Midterm 1 Flashcards
Functions of saliva
Moistens food, glycoproteins lubricate/prevent abrasion, digestion of starch, antimicrobial agents
Submucosa
support layer under mucosa, has blood vessels and nerves
Muscularis
circular and longitudinal muscles (in all of tract except stomach)
Serosa
lubricated covering, holds organs in place
Cardia
first portion of stomach
Fundus
outer layer of stomach
Body
main part of stomach
longitudinal, circular and oblique layers
Muscularis in stomach
Rugae
folds that allow stomach to expand
Functions of stomach (6)
form chyme, store food, secrete acid, pepsinogen & mucus, initiate protein/lipid digestion, kill bacteria, absorb a few compounds such as alcohol
Gastric juice consists of:
HCl and intrinsic factor, pepsinogen and gastric lipase, mucus, water, electrolytes, bicarbonate
Chief cells
Secrete pepsinogen and gastric lipase
Parietal cells
Secrete HCl (and intrinsic factor)
ECL cell
releases histamine which binds to H2 receptor (on parietal cell) and increases acidification of the stomach
Acetylcholine
secreted by vagus nerve, acts upon M (muscarinic) receptor on ECL cell to promote histamine release or to M receptor on parietal cell to promote HCl release
Gastrin
Causes increased production of HCl by binding to CCK2 receptor on ECL cell or to G receptor on parietal cell directly
Histamine synthesis
histidine decarboxylase (plus Vit B6) converts histidine to histamine
Somatostatin
inhibits HCl production, produced by D cells in stomach, duodenum, pancreas
G cells
secrete gastrin, which bind to CCK2 receptor and increase activity of HDC which generates histamine in the ECL cell
D cells
secrete somatostatin
Goblet
secrete mucin (lubricant and buffer)
HCL production in parietal cells
ECL cells secrete histamine which promotes HCl secretion by binding to H2 receptor on parietal cells (Gastrin can bind to ECL cells as can acetylcholine (M receptor) or both can stimulate parietal cells directly)
Antacids
neutralizes HCl itself, (alka-seltzer, pepto-bismol)
Proton pump inhibitor
(prilosec) inhibits the proton pump
H2 blocker
Zantac, Pepcid, etc. Prevents histamine signaling
factors that influence rate of gastric emptying
composition of duodenal chyme, size of food particles (less than 2mm) and gut peptides (usually takes 2-4 hours)
Composition of chyme effects on gastric emptying
water & fructose have unregulated passage, whereas fatty acids/glucose/peptides have regulated passage –> constant energy to duodenum
cephalic phase
vagus nerve stimulates secretion, gastrin stimulates secretion by parietal and ECL cells
gastric phase
distention of stomach increases stomach secretions
intestinal phase
chyme enters duodenum which causes hormones that inhibit gastric secretions
functions of small intestine (4)
main site of nutrient digestion and absorption: digest food components, package lipids so they can be absorbed, absorb macro and micronutrients, barrier
villi, microvilli and brush border adds how much surface area
600x greater surface area (200 m3)
enterocyte
absorptive epithelial cells
endocrine cells in SI
secrete secretin, somatostatin, CCK etc
paneth cells
in small intestine, secrete lysozyme and antimicrobial peptides
Absorbed in duodenum and jejunum
Carbs, lipids, amino acids, calcium, iron
Absorbed in ileum
Bile salts, vitamin B12, water, electrolytes
Gastroileal reflex
When there is a lot of activity in stomach it will increase flow through small intestine (increase ileal activity)
Ileogastric reflex
Distention of ileum decreases gastric motility
Intestino-intestinal reflex
overextension of any segment relaxes other segments
Liver and gall bladder
secrete and hold bile
Liver functions
production of bile, detoxification, synthesis, secretion & storage of glucose, production of proteins
Portal triad and functions
Hepatic portal vein (small intestine liver, allows hepatocytes to absorb glucose); hepatic artery (heart –> liver, rich in oxygen); bile canaliculi –> bile ductule to common bile duct (takes bile made by hepatocytes to small intestine)
enterohepatic circulation
Bile salts travel from liver to the bile, into the small intestine, then absorbed and bile salts travel back to the liver through the portal vein (4 grams that cycle through SI 12x per day)
