Block 2 Flashcards
is gluconeogenesis fast or slow to maintain blood glucose
slow
what is a rapidly mobilizable source of glucose
glycogen
what enzyme decides if the organ is involved in releasing glucose into the blood
glucose 6 phosphatase
glucose is stored in the form of __
glycogen
what is the main type of bond in glycogen
alpha 1,4-glycosidic (straight line)
*also have alpha 1,6- at branch points
glucose is stored as glycogen mostly in what 2 cells
liver and muscle
muscle uses glycogen for what
energy for itself
liver uses glycogen for what
blood glucose
why does muscle glycogen not contribute to blood glucose
absence of glucose 6-phosphatase
where does glycogenesis occur
cytosol
what is glycogenesis
synthesis of glycogen
glycogenesis requires energy supplied by __ and __
ATP
UTP
when does glycogenesis occur
if there is an excess of glucose in the blood
GLUTs are what type of molecule
protein
what is the committed step of glycogen synthesis
glucose 6-phosphate—>glucose 1-phosphate
the energy for glycosidic bond for glycogen is coming from __
UDP
the glycogen form used for glycogenesis is ___
UDP- glucose
what supplies the energy for bond formation of UDP-glucose in glycogenesis
PPi released from UTP
what is the enzyme of glycogenesis that makes glycogen structure, release UDP to connect glucose, and make alpha 1,4 bonds
glycogen synthase
what enzyme of glycogenesis, due to increased amount of linear glycogen structure, cuts alpha 1,4 bond to paste it a 1,6 position
branching enzyme
what is the primer enzyme/protein used in glycogenesis
glycogenin
what remains as the core of glycogen
glycogenin
what enzyme is used to shorten glycogen (glycogenolysis)
glycogen phosphorylase
what does glycogen phosphorylase do in glycogenolysis
break alpha 1,4 glycosidic bonds`
what coenzyme is required with glycogen phosphorylase
B6 (pyridoxal phosphate)
what is limit dextrin
any partly broken down starch
what is the function of phosphorylase in glycogenolysis
breaks alpha 1,4 glycosidic bonds, release glucose 1-P
what is limit dextrin found in glycogenolysis
where phosphorylase has acted but waiting for debranching enzyme to arrive
*can be seen on liver biopsy
what is the function of debranching enzyme in glycogenolysis
break 1, 4
make 1, 4
*creates straight line structure
break 1, 6 to release a free glucose
glucose 6-phosphatase is an enzyme for what 2 pathways
glycogenolysis and gluconeogenesis
what is the main function of glycogenolysis and glycogenesis
maintain blood glucose
what organ functions to maintain blood glucose
liver
a small amount of glycogen is degraded by ___ in the lysosome
alpha 1, 4- glucosidase (acid maltase)
what is Pompe disease
deficiency in alpha 1,4-glucosidase (acid maltase) in the lysosome causing an accumulation of glycogen in lysosome
in the liver in a fed states, glycogenesis or glycogenolysis predominates
glycogenesis
in the liver in a fasting state, glycogenesis or glycogenolysis predominates
glycogenolysis
in skeletal muscle, does glycogenolysis or glycogenesis occur during exercise
glycogenolysis
glucagon is related to __ (anabolic or catabolic) reactions, and responds to __ (high or low) glucose
catabolic
low
liver responds to what 3 things to start glycogenolysis
insulin/glucagon ratio
epinephrine
*hypoglycemia
muscle responds to what 3 things to start glycogenolysis
epinephrine
*high AMP (low ATP)
*calcium ions from contracting muscle
glucagon and epinephrine cause breakdown of glycogen using what type of receptor signals
G-protein coupled receptors
what is the 2nd messenger for hypoglycemia (glucagon release)
cAMP
glucagon activates __ enzymes
glycogenolysis
what are the 3 sources of glucose for use in the body (from 1st source to 3rd/final source)
food
glycogen stores
gluconeogenesis
glycogen is synthesized from what form of glucose
alpha-D-glucose
where does glycogenesis occur
cytosol
what is the committed step of glycogenesis and what enzyme is involved
glucose 6-phosphate–> glucose 1-phosphate by phosphoglucomutase
in glycogenesis, what acts as both an enzyme and a primer, and also remains at the core of a glycogen molecule
glycogenin
how does glycogen synthase differ from branching enzyme in regards to making/breaking glycosidic bonds
glycogen synthase makes alpha 1,4 bonds
branching enzymes break alpha 1,4 bonds then make alpha 1,6 bonds
