enters the liver and muscle?
What is activated when glucagon enters the liver and muscle?
What hormone counters the effect of insulin and stimulates gluconeogenesis to increase blood sugar levels?
What is affected in Type 1 VonGlerke's glycogen disorder
-stops conversion to glucose
What is affected in Type III Cori's glycogen disorder?
-no free glucose
-altered glycogen structure
What is affected in Type V McArdle's glycogen disorder?
-no breaking of glycogen
What is affected in Type VI Hers' glycogen disorder?
-no glucose to brain
-breaks down AA/FA
What is lactogenesis and where does it occur?
production of Lactose
-mammary glands in females
-uses both glucose and galactose
What hormone stimulates lactogenesis?
-other hormones levels drop after childbirth leaving high levels of prolactin
-or suckling of infant
What enzyme converts UDP glucose to UDP galactose?
What enzymes are synthesized in response to prolactin and cortisol?
A-lactalbumin and galactosyltransferase
-increases production of lactose
What enzyme removes galactose from UDP galactose and bonds with glucose to create lactose?
-enhanced by A-lactalbumin
What is the first milk a breastfed baby receives?
What is special about it?
-high amounts of WBCs, and Antibodies
(more than mature milk)
What does IgA do for a newborn?
coats lining of intestines
-prevents food allergies
What is in mature breast milk?
What glucose/galactose pathway creates no ATP, makes macromolecules for other functions in the body,and connects to the pentose phosphate pathway?
Uronic Acid Pathway
-AKA Glucuronic Acid Pathway
What is the clinical significance of glucuronides?
eliminates insoluble(non polar) substances from body
-out in urine and bile
-facilitates transport of insoluble drugs in body
What is the synthesis of glucuronides called and where does it take place?
-mainly in liver
-other-H,K,spleen, adrenal glands, thymus
What enzyme catalyzes glucuronidation?
-AKA UDP glucuronyltransferase
Non polar substances that are transported by glucuronides
morphine, sleep drugs, cancer drugs
-Steroids,Thyroid hormones (T3 and T4)
-fatty acid derivatives
What compounds can help control the progression of cancer by increasing the rate of glucuronidation reactions?
- D-glucaric acid
-lung, skin, liver, breast, colon, bladder, and prostate cancer
How do the "anti-cancer" compounds work?
- inhibit the enzyme B-glucuronidase
- suppress cell proliferation and inflammation
How is 80% of Bilirubin produced?
Degradation of Hb in RBCs
-20%-myoglobin, cytochrome p450
How is Bilirubin transported in circulation?
-Bound to Albumin
-transported to liver
What happens to unconjugated Bilirubin in the liver?
-makes conjugated Bilirubin
Where does conjugated bilirubin go after the liver?
-most to intestines
-some in plasma-to urine
What do intestinal bacteria do with conjugated bilirubin?
-90% converted to stercobilin/urobilin
-color of poo
What enzymes convert Heme to bilirubin?
Microsomal heme oxygenase
-biliverdin + Fe
-Fe stored as Ferritin
What is Jaundice or Icterus?
Excess unconjugated, conjugated, or urobilinogen in circulation or urine
What are the causes of Jaundice
-Too much unconjugated bilirubin-liver cannot conjugate all
-Hepatic disease-liver can't conjugate
-Liver disease-cannot reabsorb or re-excrete urobilinogen
-duct obstruction-backup of conjugated bilirubin
-over-abundance of u-b in blood
-increase urine urobilinogen
-increase fecal urobilinogen
-normal AST, ALT, ALP
-no urine bilirubin
-Increase AST and ALT
-Increase urine urobilirubin
-urine bilirubin present (dark)
-decrease fecal urobilirubin
Intrahepatic (Neonatal) <30 days old
Immature liver cells
-no Urine urobilinogen
-no fecal urobilinogen
Post Hepatic Jaundice (obstructive)
-urine bilirubin present (dark)
-no fecal urobilinogen (blocked)
-no urine urobilinogen
-normal AST, ALT
Causes and signs of liver disease
hepatitis exposure, transfusions, IV drug use, alcohol use, some meds, or family history
-blood test will specify
How to treat jaundice caused by sickle cell anemia
-increase iron in diet or supplements
Tests to run to diagnose Jaundice
-plasma bilirubin-conjugated and total
-Liver Panel-AST, ALT, ALP, GGT
-measurement of coagulation time (PT)
What disease is marked by a unconjugated bilirubin level that rarely exceeds 50?
-enzyme for conjugation
Causes of Intra-hepatic Jaundice in Newborns
-Immature Liver Cells-can't conjugate or might leak into intestine
-unconjugation in intestine by B-glucuronidase -re-enters bloodstream
-RBC destruction - maternal IgG problems or conversion to adult Hb
What is the most common type of neonatal jaundice?
What is the most severe form of Jaundice in newborns?
serum>300 of U-B
-no C-B in urine
-U-B and no uribilinogen in Meconium
What are some causes of post-hepatic obstructive jaundice?
-Cancer-mass closes lumen
-Gall Stones (>60yrs)
Possible treatments for neonatal jaundice
-takes care of skin color
IVIG-due to blood group incapatabilities
-exchange transfer of blood
How are gall stones treated?
Surgically by removing gall bladder