Acinar cells
secrete pancreatic lipase, amylase, trypsin (exocrine)
Beta cells
secrete insulin
Alpha cells
secrete glucagon
Exocrine functions of the pancreas
bicarbonate, trypsin and chymotrypsin (protein breakdown), pancreatic amylase, pancreatic lipase (pancreatic juice)
Endocrine functions of the pancreas
Insulin and glucagon
Functions of large intestine (3)
Absorb water, microbial fermentation, and formation and storage of feces
Differences of large intestine compared to SI (4 differences)
No microvilli, absorption limited to salts, water, some vitamins, no secretion of digestive enzymes, site of microbial fermentation
Water in GI tract
3L from intake, 15L from secretion…. 15L absorbed in small intestine, 3L enters colon, 2.8 reabsorbed, 0.2 in feces
Bulk lumen phase
First barrier - volume of lumen is barrier bc nutrients need to come into contact with the enterocytes – overcome by mixing
Unstirred water layer
2nd barrier - thin layer of water that interacts with proteins and glycans to form shell – polar molecules can diffuse through, barrier to TAG which must be packaged in micelles
Crossing apical membrane
3rd barrier - impermeable to large, charged molecules – mechanisms include osmosis, simple diffusion, facilitated diffusion, primary/secondary active transport
transcellular
transport across membrane
paracellular
cross between tight junctions (semipermeable, adhesion of cells)
Crossing cytoplasm
4th barrier - small molecules can diffuse, cytoskeleton provides directed transport
crossing basolateral membrane
5th barrier - similar to apical
Interstitial fluid
6th barrier - water soluble compounds diffusion, lipophilic things must be packaged into micelles
transport into blood vessels/lymph
7th barrier - water-soluble compounds diffuse into blood vessels, lipid-soluble enter via fenestrations
Clathrin
forms vesicle coating
Actin cytoskeleton
propels and elongates the clathrin coated pit
dynamin
encircles clathrin pit and pinches off vesicle (ATP dependent)
Aldose
carbonyl group at the end of the sugar
Ketose
hydroxyl group (CH2OH) at the end of the sugar (carbonyl anywhere but the end)
Bonds between sugars
glycosidic bonds
Schiff base
unstable intermediate produced by reaction of aldose and amines
Amadori product
ketoamine produced from irreversible non enzymatic glycation of schiff base, which produce tastes and aromas in food, browning, may reduce nutritional quality of the protein
Maillard reaction
aldose and amine –> schiff base –> amadori product
glycation
covalent bonding of sugar molecule to a protein (non enzymatic)
functions of carbohydrates (~3)
provide energy - 50% of energy and glucose is essential, prevent protein breakdown, prevent ketosis
starch (2 types)
amylose (alpha 1,4 linked) and amylopectin (a1,4 linked with a1,6 branches) —note that glycogen is more extensively branched
amylose
more resistant to digestion, tightly packed linear structures, hydrogen bonding between molecules
carb digestion
begins in mouth, some in stomach, pancreatic amylase, starch digestion complete at the duodenal-jejunal junction
amylase
binds 5 glucoses and cleaves between 2nd and 3rd glucose (end up with maltose, maltotriose and alpha limit dextrins)
isomaltase
breaks down alpha-limit dextrins (also called alpha-limit dextrinase) - the alpha 1,6 bonds
glucoamylase
breaks down alpha-limit dextrins - the alpha 1,4 bonds (or maltase will)
brush border enzyme trafficking
synthesis in ribosomes of ER –> golgi for additional glycosylation –> transport vesicle to the apical membrane
SGLT1
secondary active transport, sodium coupled glucose transporters, a symporter- both moving to inside of the cell (2:1) … high substrate affinity/low capacity… rapidly becomes saturated
GLUT2
facilitated diffusion of glucose - mainly basolateral membrane though trafficked to apical under high sugar conditions, low substrate affinity/high capacity
GLUT5
facilitated diffusion of fructose - mainly apical membrane, low substrate affinity/high capacity
SNARE proteins
allow docking of vesicle and fusion with membrane (exocytosis)
constitutive secretion
unregulated secretion/membrane fusion
regulated secretion
secretory vesicles are released in response to signals such as hormone or neurotransmitter