where does glycogenolysis occur
cytosol
what are the 2 enzymes used in glycogenolysis
phosphorylase
debranching enzyme
the action of phosphorylase vs debranching enzyme in glycogenolysis differs in the type of glucose released. Phosphorylase releases ___ while debranching enzyme releases ___
glucose 1-phosphate
free glucose
insulin is related to __ (anabolic or catabolic) reactions, and responds to __ (high or low) glucose
anabolic
high
does glucagon activate or inactivate glycogen phosphorylase, leading to glycogen degradation
activates
how does insulin decrease the breakdown of glycogen
insulin activates phosphatase= dephosphorylation
dephosphorylation inactivates phosphorylase kinase leading to inactivation of glycogen breakdown
why does insulin decrease glycogen breakdown
insulin is released in a fed state
in a fed state we have enough glucose so we don’t need to use our storage
what 2 specific AA residues are commonly phosphorylated, leading to activation or inactivation
serine
threonine
what is the effect of insulin on phosphodiesterase
activates
so cAMP is deactivated, decreasing glycogenolysis, saving glycogen stores
what is the function of phosphodiesterase in glycogen metabolism
degrades cAMP (2nd messenger) into 5’-AMP to decrease breakdown of glycogen
if there is excess glycogen storage in the liver that can’t be broken down, the main symptom is ___
hypoglycemia
if there is excess glycogen storage in muscle, the main symptoms are __ and __
weakness
difficulty with exercise
what is a glycogen storage disease
defective glycogen synthase so no synthesis of glycogen
glycogen storage disease type 1 is also called
von gierke disease
what enzyme is involved in Von Gierke disease
defective glucose 6-phosphatase (in liver)
what are the 5 main presentations of Von Gierke disease
can’t release free glucose= severe fasting hypoglycemia
buildup of glycogen in liver= hepatomegaly
hyperuricemia
hyperlipidemia
lactic acidemia
what are the reasons behind the presentation of Von Gierke disease
glucose 6-phosphate isn’t converted to glucose, leading to a decrease in glucose release (fasting hypoglycemia)
glucose 6-phosphate overwhelms glycolysis, leading to an increase in lactate (lactic acidemia) and fatty acids (hyperlipidemia)
glucose 6-phosphate also acts in the pentose phosphate pathway and leads to an increase in uric acid (hyperuricemia)
when does Von Gierke disease typically manifest
6 months when an infant’s feeding schedule begins to be more spaced out
why do symptoms of Von Gierke disease likely arise during the fasting state
glucose is prevented from leaving liver cells and entering the bloodstream due to deficiency in glucose 6-phosphate
why is Von Gierke disease only associated with the liver and not muscle
muscle does not have glucose 6-phosphate, the deficient enzyme in Von Gierke disease
what is the treatment to Von Gierke disease
frequent oral glucose (meals) throughout the day
what enzyme is deficient in Pompe’s disease
lysosomal alpha 1,4 glucosidase (acid maltase)
Pompe’s disease is classified as a __ storage and __ storage disease
glycogen storage and lysosomal storage disease
what is the effect of Pompe’s disease
glycogen can’t be degraded in lysosomes= buildup of glycogen in lysosomes
what is the presentation of Pompe’s disease in juvenile onset
muscle hypotonia
cardiomegaly (leads to death by heart failure by age 2)
why is hypoglycemia not present in Pompe’s disease
the enzyme involved, lysosomal alpha 1,4-glucosidase) only accounts for 1-3% of glycogen breakdown
how does juvenile differ from adult onset of Pompe disease
juvenile= lysosomal alpha 1,4-glucosidase completely absent
adult= lysosomal alpha 1,4-glucosidase enzyme not completely absent
what is the enzyme affected in Cori disease
glycogen debranching enzyme (usually alpha 1,6-glucosidase component)
what are 2 other names for Cori disease
Forbes disease
Limit Dextrinosis
what gene mutation leads to Cori disease
AGL
what is the presentation of Cori disease
buildup of single glucose residue at branch-points or limit dextran present (partial glycogen degradation)
abnormal glycogen buildup= hepatomegaly
mild hypoglycemia
what is the defective enzyme in McArdle disease
muscle phosphorylase (myophosphorylase)
what is the presentation of McArdle disease
onset of exercise experiencing muscle aches, cramping
