DLA 11 + lecture 15+16 Flashcards
source of NADPH for fatty acid synthesis?
- PPP
- malic enzyme
NADPH is needed for FA synthesis
citrate lyase
uses citrate to form acetyl Co-A and oxaloacetate in the cytosol
mechanism of FA synthesis
- formation of malonyl CoA by acetyl CoA carboxylase
- synthesis of palmitate by FAS
- elongation of palmitate by elongases
- desaturation by desaturases
rate limiting step of FA synthesis
ACC or acetyl Co-A carboxylase
contains biotin
requires 1 ATP
FAS is regulated by….
insulin upregulates the amount of enzyme present
key intermediate between fat and carbohydrate metabolism?
acetyl Co-A
activator and inhibitor of FA synthesis
activator: citrate
inhibitor: long-chain fatty acyl CoA (inhibits acetyl CoA carboxylase)
activator of hepatic synthesis of FA’s and cholesterol?
insulin!!
what pathways does insulin favor?
glycolysis
glycogen synthesis
fatty acid synthesis
cholesterol synthesis
where does FA chain elongation occur?
ER by elongases
fatty acid desaturation system?
desaturases introduce double bonds at positions 5,6, or 9 in humans
is an electron transport system in the ER
involves cytochrome b5 desaturase and NADPH cytochrome b5 reductase
double bonds beyond position 9 are essential fatty acids
dietary essential fatty acids
linoleate and alpha linolenate
how is acetyl CoA carboxylase regulated
allosteric:
activated by citrate and inhibited by palmitoyl CoA
covalent:
activated by dephosphorylation
inhibited by phosphorylation
enzyme:
activated by insulin
polymer is inactive and protomer is inactive
short term allosteric regulation of FA synthesis
citrate shifts toward polymer formation using protomers (activation)
palmitoyl CoA shifts toward protomers formation by depolymerization (inhibitor)
Role of AMP activated protein kinase (AMPK)
how is AMPK activated?
acetyl CoA carboxylase is inhibited when phosphorylated by this enzyme
activated:
allosterically by AMP
covalent by phosphorylation (glucagon, epi, and norepi trigger phosphorylation)
Role of CPT I?
malonyl CoA which is formed in the cytosol during FA synthesis inhibits CPT I
CPT I: moves long chain fatty acids into the mito for beta oxidation
this ensures that during FA synthesis, beta oxidation is inhibited
histology of the gastro-duodenal junction
mucosa:
appearance of finger-shaped villi
submucosa:
appearance of Brunner’s glands for mucus
muscle:
2 typical layers of muscle.. no oblique layer
peptic ulcers
crater-like lesion in areas exposed to gastric juices
common cause: infection by H. Pylori (breaks down mucus and creates alkaline environment; leads to more acid production) smoking NSAID zollinger-Ellison syndrome: gastrinoma
loss of mucosal protection and thus inflammation
complication of chronic peptic ulceration
ulcers may extend deeper if left untreated
can lead to bleeding, perforation, peritonitis, pernicious anemia
mucosa and submucosa of the small intestine?
mucosa: simple columnar contains GALT 2 muscular layers have villi have crypts of lieberkuhn
submucosa:
DCT
contains Meissner’s plexus
circular folds of plicae circularis
crypts of lieberkuhn (SI)
invagination of epithelium into the LP
simple columnar epithelium
simple tubular glands
enterocytes (SI)
simple columnar cells for absorption
can produce digestive enzymes and secrete water
goblet cells (SI)
unicellular mucus secreting cells
increase in number from small intestine to large intestine
Paneth cells
found at the base of intestinal glands
secrete lysozyme: antibacterial enzyme and digests certain bacteria
Alpha defensins: microbicidal peptides
regulates normal bacterial flora of the small intestine
enteroendocrine cells in SI
similar to those seen in stomach
found at the base of the crypts
releases CCK, secretin, GIP, Motilin
(peptide hormones)
M cells in the SI
ATC cells in SI
M cells:
epithelial cells that cover peyer’s patches and large lymphatic nodes
ATC:
take up microorgansims and macromolecules from lumen
distinguishing characteristic of the duodenum?
The presents of Brunner glands
these glands secrete an alkaline mucus that neutralizes acidic chime
distinguishing characteristics of the jejunum
plicae circularis- have a feathery appearance
long prominent villi
distinguishing features of the ileum
absorption of vitamin B12 occurs here
increase in paneth and goblet cells
lumen is smaller
has peyer’s patches
celiac disease
gluten sensitivity
autoimmune mediated intolerance to gliadin
inflammation in distal duodenum and proximal jejunum
mucosa will appear flattened due to atrophy of villi and hyperplasia of crypts
Crohn’s disease
ulcer formation of mainly the SI (def the ileum)
malabsorption and crampy abdominal pain
cobblestone appearance due to inflammation
can see giant cells
can have fibrosis
distinguishing features of the large intestine
Taenia coli
haustra
omental appendices
Colonic Adenomatous Polyps - Adenomas
slow growing intraepithelial neoplasm
usually no symptoms; sometimes bleeding
three types:
tubular - most common; less likely to become cancer
villous - rare; fingerlike appearance
tubulovillous - intermediate features
three zones of the anal canal
- colorectal zone
upper 1/3; simple columnar - anal transitional zone
middle 1/3
transition between simple columnar to strat. squamous - squamous zone
lower 1/3
keratinized strat. squamous