osmolality
units of osmotic pressure (moles of solute per L) or the force required to prevent osmosis
hypotonic meal
low sugar/solute meal causes water to move from gut into plasma… osm lumen
hypertonic meal
high sugar/solute meal causes water to leave blood and move into gut (lumen > plasma) ..can cause distension and dehydration
characteristics of facilitated diffusion (3)
specificity, competition and saturability
intraluminal glucose
increases mRNA for SGLT1 & GLUT2, trafficking of GLUT2 to apical membrane
intraluminal fructose
increases mRNA for GLUT5
CCK
stimulates bile and pancreatic lipase secretion
Arachidonic acid
used to synthesize eicosanoids
chylomicron
TAGs and apoB are packaged to leave enterocyte
NPC1L1
takes up cholesterol in enterocytes
CD36
takes up fatty acids in enterocytes
Acyl coA synthetase
activates fatty acids for re-esterification within the enterocyte
secretin
stimulates release of bicarbonate in response to low pH in the duodenum
gastric lipase
high affinity for medium chain fatty acids at sn3 position, breaks down 10-25% of all TAG
pro-colipase
secreted by pancreas, activated in intestinal lumen by trypsin – colipase helps pancreatic lipase function
fiber and cholesterol levels
- fiber may bind bile salts, 2. interference with lipids getting broken down by enzymes 3. fermentation in colon produces short chain fatty acids which inhibit cholesterol synthesis
TAG breaks down into
2-MAG and FFA
phospholipids break down into
lysophospholipid and FFA
Phospholipase A2
secreted by acinar cells in pancreas, breaks down phospholipids
cholesterol ester breaks down into
cholesterol and FFA
carboxylester lipase
breaks down chol. esters, secreted by acinar cells
synthesis of arachidonic acid
linoleic acid (omega 6) –> desaturation, add 2 carbons, desaturation –> arachidonic acid
H+ transport from parietal cell
primary active transport
Cl- into parietal cell
secondary active transport (bicarbonate out, down gradient and Cl- in up its gradient)
Cl- transport from parietal cell into stomach
facilitated diffusion (down its gradient)
ezetimibe
knockout of NPC1L1 to reduce chol. absorption
ABCG5/8
apical membrane cholesterol transporters, use ATP, transport plant sterols back
ABCA1
basolateral membrane cholesterol tranporters
FABP
fatty acid binding proteins –> maintain gradient for FFA, are responsible for binding and transporting fatty acids to the ER
Abetalipoproteinemia
mutations in MTP - microsomal TG transfer protein - unable to form chylomicrons
sitosterolemia
mutations in ABCG5/8 - build up of cholesterol/plant sterols
end up in chylomicrons
TAG, phosphotidylcholine, cholesteryl esters
what ends up in portal vein (from lipids)
short chain fatty acids, medium chain fatty acids and glycerol
Vmax of glucose transporters
SGLT1 much lower than GLUT2
low sugar meal (transporters)
SGLT1 on apical membrane –> GLUT2 basolateral
high sugar meal (transporters)
GLUT2 apical –> GLUT2 basolateral
hydrolysis of alpha limit dextrins starts at the:
non-reducing end
High plasma insulin upregulates:
1) glucose uptake by cells, 2) glucose metabolism and 3) glycogen/protein synthesis (to move glucose of the blood)
High plasma insulin downregulates:
1) gluconeogenesis, 2) glycogen breakdown, 3) lipolysis in adipose tissue (to reduce glucose entry into blood)
Insulin regulates enzymes by
dephosphorylating
PFK-2
converts fructose-6-P to fructose-2,6-BP (which is an allosteric activator of PFK-1); activated by insulin, inhibited by glycogen
Pyruvate kinase
converts PEP to pyruvate, activated by insulin, found in liver
Glycogen synthase
converts glucose-1-P to glycogen, activated by insulin
Glycogen phosphorylase
breaks glycogen down, INACTIVATED by insulin
PFK-1
Converts fructose-6-P to fructose-1,6-P
Net energy yield from anaerobic metabolism (glycolysis)
(8 - (6 to convert pyruvate into lactate)) = Net of +2 ATP
Net energy yield from aerobic metabolism (TCA cycle)
Net of +38 ATP
PDH (Pyruvate dehydrogenase)
negative delta G rxn (spontaneous), converts pyruvate to acetyl CoA
Citrate synthase
acetylCoA + oxaloacetate –> citrate, negative delta G rxn,
ICDH (isocitrate dehydrogenase)
isocitrate –> a-ketoglutarate + CO2; negative delta G rxn; maybe rate limiting step