myoglobinuria (dark urine after exercise due to myoglobin in muscle breaking down)
what are the laboratory findings in McArdle disease
normal fasting blood glucose
normal glycogen structure in muscle biopsy
no plasma lactate after exercise (no glycogen metabolism)
what is the disease with an abnormal glycogen structure
Cori
why is there an absence of lactate in McArdle disease
we don’t have glucose because there is no metabolism of glycogen–>glucose
(first enzyme of glycogenolysis is defective)
what process clears the buildup of lactate during exercise
gluconeogenesis
what enzymes are released as a result of McArdle disease
creatine kinase
aldolase
what enzyme is defective in Hers disease
liver phosphorylase
what enzyme is defective in Anderson disease
branching enzyme
what is the main source of fructose
sucrose
where is sucrase present
brush border of intestine
what are the main sources of fructose in the diet
fruit
honey
corn syrup
table sugar (sucrose)
fructose is rapidly absorbed by ___
GLUT 5
is fructose transport into the cell insulin dependent
no
for fructose metabolism, it must first be phosphorylated by ___
fructokinase
what is the function of aldolase B in fructose metabolism
splits fructose 1-phosphate
what aldose is the only one that has affinity for fructose 1-phosphate in fructose cleavage
B
why is the rate of fructose metabolism faster than glucose
fructose 1-phosphate bypasses PFK-1, the rate limiting enzyme in glycolysis
what enzyme is deficient in essential fructosuria
fructokinase
what enzyme is deficient in hereditary fructose intolerance
aldose B
why is essential fructosuria benign
because of hexokinase, it can be partially used up and participate in glycolysis and the rest is excreted in the urine
*it doesn’t build up
where does fructose 1-phosphate get trapped
in cytosol
with aldose B deficiency, there is a buildup of fructose 1-phosphate, leading to what being trapped
phosphate
if the body’s phosphate is decreased, what does the patient feel
lethargic due to decreased ATP and drop in Pi (no glycogenolysis- glycogen needs to be phosphorylated)
hypoglycemia (trapping of phosphate)
hyperuricemia (trapping of phosphate)
what is the presentation for hereditary fructose intolerance
vomiting and hypoglycemia 20-30 minutes after fructose intake
when is hereditary fructose intolerance evident
when baby is weaned from milk and begins consuming food containing sucrose and fructose (ex: fruit)
how does hereditary fructose intolerance lead to hyperuricemia
our body has a limited store of Pi
Pi gets trapped with fructose
when all the Pi is trapped in our body stores, the rest of the fructose is excreted in the urine
what are the 2 main determinants of hereditary fructose intolerance
fructose in urine
aldose B deficiency
what is the treatment for hereditary fructose intolerance
remove fructose and sucrose from diet
what are 2 ways of trapping a monosaccharide (sugar)
add phosphate
add an alcohol group (polyol- a sugar alcohol)
what is the function of aldose reductase
reduce glucose to sorbitol
where is aldose reductase present
all tissues
what are the 2 enzymes involved in glucose–>fructose
aldose reductase
sorbitol dehydrogenase
what is the function of sorbitol synthesis
glucose–>sorbitol–>fructose
in sorbitol synthesis, what does aldose reductase do
converts D-glucose to D-sorbitol
in sorbitol synthesis, what does sorbitol dehydrogenase do
converts D-sorbitol to D-fructose
what is the effect of high glucose (hyperglycemia) in the body on sorbitol production
sorbitol increases
what is one of the main cell types that benefits from sorbitol synthesis (polyol pathway)
sperm cells which use fructose as their main energy source
what is the effect of long term hyperglycemia on cataract formation
high glucose= oversaturation of polyol pathway= glucose–>sorbitol
since sorbitol can’t cross the cell membrane, it’s trapped= increase in osmosis and oxidative stress= buildup of water= cataract formation
*similar to in kidneys and nerves
sorbitol= alcohol of __
glucose
in what tissues is insulin required for glucose entry (through GLUT4)
adipose
muscle
sorbitol dehydrogenase effect is the result of __ or __
oversaturation
physiological absence in nerves, kidney, and lenses
with cataract formation what enzyme is increased
aldose reductase
the buildup of __ leads to cataracts
sorbitol
