DLA 16 and Lecture 27+28 Flashcards
digestion in the mouth
carbohydrate digestion by salivary alpha amylase
this enzyme cleaves alpha 1,4 bonds of starch and glycogen and forms branched oligosaccharides
lingual lipase for lipid digestion
released in the mouth but mainly swallowed
digestion in the stomach
gastrin
leads to HCl release from parietal cells
release of pepsinogen and gastric lipase from chief cells.
role of HCl in the stomach
HCl denatures food; leads to quicker digestion
destroys fungi and bacteria
alters the conformation of pepsinogen to pepsin; autocatalytic activation
pepsin cleaves peptide bonds within the protein (endopeptidase)
acidic chyme in the stomach
stops carb digestion… salivary amylase is denatured
protein digestion starts from pepsin
breakdown of TAGs
role of secretin and CCK
when the acidic chyme reaches the duodenum, these enzymes are released to assist with neutralizing the pH
role of CCK and digestion
release of bile from gallbladder
activation of enteropeptidase enzyme
secretion of pancreatic enzymes
inhibition of gastric motility; allows pH change
role of enteropeptidase
activates zymogens:
trypsinogen to trypsin
chymotrypsinogen to chymotrypsin
proelastase to elastase
procarboxypeptidases to carboxypeptidases
for lipids:
prophospholipase A2 to phospholipase A2
procolipase to colipase
lactose intolerance
pain, nausea, flatulence, and diarrhea after the consumption of lactose
suppose to be broken down by lactase
lactase synthesis
The LCT gene for lactase is generally less expressed after infancy (lactase non-persistence phenotype)
The gene expression is controlled by MCM6
inherited changes to this leads to prolonged synthesis of lactase (lactase persistence phenotype)
abnormal lactose metabolism
lactase deficiency will lead to lactose reaching the large intestine.
the gut bacteria degrade the lactose to osmotically active compounds and thus lead to symptoms
osmotic diarrhea- water entering the lumen from cells
treatment of lactose intolerance
diet low in lactose
lactose free products
lactase pill
forms of lactose intolerance
- lactase non-persistence or primary lactose intolerance
lactase is strongly reduced after age 7
adult hypolactasia
- disaccharide deficiency - secondary lactose intolerance
all disaccharides are affected, but lactase is the first activity lost
can occur due to food poisoning
rotavirus
celiac disease
- congenital lactase deficiency (most severe and most rare form )
symptoms as a baby
need lactose free formula
activation of trypsin
trypsinogen is released into the duodenum by the pancreas
activated when it reaches the lumen; due to it being a powerful enzyme
activated by enteropeptidase
once trypsin is activated what does this enzyme activate
chymotrypsin
elastase
carboxypeptidase
phospholipase A
colipase
where does trypsin cleave
after arginine or lysine
where does chymotrypsin cleave
after bulky and aromatic residues
where does elastase cleave
glycine, alanine, and serine
where does carboxypeptidase cleave
cleave from the carboxy-end
absorption of AA’s
done mainly by secondary active transport with the co-transport with Na
the release of AA’s into the portal vein is by facilitated diffusion
absorption of monosaccharides
dietary fructose enters the intestinal cell via facilitated transport via GLUT 5
dietary glucose and galactose will enter the intestinal cell via SGLT-1
secondary active transport with Na
all three monosaccharides are released via facilitated transport by GLUT-2 into the portal vein
function of bile salts?
- transportation of free cholesterol and conjugated bilirubin from the liver to duodenum
- emulsify dietary lipids for digestion
- form mixed micelles for the uptake of lipids into the mucosal cells
colipase action?
The protein colipase pushes bile salts away from TAGs and anchors pancreatic lipase to the lipid droplet.
pancreatic lipase function
cleaves TAGs only to MAG’s
Orlistat
a drug used to inhibit pancreatic lipase for weight loss treatment
end product of nucleic acids
uric acid that is released into the urine
possible causes of steatorrhea
- lack of conjugated bile salts due to liver damage, bile duct obstruction, and/or pancreatic tumor
- defects related to pancreatic secretions
deficiency in enzymes - defective intestinal cells or shortened bowl
what reactions require BH4 as a cofactor
phenylalanine hydroxylase (Phe to Tyr)
tyrosine hydroxylase (Tyr to DOPA)
tryptophan hydroxylase (Trp to 5-hydroxy tryptophan)
PKU II or malignant PKU
deficiency of BH2 or dihydrobiopterin reductase
much more severe CNS symptoms:
decreased neurotransmitter synthesis (serotonin, dopamine, Epi, and Norepi)
treatment includes Phe diet restriction and providing dietary biopterin
treatment can also be saproterin or an analogue of BH4
biochemical defect of PKU II
No BH2 and/or no dihydrobiopterin reductase
deceased melanin synthesis and decreased neurotransmitter synthesis
tyrosine becomes essential AA
increase in phenylpyruvic acid
Tetrahydrobiopterin deficiency
results in hyperphenylalaninemia and decrease synthesis of neurotransmitters
results in intellectual disability and seizures
management:
provisional neurotransmitters
dietary restriction of phe
S-adenosyl methionine (SAM)
synthesized from methionine
A methyl group donor in many reactions
after the donation of the methyl group SAM is converted to homocysteine
homocysteine may be converted to cysteine by transsulfuation pathway (need PLP or B6)
or
conversion back to methionine by B12 and methylfolate
importance of 1-carbon pool
products formed are purines and pyrimidines
required for DNA and RNA synthesis (cell division)
folate deficiency
reduction in 1-C donors, thus reduced synthesis of purines and pyrimidines
delay in DNA synthesis, thus reduced rates of cell division
effects on RBC formation- see macrocytes and megaloblasts
decrease in hemoglobin concentration
polysegmented neutrophils
who is at risk for folate deficiency?
those who are pregnant (neural tube defects)
chronic alcohol consumption
those who do not eat vegetables (green, leafy)
histamine load test????
used to determine folate deficiency
in folate deficiency, it is seen that histamine metabolism is limited and FIGLU accumulates
more FIGLU in the urine
Vitamin B12 deficiency
macrocytic anemia and neurological features
(tingling in hands/feet, inability to walk, psychiatric, and urinary incontinence)
usually absorbed in the terminal ileum with intrinsic factor (released by parietal cells)
have increased levels of methylmalonate in circulation and in urine
elevated homocysteine levels
have normal levels of un-usable folate (methyl THF form)
functions of B12
animal sources are rich in vitamin B12
needed for methionine synthase
needed for methylmalonyl CoA mutase
reactions that need B12?
conversion of homocysteine into methionine via methionine synthase
conversion of methylmalonyl CoA to succinyl CoA via methylmalonyl CoA mutase
folate trap
when one does not have correct levels of vitamin B12
the cellular folate is stuck in the methyl-THF form
cannot be converted back bc the reaction is not reversible
who is at risk for B12 deficiency
Vit. B12 is stored in the liver, so it takes some time to develop a lack of B12
usually seen in vegans or failure to absorb B12 due to
atrophic gastritis
pernicious anemia
disease of the ileum
diff between folate and B12 deficiency
In vitamin B12 deficiency one will see neurological manifestations and an increase in methylmalonate