KGDH (a-ketoglutarate dehydrogenase)
a-KG + CoA –> succinyl CoA + NADH; negative delta G rxn
Anaplerosis
act of replenishing TCA cycle intermediates that have been extracted for biosynthesis
High plasma glucagon regulates:
Upregulates 1) glycogen breakdown and 2) GNG … to move glucose into blood AND 3) downregulates glycogen synthesis and 4) upregulates ketogenesis to reduce glucose utilization
Glucagon & epinephrine (via cAMP)
reduce glycolysis and increase glycogenolysis
Iron is required for metabolic processes (3)
Oxygen transport & retention, DNA synthesis, and electron transport
Biological strategy to prevent iron toxicity
Constrain iron reactivity through association with proteins or prosthetic groups
Total body iron is divided into 3 groups
Functional iron (hemoglobin, myoglobin, enzymes) Storage iron (ferritin) and Transport iron (bound to transferrin)
Of the body’s 4 grams of iron:
2-3g are erythrocyte hemoglobin, also found in liver, spleen and muscle
Iron absorption is determined by 3 factors
1) iron content of the diet, 2) bioavailability of the dietary iron and 3) capacity of enterocytes to absorb the iron
Heme vs. non heme iron
more iron consumed is non-heme (Fe+2 and especially Fe+3) the majority of body iron is derived from heme iron
Factors that influence iron solubility and absorption (4)
1) pH (acidity increases absorption of non-heme) 2) Reduction of Fe+3 to Fe+2 (vit C does this) 3) solubilizing chelators (mucin, AA, sugars can form complex to retain solubility of Fe+3) 4) precipitating chelators (carbonates, oxalates can chelate Fe+3 reducing its solubility)
Where is iron absorbed?
in the duodenum, crypt cells sense iron, enterocytes absorb iron
DMT1
transports iron (& copper & zinc) Fe2+/H+ cotransporter, present on brush border of enterocytes
DcytB
reductase enzyme that catalyzes the reduction of Fe3+ to Fe2+, found in brush border
Heme oxygenase
once inside the enterocyte, this enzyme breaks down heme and releases iron, allowing it to move into intracellular iron pools — also in spleen, catalyzes the first step of degradation of heme: cleaves ring to form biliverdin and release iron
Intracellular iron pool
transient, low level pool of iron coming from broken down heme, diet intake, release from storage pools
Iron in the labile iron pool will be used in:
incorporation into cellular proteins, storage (ferritin) or export into circulation
ferritin (& 2 functions)
iron storage protein, 24 subunits shaped into a sphere, room for 4,500 iron ions. Ferritin is an iron reservoir and a means of safely storing Fe
Ferroportin
iron exporter (Fe2+ and Zn), integral basolateral membrane protein
Ceruloplasmin
converts ferrous iron into ferric iron (Fe2+ to Fe3+) and facilitates export by keeping levels of ferrous iron low
Hephaestin
converts ferrous iron into ferric iron (Fe2+ to Fe3+) and facilitates export by keeping levels of ferrous iron low
Transferrin
soluble protein that binds 2 ferric irons and transport them through the blood
%iron bound to transferrin
binds <1% of total body iron but high flux; normally transferrin is 30% saturated with iron (<16% indicates iron deficiency and >45% sign of iron overload)
Endocytic uptake of iron (5 steps)
1) Transferrin is bound by the transferrin receptor 2) Receptor-transferrin complex undergoes endocytosis 3) Acidification of the endosome triggers transferrin release of iron 4) Iron is transported into the cytoplasm 5) empty receptor and transferrin are recycled back to the outside of the cell and transferrin is released
IRE
Iron response element - present in the 5’ or 3’ of many mRNAs
IRP
IRE-binding protein, contains iron-sulfur cluster, in the absence of iron, IRP binds IRE’s
IRP binding impacts translation how:
binding a 5’ IRE prevents translation; binding a 3’ region increases mRNA stability
Proteins that have 5’ IRE
ferritin, ferroportin, ALA synthase (protein levels decrease when iron is low)
Protein with 3’ IRE
transferrin receptor (protein level increases when iron is low)
What happens when there is low iron (IREs)
iron is released from storage (less ferritin), iron is exported less (ferroportin) and heme synthesis is reduced (ALA synthase), uptake of iron into cells increases
What happens when there is high iron?