what cataract formation, what enzyme in decreased
sorbitol dehydrogenase
what is the major source of galactose
lactose
what is the enzyme for digestion of lactose
beta-galactosidase (lactase)
*brush border intestinal enzyme
in galactose metabolism, what is the function of galactokinase
galactose–>galactose 1-phosphate
galactose 1-phosphate must be converted to UDP-galactose to enter glycolysis. the enzyme involved is ___
galactose 1-phosphate uridylyl transferase (GALT)
galactose is first converted to ___ before being broken down to glucose to enter into glycolysis
glycogen
what is the relation between glucose and galactose
C4 epimers
galactosemia is the result of what enzyme deficiency
galactokinase
what is the presentation of galactokinase deficiency
cataracts
galactosuria
how does galactokinase cause cataracts
galactose (aldose sugar) builds up, some is excreted, some isn’t
aldose reductase is activated
galactose–>galactitol= cataracts in 3-5 months
when is galactokinase deficient evident
days after birth with consumption of milk
what enzyme is deficient in classic galactosemia
galactose 1-phosphate uridylyltransferase
what is the treatment for galactosemia
removal of galactose/lactose from diet
addition of soy milk (contains sucrose which is metabolized to glucose and fructose)
nursing mother has galactosemia and can’t eat galactose. She can make galactose through what reaction via glucose
epimerization of glucose
if someone doesn’t eat galactose/fructose, how can they still make it (through what reaction)
epimerization of glucose
what are the 2 end products of the pentose phosphate pathway
NADPH
ribose
where does the pentose phosphate pathway occur
cytosol
what are the 2 reactions involved in the pentose phosphate pathway
oxidative
non-oxidative
oxidative, irreversible, pathways make __ and __
NADPH
pentoses
non-oxidative, reversible, pathways converts ___ to ___
glycolysis components
pentoses
what is the rate limiting step of pentose phosphate pathway
glucose 6-phosphate dehydrogenase
what is the first product following the committed step of pentose phosphate pathway
6-phosphogluconate
what is the first reaction of the pentose phosphate pathway that produced NADPH
glucose-6-phosphate dehydrogenase
what is the function of transketolase and transaldolase
shuffle carbons between glycolysis and pentose phosphate pathway
*links pentose phosphate pathway to glycolysis
transketolase in pentose phosphate contains a __ group as a cofactor
thiamine
what are the 3 symptoms of Wernicke syndrome
opthalmoplegia
confusion
ataxia
what causes Wernicke syndrome
thiamine deficiency especially in patients with alcoholism
*alcohol inhibits absorption of thiamine
what 3 pathways is thiamine (B1) used as a cofactor
pyruvate dehydrogenase
alpha-ketoglutarate dehydrogenase
transketolase
if a test is ordered to determine if a patient has thiamine deficiency, what enzyme is tested
transketolase
*it’s the only coenzyme used by the enzyme
thiamine deficiency results in decrease in what utilization
glucose
what is the treatment for Wernicke syndrome
IV thiamine followed by glucose infusion
what is a diagnostic for thiamine deficiency
RBC transketolase levels after thiamine infusion increases
transketolase is an enzyme of the oxidative or non-oxidative part of pentose phosphate pathway
non-oxidative
what is the main control regulator of the pentose phosphate pathway
NADP+ level
can the oxidative and non-oxidative pathway of pentose phosphate pathway function independently of each other
yes depending on the cellular requirement
from glycolysis to pentose phosphate pathway is oxidative or non-oxidative
oxidative
back to glycolysis is oxidative or non-oxidative
non-oxidative
what is the function of pentose phosphate in RBC
saves RBC from oxidative damage
what 3 AA make up glutathione
glutamate
cysteine
glycine
what helps protect RBC against oxidative stress
glutathione
is reduced or oxidized glutathione required for RBC protection against reactive oxidizing agents
reduced
what from the pentose phosphate pathway is used to maintain the reduced form of glutothione
NADPH
what are 2 effects of glucose 6-phosphate dehydrogenase deficiency
jaundice
hemolytic anemia
*due to oxidant stressors
what are Heinz bodies
oxidized hemoglobin conglomerates
when Heinz bodies are cleared by macrophages, leftover parts are called __
