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What are starches?
- Glucose polymers
- Amylose is a glucose in alpha linked chains
- Amylopectin is alpha linked glucose chains but has branches with alpha 1-6C linkages (which we cant digest)
What is insoluble fibre?
- Adds bulk
- Delays gastric emptying, leading to a fuller feeling with less intake
- Binds to cations
- Provides some glycemic control by inhibiting the uptake of other nutrients
- Some fermentation by colonic bacteria, but is a laxative mostly by bulk effect
What is soluble fibre?
- Forms a viscous gel
- Delayts gastric emptying
- Binds to cholesteorl and bile acids
- Fermented by colonic bacteria
Where are CHO absorbed?
Carboydrates are absorbed in the intestine by enterocytes of the villi in GI tract
How are carbohydrates digested in the mouth?
What enzymes help CHO digestion in the lumen?
- pancreatic amylase
How is lactose intolerance diagnosed?
What is lactose intolerance?
When lactose is not digested properly and ends up in the colon
What is primary lactast non-persistence?
- Stop producing lactase as you age
- 70% of population worldwide has this type of lactose intolerance
- Some asian populations have higher incidence, soe african tribes have much better lactose tolerance
- Caused by mutations to the lactase enzme coding gene (autosomal recessive)
What is seconday lactose intolerence?
Due to parasitic infection or malnutrition
What is congenital lactase non-persistence?
- Rare; born without ability to synthesize the functional protein
- Infants with congential lactase non-persistence require lactose-free formula
How is glucose absorbed?
- Glucose absorption is through the enterocytes Na+/glucose cotransporter at the apical surface in the lumen of small intestine
- Na+ flows from area of high concentration to low concnetration and the glucose channel along its gradient
- Na+/K+ ATPase keeps the intracellular Na+ concentration low
What is GLUT1?
- Placenta, brain, kidney, colon
- Part of the blood-brain barrier
- Not highly expressed in muscle of liver
- Asymmetrical affinity for gluycose allows for effective transport even when the extracellular glucose concentration is low and transport into the cell is required
What is GLUT2?
- Liver, B-cell, kidney and small intestine
- Symmetric flow
- High capacity, low affinity for rapit efflux following gluconeogenesis
What is GLUT3?
- Brain, neurons
- Relatively low glucose affinity
- Present in spermatozoa because there is glucolysis in the genital tract and the spermatozoa take up glucose from the epidymal fluid
What is GLUT4?
- Muscle, heart, fat
- Insulin resposive
- Present in intracellular vesicles until insulin stimulates their delivery to the plasma membrane
What is GLUT5?
- Small intestine, spermatozoa
- Acts as a fructose transporter
What is the normal circulating blood gluose?
What are the symptoms of hypoglycemia?
- Not enough glucose to fuel the brain
- Confusion, disorientation, drunk appearance
What are the symptoms of hyperglycemia?
- Can lead to diabetic coma
- Happens in surgery and intensive gare
- Leads to increased incidences of infection, increased risk of death
What happens to glucose once it is absorbed?
Once absorbed from from the small intestine, glucose and other monosaccharides are transported to the liver by the bloodstream
What happens to glucose when it enters the liver?
Glucose entering the liver is phosphorylated by glucokinase
What happens to glucose in peripheral tissue?
In peripheral tissue, glucose is phosphorylated by hexokinase
Why does not much glucose end up in the liver after a meal?
Hexokinase has a higher affinity for glucose than glucokiase, so when there is a high blood glucose concentration after a meal, more glucose is taken up for immediate use in tissues than is taken up by the liver as glycogen
What is glycemic index?
Glycemic index is a measure of the amount of glucose available in the plama over time generally compared to a standard of white bread
What is glycemic load?
(glycemic index)*(grams of carb/portion)
How does the pancreas get sugar?
- The pancreas gets its sugar through GLUT2 receptors that are non-insulin dependent
- This glucose undergoes glycolysis, ATP is synthesized
- K+ is pumped into the cell as ATP is pumped out, depolarizing the cell, allowing the release of stored insulin
What is preproinsulin?
Preproinsulin is a long protein with singnal sequence that is cleaved
What is proinsulin?
Has A, B, and C chains
What is active insulin?
Has A and B chains seperate but held together by sulphite bonds
What regulates glucose concentration?
Glucose concentration is regulted by insulin, glucagon, epinephrine, thyroid hormone, glucocoticoids, growth hormone and adipopectin
Where does is insulin secreted from?
Insulin is secreted by beta cells in the islets of Landrhans in the endocrine pancreas
What happens if glucose levels are too high in T1DM?
If glucose level in the blood is high it is filtered out by the glomerulus in the kidney and isnt reabsorbed into the renal tubules --> excreted
What is ketoacidosis?
- Present in T1DM
- Production of ketone bodies as a side product of the beta oxidation of fatty acids in the absence of glucose
How is insulin resistance quantified?
Insulin resistance is quantified by insulin lamp experiment
What are the three ways of insulin clamp experiment?
- Glucose infusion
- Insulin infusion
- Amino Acid infusion
What is glucose infusion?