increased storage capacity, increased iron export, decreased uptake into cells to prevent toxicity
Hepcidin
controls plasma concentration of iron: reduces iron export by binding to ferroportin, inducing its degradation
Porphyrin
4 pyrole rings connected by methene bridges, heme has ferrous iron in the middle
ALA synthase (4 things)
performs first step of heme synthesis from glycine & succinyl CoA –> 5-ALA; irreversible, rate limiting step, requires PLP as a cofactor, occurs in mitochondria
ALA synthase regulation
has 5’ IRE, so low iron causes decreased protein translation, also heme inhibits transcription (negative feedback)
ALA dehydratase
combines 2 5-ALA to form porphoblinogen (PBG), inhibited by lead, occurs in cytosol
PBG deaminase
puts 4 PBGs together to form ring, in cytosol
UPG III synthase
removes water and completes the porphyrin ring
ferrochelatase
adds iron to finish heme molecule, in mitochondria, inhibited by lead
Major steps of heme synthesis
1) ALA synthase combines glycine and succinyl-CoA to form ALA. 2) ALA dehydratase uses zinc to condense 2 ALAs into PBG. 3) 4 PBGs combine. 4) Ring is completed. 5) Ferrochelatase adds iron to the heme
Heme synthesis occurs in all cells but especially in:
Bone marrow to make hemoglobin and in the liver for cytochromes
Biliverdin reductase
Enzyme that converts biliverdin to bilirubin
Bilirubin is transported to
the liver in a complex with albumin
UDP-gluc..transferase
converts bilirubin to bilirubin digluc which is the form excreted in the bile
Heme degradation occurs in:
spleen, blood and liver
Hematopoiesis
production of blood cells
Erythropoiesis
development, diff and maturation of erythrocytes (RBCs) … from stem cell there is decrease in size of cell and loss of mitotic activity, extrusion of organelles
Erythrocytes
No nucleus or organelles, high surface to volume ratio, ~120 day lifetime, withstand mechanical stress (270 million hemoglobin molecules)
Erythropoeitin
small glycoprotein cytokine, low blood [O2] stimulates erythropoietin release from kidney, erythropoietin stimulates bone marrow to make more RBCs
Ennucleation
extrusion of the nucleus from RBC
Heme degradation
RBC taken into macrophage and heme is broken down in to biliverdin –> bilirubin which is taken to the liver and secreted into bile, the iron is released and bound to transferrin (either returning to the start of cycle or stored in ferritin)
Hematocrit
volume percentage of RBC in the blood
Microcytic anemia
if hemoglobin is limited, cells will divide more times than usual causing them to be smaller (normally cell division stops when Hgb concentration reaches 20%)
Causes of microcytic anemia
deficiencies of iron, zinc (cofactor for heme synthesis) PLP (cofactor for ALA synthase) Copper (need by ceruloplasmin), also lead toxicity
Dietary fiber effects (4)
1) lowered serum cholesterol levels, 2) delayed gastric emptying, 3) interferes with nutrient absorption, 4) improved glucose tolerance
Trypsin activates:
colipase and phospholipase A2
Proteins involved in re-esterification in enterocyte