bite cells
glucose 6-phosphate dehydrogenase deficiency is what type of inheritance
X linked recessive
are glucose 6-phosphate dehydrogenase deficiencies usually 100% deficiency
no
what enzyme catalyzes the reduction of oxidized glutathione
glutathione reductase
why is glucose 6-phosphate dehydrogenase deficiencies most severe in RBC
it’s the only way for RBC to generate NADPH
hemolytic anemia can be the result of what 3 enzyme deficiencies
G6PD
glutathione reductase
glutathione peroxidase
G6PD deficiency is seen to provide protection against ___
malaria
what is the cytochrome p450 enzyme system
enzymes that works on foreign things in the body by adding an -OH group form hydroxylation and detoxification to make the foreign substance soluble for excretion
how is cytochrome 450 related to pentose phosphate pathway
it uses NADPH as it’s cofactor
what is the cause of chronic granulotamous disease
NADPH oxidase deficiency
what test is used to determine the presence of NADPH oxidase
nitroblue test
what are glycosides
sugars linked to other molecules through glycosidic bonds
what are glycosaminoglycans (GAGS)
linear glycans with >100 repeats of amino and acidic sugar dissacharides
what is the charge of amino sugars
+
what neutralizes the positive charge of amino sugars
acetylations
what is the charge of acidic sugars
negative
O linked sugars are linked to the OH of what 2 amino acids
serine
threonine
N linked sugars are linked to the NH2 of what amino acid
asparagine
what is glycosylation
enzymatic attachment of a sugar to another molecule
what is glycation
pathogenic, non-enzymatic attachment of excessive glucose to another molecule
in diabetes, persistently high glucose levels results in glycation of __, creating HbA1
hemoglobin
what is the enzyme used for O linked glycoproteins
glycosyl transferase
what is the trisaccharide core of O linked glycoproteins
GlcNAc/GalNAc-Gal-Neu5AC (NANA)
what is the pentasaccharide core of N linked glycoproteins
2 GlcNAc and 3 mannoses
in N linked glycoproteins, what is the terminal molecule in complex types
sialic acid
what is the function of dolichol phosphate in N linked glycoprotein synthesis
it acts as a scaffold for oligosaccharides before they are added to the amide nitrogen of asparagine
what is the main glycoprotein in mucous
mucin (an O glycoprotein)
what are the properties of mucins
negative charge (due to terminal sialic acid) makes them slippery and attracts water
what is the function of mucins
lubricate/hydrate
transport through GI, respiratory, and genitourinary tracts
protect epithelial surfaces
what are lectins
glycoproteins that bind to N linked sugars
what are the 2 components of influenza A that bind to host glycoproteins
HA binds sialic acid to allow entry into host cell
NA has sialidase activity to allow exit from host cell
what is the additional terminal sugar in type A blood antigen
N-Acetyl Galactosamine (GalNAc)
what is the additional terminal sugar in type B blood antigen
galactose
what is a cause of protein misfolding in regards to glycoproteins
abnormal glycosylation
how are glycoproteins transported from golgi to lysosome
mannose phosphorylation
what is a glycoprotein
oligosaccharide linked to a peptide
what is the charge of proteoglycans
negative
what are proteoglycans
core protein attached to GAG chains
what are GAGs (glycosaminoglycans) also known as
mucopolysaccharides
what is the structure of GAGs
repeating chain of alternating acidic sugar and amino sugar
what are the 2 common acidic sugars found in GAGs
iduronic acid
glucuronic acid
what are the 2 common amino sugars found in GAGs
glucosamine
galactosamine
what addition can be added to amino and acidic sugars of GAGs
they can be sulfated
sulfated sugars are found in all GAGs except ___
hyaluronic acid
GAGs provide __ and __
hydration
resilience (hydrophilic)
how are GAGs and proteoglycans involved in cartilage formation
proteoglycans and type II collagen form cartilage
how does penicillin inhibit peptidoglycan synthesis
interferes with transpeptidase which helps for bacterial cell walls
what type of inheritance is Hunter syndrome
X linked through mother
what type of inheritance is Hurler syndrome
autosomal recessive
what are the 3 types of complex lipids
phospholipids
glycolipids
lipoproteins
how many carbons make up a short chain fatty acid