- A hyperglycemic platau is achieved and maintained by a glucose infusion
- The rate of infusion that is needed to maintain that gucose level is equal to the rate of glucose metabolism
- There is an intial burst of insulin then steadily increasing release
How does insulin infusion work?
- Maintain a high level of insulin and slowly infuse glucose
- The level of glucose that is infused is the level that is being taken up into cells
What is the point of creatine in muscles?
- Creatine is present in muscle as creating phosphate which is hydrolyzed to make creatin and ATP
- Short term energy supply increasing power but probably not endurance, probably increases lean muscle mass
- Synthesized in the kidney and transferred to liver
- Creatinine waste product is excreted to urine, its measurement can be used to assess muscle mass
What is the main component of the urea cycle?
What happens if you do not have amino acid homeostasis?
- Having no homeostasis can mean no growth, mental retardation
- Children need more synthesis than breakdown
How does one measure the production of arginine in humans?
To determine the minimym production of arginine in humans one can measure the urea as they are in a 1:1 ratio
Why do infants have a higher requirement for proteins?
- They have a higher turnover
- They need 175umol/kg/day
What are the benefits of glutamate supplements?
Less infection, more gut absorption, increased survival, better N balance, ewer days on ventilator and parenteral nutrition
Why is glutamine added to perenteral nutrition?
- Will lead to the retention of lean body mass by reducing protein breakdown, promote growth and speed return to real food
- Glutamine supplemetation reduced proteolysis by 23%, reduced synthesis by 13% and improved net protein balance by 100%
What is hemoglobin?
- Specialized to cary oxygen
- Tetramer of two alpha and two beta chains
- Heme is the critical non-protein component that holds the iron atom at the cnetre
What is used to express intracellular glucose concentration?
Irriversible binding of Hb and glucose--> HbAic is used to express intracellular glucose concentration
What is erythropoiesis?
- Decrease in oxygen supply stimulates the making of new RBC by kidney
- Kidney senses change, releases erythripoietin that causes release of proerythroblasts in bone marrow--> early, intermediate, late erythroblasts-->reticulocytes-->blood-->mature RBC-->increase in oxygen supply
- Erythropoietin used for blood doping
How is heme biosynthesized?
- Succinyl CoA + glycine --> (vit Bg dependent enzyme) --> aminolevulinate (rate limiting step)
- (PGB synthase)--> UPC-->protoporphyrin (iron in)-->(heme synthase)-->heme
Where does heme synthesis happen?
Aminolevulinate synthase is in the mitochondria, but the rest happens in the cytoplasm
What are porphyria?
Diseases of heme biosynthesis
What is acute intermittent porphyria?
- Error with UPG III synthase
- No skin disturbances but potential neurological disturbances
- Need high carb diet and heme injections to decrease aminolevulinate
What is porphyria ccutanea tarda?
- UPG decarboxylase
- Hyperpigmentation/blistering of the skin
- Need to move to cloudy areas and have phlebotomies
How is heme synthesis regulated?
Negative feedback by heme
How is heme degraded?
- Removal of iron in the liver or spleen (Fe then bound to ferritin to be recycled)
- Hem is then broken down into billiverdin-->bilirubin (bile)
- Some bile wil be reabsorbed as urobilinogen, some will end up in urine
What is the functional form of iron?
Iron has to be bound to protein in Fe3+ functional form but it is consumed as Fe2+ in diet
Why is Fe2+ bad?
Fe2+ free is a dangerous oxidant leading to the fenton reaction
What is jaundice?
Accumulation of bilirubin in the blood
What are the three types of jaundice?
Pre-hepatic, hepatic, post-heptic
What is pre-hepatic jaundice?
Increased RBC degredation
What is hepatic jaundice?
Bile formation (liver disease) decreased ability to metabolize and excrete bilirubin
What is post-hepatic jaundice?
Bile removal issue, pale feces, dark urine
How is neonate jaundice treated?
Need UV light to increase destruction of billirubin
What is rhabdomyolysis?
- Result of statin therapy for high cholesterol
- Massive muscle breakdown (results in pain)
- Myoglobin is released, blood in urine shows acute renal failure
- Leads to incrase in potassium levels (hyperkalemia) that cause heart rhythm side effects
- Muscle necrosis
What is the most common cause of anemia?
- Deficiency of iron is the most common cause of anemia
- Causes defective hematopoiesis
- Decreased transport and decreased ferritin saturation
- Decreased stores of ferritin
Why cant we fortify food with iron?
Men are already eating excess, dont want to lead to hemochromatosis
What is marasmus?
- Severe deprivation/malabsorption of protein, energy, vitamins and minerals
- Develops slowly
- Severe weight loss and muscle wasting including cardiac muscle
- Children will weight <60% for their age
- Anxiety/apathy, skin and bones, possible good appetite
What is kwashiorkor?
- Older kids than marasmus
- Inadequate protein and energy intake
- More rapid onset
- Complicated by infections, edema and fatty liver
- Some fat/muscle retention despite starvation
- Treatment is more complicated due to fluid/electrolyte imbalance
What is GIN therapy?
Glucose and insulin administration while maintaining normoglycemia
How do histones regulate gene expression?
Histones regulate transcription (and therefor gene expression) by controlling the degree of condensation of the DNA