MGAT, DGAT, Acyl-CoA synthetase (ACS), Acyl-CoA cholesterol acyltranferase (ACAT)
essential fatty acids
Linoleic acid (omega-6) and linolenic acid (omega-3)
glycerol bound to FA chains with a:
ester bond
bile salts are reabsorbed in the:
ileum and are transported to liver via the hepatic portal vein
prechylomicron formation
occurs in the ER, MTP transfers lipids to apoB48, TAG, CE, phospholipids and apoB48 make up the prechylomicron
carbonic anhydrase
generates H+ for HCl in the stomach
Movement of H+ and Cl- into stomach
H+/K+ ATPase (primary active transport) and Cl- channel (facilitated)
Bile salts - lifecycle
Produced in the liver, stored in gall bladder, delivered to duodenum, used to emulsify lipid droplets and form micelles
CMC
critical micelle concentration - micelles can form when bile acids are present above this level
Molecules will increase in the plasma during starvation
ketone bodies, fatty acids, glucagon
Pantothenic acid is part of 2 molecules:
Coenzyme A and Acyl Carrier Protein
Mg2+ is important for ATP use because:
It neutralizes negative charges associated with phosphate molecules
GKRP
shuttles glucokinase in and out of the nucleus in hepatocytes
Glycogenin
initiates building of glycogen molecule
UTP
used for energy during glycogen synthesis
Lipoproteins secreted by the liver
VLDL, HDL
Apoproteins on chylomicrons in circulation
ApoA1, Apo-B48, ApoCII, ApoE
G-3-P
used for TG synthesis in adipocytes
SR-B1
uptake of cholesterol esters from HDL
chylomicron remnant receptor
LDLR and LRP
vitamin B12 structure
cobalamin, has heme type ring with a cobalt in the middle
vit B12 digestion - stomach
parietal cells provide intrinsic factor AND acidic environment to break things down/activate pepsin; salivary R-protein (transcobalamin1) binds B12 & protects it from acid
vit B12 digestion - small intestine
R-protein is hydrolyzed by pancreatic proteases, vit B12 is bound by intrinsic factor
vit B12 absorption
small amounts of B12 absorbed by passive diffusion, cubulin (IF receptor) binds B12-IF and internalized in ileum
Cubilin
IF receptor binds B12-IF complex, IF is degraded in the lysosome, cubilin is recycled back to apical membrane
LMBD1/ABCD4
transporter of B12 in cytoplasm
MRP1
transporter for vit B12 to exit enterocyte
transcobalamin II
binds B12 in plasma, can be taken in by cells through endocytosis
B12 - 2 important reactions
1) methylcobalamin: conversion of homocysteine to methionine 2) catabolism of proprionate, odd chain LCFA’s and some amino acids–> succinyl CoA
causes of vit B12 malabsorption
genetic: lack of IF (not absorbed), lack of cubulin (not absorbed), lack of transcobalamin (accumulates in enterocytes); acquired: gastric surgery or meds (impaired release from food), pancreatic insufficiency (B12 not released from R protein)
Megaloblastic anemia
cell division of RBCs does not occur (inhibition of methionine synthase interferes with DNA synthesis)
Folate sources
green leafy vegetables, citrus, whole grains, fortified cereals
Folates are absorbed in which form?