how many carbons make up a medium chain fatty acid
how many carbons make up a long chain fatty acid
how many carbons make up a very long chain fatty acid
short= 3-5
medium= 6-12
long= 14-21
very long= 22 or more
what are 3 characteristics of saturated fatty acids
dense solids
high melting point
no double bonds
what are 3 characteristics of unsaturated fatty acids
low density liquids
low melting point
kinked with 1 or more double bonds
what are monounsaturated fatty acids
unsaturated fatty acid with only 1 double bond
what are polyunsaturated fatty acids
unsaturated fatty acid with more than one double bond
how do polyunsaturated fatty acids increase membrane fluidity
due to double bonds introducing kinks
is natural double bond configuration of fatty acids cis or trans
cis
the position of the __ determines the name of an unsaturated fatty acid
double bond
how does the delta naming system differ from the omega naming system of unsaturated fatty acids
delta identifies the double bond position from the carboxyl end
omega identifies the double bind position from the methyl end
what are the 2 essential fatty acids
linoleic acid
alpha- linolenic acid
what does it mean for a fatty acid to be essential
we must obtain it from out diet
the 2 essential fatty acids, linoleic acid and alpha-linolenic acid, are what type of fatty acids
polyunsaturated
what are the 3 health benefits of omega-3 essential fatty acids
anti-inflammatory
brain/neuron functioning
antithrombosis
what does omega-6 essential fatty acids do
precursor to make arachidonic acid and eicosanoids
pro-inflammatory and atherosclerosis
alpha-linolenic acid is an omega __ fatty acid
3
linoleic acid is an omega __ fatty acid
6
what is the role of eicosanoids (arachidonic acid) in inflammation and cell signaling
they act as hormones
why are trans fats harmful in human health
they decrease membrane fluidity and increase the risk for atherosclerosis and coronary heart disease
what are triglycerides
storage form of fatty acids
nonpolar
how do triacylglycerols (triglycerides) store energy
as fats and oils
what are the 3 types of membrane lipids
sterols
glycolipids
phospholipids
are membrane lipids hydrophilic, hydrophobic, or amphiphatic
amphipathic
nonpolar -phobic tail, -philic polar hear
what is cholesterol an important component of
cell membrane
bile salts are what type of molecule
cholesterol
what is the function of bile salts
assist in emulsification (micelle formation)
digestion
absorption of dietary lipids
bile salts are made of bile __
acids
what is the head group of the glycerophospholipid cephalin
ethanol amine
what is the head group of the glycerophospholipid phosphatidylserine
serine
what is the head group of the glycerophospholipid phosphatidalcholine (lecithin)
choline
cholesterol is a __
sterol
how do phytosterols in plants prevent the absorption of cholesterol from food
they compete with cholesterol for absorption site, inhibiting cholesterol absorption
which fat soluble vitamins contain a isoprene backbone
A
E
K
what 3 antibiotics are lipids (polyketides)
erythromycin
tetracyclin
doxycycline
what 2 molecules accumulate in Hunter syndrome
dermatan sulfate
heparan sulfate
what 2 molecules accumulate in Hurler syndrome
dermatan sulfate
heparin sulfate
what do lipoproteins transport
triglycerides
cholesterol
fat soluble vitamins (ADEK)
where are chylomicrons made
enterocytes
what is the function of chylomicrons
transport dietary lipids from the small intestine to muscle/adipose tissue
what are the 4 dietary lipids
triglycerides
cholesterol
vitamins
phospholipids
what is the essential apoprotein of chylomicrons
apo-B48
what apoproteins are present on chylomicrons
apo-B48
apoC-II
apo-E
where do chylomicrons get apoC-II and apo-E from
HDL
what is the function of apoC-II
activate lipoprotein lipase
what is the function of apo-E
mediate uptake of chylomicron and VLDL remnants in the liver
what is the function of lipoprotein lipase
convert triacylglycerides to 3 fatty acids+glycerol
what occurs with a defect in lipoprotein lipase or ApoC-II
increase plasma chylomicrons (hyperchylomicronemia)
what occurs with a defect in apo-E
increased remnants of chylomicrons and VLDL
(dysbetalipoproteinemia)
what is the effect of insulin on lipoprotein lipase
upregulates in fed state
where is VLDL made
hepatocytes
what is the function of VLDL
transport endogenous lipids (triacylglycerides, vitamins, and cholesterol) from the liver to tissues
what is the main integral protein for VLDL
apo-B100
what apoproteins are present on VLDL
apo-B100
apoC-II
apo-E
VLDL is can be converted to __ or __
IDL
LDL
what lipoprotein (VLDL, LDL, or HDL) delivers cholesterol to all cells
LDL
how does LDL deliver cholesterol to tissues
using apo-B-LDL receptor
how does LDL fom
derived from IDL
what is the function of LDL
transport and deliver cholesterol from liver to tissues
what is the only apoprotein on LDL
apo-B100
lipoprotein a is only find in patients with
hypercholesterolemia (modified form of LDL)
how can apo-A of lipoprotein A increase thrombosis
it’s a competitive inhibitor of plasminogen, inhibiting fibrinolysis
where is HDL made
in the liver
what is the function of HDL
bring cholesterol from tissues to liver
(“good”)
what apoprotein is needed for HDL
apoA-I
what are the apoproteins present on HDL
apoA-I
apoC-II
apoE
what does apoA-I do
activate LCAT which converts cholesterol–> cholesterol ester+lysolecithin
what is the function of apoA-I
trap and pack cholesterol esters
how do exogenous lipids differ from endogenous lipid
exogenous- dietary lipids digested by lipases and absorbed in the small intestine
endogenous- synthesized from excess glucose/AA in the liver
what enzymes account for the first breakdown of lipids
esterases
what type of fatty acids are readily absorbed into portal circulation without being emulsified
short and medium chain
what are the 2 substances make up micelles
digested lipids and bile salts
what are 5 substances that can be found in micelles
long chain fatty acids
monacylglycerols
cholesterol esters
phospholipids
vitamins ADEK
what is the structure of a micelle
outer layer- hydrophilic head, hydrophilic tail of phospholipid
inner core- hydrophobic lipids
what is the function of a micelle
transport of fatty acids
where are fatty acids esterified
SER
how are fatty acids activated
what enzyme is involved
fatty acyl-CoA synthase adds CoA (vitB5) to fatty acids
what makes up a chylomicron
dietary lipid+apolipoprotein
where does chylomicron formation occur
golgi
how is microsomal triacylglycerol transfer protein (MTTP) involved in chylomicron formation
loads apo-B48 and lipids on chylomicron
where are chylomicrons released into for transport
lymph
what is the structure of a chylomicron
core- triacylglycerols, cholesterol esters, vit ADEK)
outer layer- phospholipids, apo-B48
where is apo-B48 formed
rER
how does the drug orlistat (xenical) work
inhibits pancreatic and gastric lipase, preventing digestion and absorption of dietary fats
anti-obesity drug
what is the major side effect of orlistat (xenical)
steatorrhea (oily, loose stool)
how does the drug olestra work
it’s an artificial undigestible fat made of sucrose polymer so it isn’t degraded by gastric or pancreatic lipases
what are the side effects of olestra
diarrhea
abdominal cramps
steatorrhea
what are 2 foods with medium chain fatty acids
coconut oil
milk
what foods is omega 6 found in
sunflower, corn, and soybean oils
what foods is omega 3 found in
fish
flaxseen
walnuts
canola oil
soybean oil
what are the effects of cholecystokinin release
contraction/bile release from gallbladder
digestive enzyme release from pancreas
decreased gut motility to increase chyme contact with enzymes
when is secretin released from duodenal cells
in response to low pH of chyme entering the small intestine
how does secretin act
on pancreas to release bicarbonate ions leading to neutralization of the low pH chyme
MTTP is required in synthesis of __ and __
chylomicrons
VLDL
what are the 2 major carriers of triacylglycerols
chylomicrons
VLDL
list the plasma lipoproteins from highest density to lowest density
HDL
LDL
IDL
VLDL
chylomicron
list the plasma lipoproteins from largest to smallest
chylomicron
VLDL
IDL
LDL
HDL
list the plasma lipoproteins from highest triglyceride content to lowest triglyceride content
chylomicron
VLDL
LDL
HDL
list the plasma lipoproteins from highest cholesterol content to lowest cholesterol content
LDL
HDL
VLDL
chylomicron
list the plasma lipoproteins from highest protein content to lowest protein content
HDL
LDL
VLDL
chylomicron
what is the rate limiting enzyme of bile acid synthesis
7-alpha hydroxylase (+vit c)
a deficiency in 7-alpha hydroxylase can lead to ___