monoglutamate
GCPII
brush border enzyme cleaves polyglutamate folate derivatives
Proton coupled folate transporter
intestinal folate transporter (also found in liver)
DHFR
reduces folate
folypolyglutamyl synthetase
adds glutamate to folate
RFC
reduced folate carrier protein helps with folate export (so does MRP) and uptake into cells
Cofactors for “one carbon” metabolism
THF (tetrahydrofolate), vit B12 and SAM
Methylation
methionine (SAM) gives away methyl group, becomes homocysteine…. methyl-cobalamin uses methionine synthase to remake methionine….. to make methyl-cobalamin it comes from folate (5-THF) (serine donates a carbon to THF)
Methionine-methylation cycle
SAM is generated from methionine
SAM donates methyl group, forming S-adenosyl homocysteine
Adenosine is removed, forming homocysteine
Methionine is regenerated by transfer of a methyl group
Methionine synthase catalyzes the transfer from methyl-cobalamin
5-methyl-THF is used to regenerate methyl-cobalamin
Serine is used to regenerate 5-methyl-THF
B12 defiency effect on folate
folate becomes trapped as 5-methyl-THF (irreversible) and there is no B12 to donate methyl group to.
Thymidylate synthesis (required for DNA synthesis)
Thymidylate synthase - Transfer of a methyl group from 5,10-methylene THF to dUMP to form dTMP
Dihydrofolate reductease (DHFR) – Reduces DHF to THF
Serine hydroxylmethyl transferase (SHMT) – Transfer methyl group from serine to THF
- Regenerates 5,10-methylene THF
Folate deficiency
alterations in DNA methylation causing cancer, elevated homocysteine levels cause CVD
PDH (pyruvate dehydrogenase) requires what cofactors
CoA, FAD+ and NAD+
Riboflavin is important to which molecules
FMN, FAD
TPP
dephosphorylated to thiamin, necessary for PDH and KGDH
AMPK ______ insulin sensitivity
AMPK increases insulin sensitivity by encouraging glucose uptake that is independent of insulin
HMG CoA reductase
cholesterol synthesis
apoCII
activates LPL
apoA1
activates LCAT, allows HDL to bind to ABCA1
apoB48
required for chylomicron to be secreted from intestine
apoB100
ligand for LDL receptor, found in LDL/VLDL/IDL
apoE
ligand for LDL receptor
lipid re-esterification in enterocytes
Re-esterification process starts in the ER, Acyl coA synthetase (adds an acyl coA) → MGAT (add a FFA) → DGAT (add another FFA), Resulting TAG will be packaged into chylomicrons, in golgi added to apolipoproteins
Transport into mitochondria for B-oxidation
Palmitate is activated to palmitoyl-CoA via acyl-CoA synthetase; Palmitate-CoA is transported across the outer mitochondrial membrane by CPT I, which transfers palmitate from palmitoyl-CoA to carnitine, producing palmitoylcarnitine, CAT transports palmitoylcarnitine across inner mitochondrial membrane and delivers it to CPT II. CPT II transfers palmitate from carnitine to a CoA group to produce palmitoyl-CoA in the mitochondrial matrix
CPT I
palmitate CoA –> palmitoylcarnitine
CPT II
palmitoylcarnitine back to palmitoyl-CoA
ACS (acyl-CoA synthetase)
activates fatty acid by adding CoA
malonyl CoA
fatty acid synthesis
ATP per acetyl-CoA
12
ATP per cycle of B-oxidation
5
ACC
catalyzes flux generating step for FFA synthesis, citrate is an allosteric activator, glucagon reduces its activity, insulin increases its activity, requires biotin
Pantothenic acid required for:
initiation of synthesis of fatty acid from acetyl CoA
Phylloquinone
vitamin k1, main dietary source - leafy plants, found in supplements
Menaquinone
vitamin k2, produced by microbiota, some animal or fermented foods
Vitamin K has one job:
carboxylation in ER (cofactor for a carboxylase) – clotting factors need carboxylation: factors VII, IX, X and prothrombin
Vitamin K cycle
vit K is used by carboxylase, vit K is converted to an epoxide, vit K epoxide reductase regenerates vit K (target of warfarin)
Thrombin
cleaves fibrinogen into fibrin which forms insoluble fibrin clot with factor XIII, activates platelets
Osteocalcin
Contains three Glu residues that are converted to Gla residues
Abundant protein in bone secreted by osteoblasts
Required for bone mineralization
Vitamin K deficiency is associated with increased fracture and lower bone density