gallstones
what is the rate limiting step of cholesterol synthesis
HMG CoA–>mevalonate
by HMG CoA reductase
the transcriptional rate of HMG CoA reductase is controlled by __
SCAP not bound to cholesterol
=SREBP to nucleus for transcription of HMG CoA reductase gene
where does cholesterol synthesis occur
smooth ER
what causes atherosclerosis
increase in ox-LDL (oxidized LDL leads to foam cell deposition in vessels
what is the rate limiting step of beta oxidation
acyl CoA dehydrogenase
what is the rate limiting step of fatty acid oxidation
carnitine acyltransferase I
what is the rate limiting enzyme of fatty acid synthesis
acetyl CoA carboxylase
where does fatty acid synthesis occur
cytoplasm
where does beta oxidation occur
mitochondria
in the citrate shuttle of fatty acid synthesis, what enzyme produces NADPH
malic enzyme
what is absence or defective in abetalipoprotein
MTTP
what is abetalipoprotein
absence beta lipoproteins (chylomicrons, VLDL, LDL)
very low cholesterol and TAG
usually due to absence of MTTTP
what is deficient in hyperchylomicronemia (type I familial hyperbetalipoproteinemia)
ApoCII or LDL
what is deficient in hypercholesterolemia (type II familial hyperbetalipoproteinemia)
ApoB100 or LDL receptor
what is the lab diagnosis for abetalipoproteinemia
very low plasma TAG and cholesterol
what is the optimum level for triglycerides
<150 mg/dL
what is the optimum level for total cholesterol
<200 mg/dL
what is the optimum level for LDL cholesterol
<100 mg/dL
what is the optimum level for HDL cholesterol
60 or greater
(low= <40)
what is the optimum ratio of LDL:HDL
< 3.0
(LDL should be 3x less than HDL)
deficiency in lipids or fat soluble vitamins in children leads to what symptoms
growth failure and mental retardation
neurological problems
what are the main signs of hypercholesteremia
yellowed plaques of skin (xanthoma)
near tendons, palms, and eyes
chest pain/easy fatigue
what are the main signs of hypertriglyceridemia
eruptive xanthoma (reddish papules)
pancreatitis
obesity
upper abdominal pain
in hyperlipidemia, what lipoprotein level is decreased
HDL
in familial hyperlipidemia, there is an increase in what in each:
type I
type II
type III
type IV
I= chylomicron and TAG
II= LDL
III= chylomicron and VLDL remnants
IV= VLDL
what is the optimum triglyceride (VLDL) level
<150
what is the optimum total cholesterol level
<200
what is the optimum LDL level
<100
what is the optimum HDL level
> /= 60
what is the optimum LDL:HDL ration
<3
what is the function of dipalmitoylphosphatidyl choline (DPPC)
part of surfactant that line inner surface of alveoli to lower surface tension, preventing collapse
how does surfactant work
decrease hydrogen binding, preventing alveolar collapse
prior to birth, what hormone is used to induce production of surfactant (DPPC)
cortisol
in pre-mature born babies, DPPC levels are low. what has to be administered as a result
DPPC by intratracheal injection
what is the function of cardiolipin
found in inner mitochondrial membrane where it maintains the structure and function of ETC
if the L:S ration is <2 in premature babies, what is the result
immature pneumocytes, lung collapse due to less DPPC in alveoli
where are ether glycerophospholipids formed
peroxisomes
what are the bonds found in ether glycerophospholipids
C1 of glycerol forms an ether with alkyl or alkenyl hydrocarbon
what type of molecule is platelet activating factor
ether glycerophospholipid derived from phosphatidylcholine (lecithin)
what is multiple sclerosis
autoimmune demyelination of motor neurons
where are glycolipids mostly found in the plasma membrane
outer leaflet of bilayer facing extracellular syrface
what are 3 types of sphingoglycolipids
cerebroside
globoside
ganglioside
glucocerebrosides occur in the plasma membrane of ___ cells
glucocerebrosides occur in the plasma membrane of __ cells
non-neuronal
neuronal
do globosides contain NANA (sialic acid)
no
what are gangliosides
glycosphingolipid with 1 or more sialic acid
saccharolipids are made up of ____
fatty acids esteridied to a sugar backbone without glycerol/sphingo backbone
what are 2 examples of bacterial liposaccharides (glycolipids)
cholera and tetanus toxins
where are phospholipids degraded
lysosomes
glycerophospholipids are degraded by what enzyme
phospholipases
where are sphingolipids degraded
lysosome
