lipid metabolisam Flashcards
when does ketone body metabolism take place
starving
where does ketone metabolism takes place
liver
what is the reaction takes place while producing ketone bodies
liver converts excess CoA from beta oxidation of fatty acids into ketone bodies
what are the example of ketone bodies
- Acetone
- Acetoacetate
- 3-hydroxybutyrate
which tissues will use ketone bodies as a source of energy
extrahepatic tissues like brain muscles etc
why does liver cannot use ketone bodies as a source of energy
liver does not contain succinyl CoA acetoacetyl CoA transferase (Thiosphosase)
name which part in our body metabolize acetoacetate and beta hydroxybutyrate to acetyl CoA
cardiac and skeletal muscle and renal cortex
what is ketogenisis
biochemical process by which organisms produces ketone bodies
how ketone bodies are produced
by the breakdown of fatty acids
at what circumstances ketogenisis occur
fasting and hypoglycemia
exessive production of ketone bodies leads to a dangerous state known as
ketoacidosis
when will brain begin to metabolize ketone body
after a week of fasting ketones reach a concentration in blood high
where will ketogenesis occurs
in mitochondria of hepatocytes
when will ketogenesis occur
when excess acetyl-CoA accumulates in the fasting state
name the enzyme that produce HMG- CoA
3-Hydroxy 3-Methyle Glutaryl-CoA (HMG-CoA) synthase
HMG-CoA lyase breaks ____________ into ____________
HMG-CoA into acetoacetate
name the ketone body that produced as a minor side product formed non enzymatically
Acetone
if acetone is used as a fuel it leads to
strong odor (sweet or fruity) to the breath
what are the condition favoring ketogenesis
fasting
carbohydrate restrictive diets
starvation
prolonged intense exercise
untreated type 1 diabetes mellitus
ketone bodies are converted into __________ by extrahepatic tissues which then enters the ____________and oxidized in the mitochondria
acetyl CoA , citric acid cycle
in brain ketone bodies are also used to make acetyl CoA into
long chain fatty acids
why acetyl CoA is converted to LCFA in brain
LCFA cannot be obtained from blood ( cannot pass through blood brain barrier)
how ketone bodies are generated in patients with type 1 diabetes mellitus
glucose- high , no insulin , hormone sensitive triglyceride lipase (HSL) is active, beta oxidation is not inhibited
ketoacidosis in type 1 diabetes mellitus patients
ketoacidosis in type 2 diabetes mellitus patients
develop after an infection or trauma
how ketoacidosis is developed in alcoholics
chronic hypoglycemia present in chronic alcoholism favors fat release from adipose tissue
why utilization of ketone is slower in alcoholics even though liver increase the production of ketone bodies
alcohol is converted to acetate in the liver diffuses into blood and oxidize by muscle as an alternative source of acetyl CoA
ketoacidosis is characterized by
polyuria, dehydration, & thirst
CNS depression and coma
potential depletion of k+
decreased plasma bicarbonate
breath with a sweet or fruity odor due to acetone
what is the difference between normal ketosis and pathological condition
acetoacetate and beta hydroxybutyrate are formed aprox. equal quantites in normal and their ratio sift in pathology , beta hydroxybutyrate predominates
what is ketogenic diet
high fat, adequate-protein, low carbohydrate diet
ketogenic diet is used primarily to treat
difficult-to-control epilepsy (forces the body to burn fats rather that carbohydrate)
when will liver depends on fatty acid oxidation and synthesize ketone bodies
if there is very little carbohydrate
ketosis leads to
reduction of epileptic seizures
what are sphingolipids
imp constituent of cell membrane
similar structure to the glycerophospholipids have a hydrophilic region and 2 fatty acid derived hydrophobic tails
various classes of sphingolipids differ primarily in
nature of the hydrophilic region
give example of sphingolipids and their hydrophilic group
sphingomyelin: phosphorylcholine
cerebrosides: galactose or glucose
gangliosides : branched oligosaccharides
what is released when membrane is degraded and digested in endosomes after fusion with lysosome
spingolipids
what is the action of enzymes in lysosome
removes specific groups from individual sphingolipids
which is the x-linked recessive sphingolipidosis
fabry disease
what are the autosomal recessive sphingolipidoses
tay- sachs, Gaucher, niemann-pick
fabry is caused by mutation in the gene that encodes
lysomal enzyme alpha- galactose
(Ceramide trihexoside accumulates in the lysosomes)
symptoms of fabry diseases
*burning sensation in the hand which get worse with exercise and hot weather
*small, raised reddish- purple blemishes on skin(angiokeratomas)
*eye manifestation
*impaired arterial circulation and increased risk of heart attack or stroke
*enlargement of heart and kidney
what is the treatment for fabry disease
enzyme replacement therapy
what are the components of bile
watery mixture of organic and inorganic compounds
what are the composition of bile
water-97%
bile salt-0.7%
bilirubin-0.2%
fat- (cholesterol, fatty acids & lecithin)
inorganic salt-200 meq/l
what are the important organic components of bile
phosphatidylcholine(pc), lecithin, and conjugated bile
how is bile is secreated
directly from liver into duodenum through the common bile duct or stored in gall bladder
how many carbons are there in bile acid and what are the other groups
24 carbon with 2 or 3 hydroxyl group and side chain that terminate in a carboxyl group
what are the orientation of bile salt and acid
hydroxyl grp- alpha
methyl grp- beta
describe the polarity of bile molecule
have both a polar and a nonpolar surface
what is the function of bile
act as a emulsifying agent in the intestine
helping prepare dietary fat & other complex lipids for degradation of pancreatic enzymes
what are the most abundant bile acids in human bile
cholic acid and chenodeoxycholic acid
bile acids are synthesized in the liver by a _________ and _________ pathway
multistep, multiorganelle
on what structure hydroxyl grps are inserted at a specific position
steroid structure
how is bile salt acid synthesis from cholesterol
double bond of cholesterol B ring is reduced and hydrocarbon chain is shortened by 3 carbons, introducing a carbonyl grp at the end of the chain
name primary bile acids
cholic acid (triol), chenodeoxycholic acid ( diol )
most common resulting compound
the rate limited step in bile acid synthesis is the introduction of a
hydroxyl group at C7 of steroid nucleus by 7-alpha-hydroxylase
name the enzyme that is an associated cytochrome p450 (CYP) monooxygenase with found only in liver
7-alpha-hydroxylase
expression of cholesterol-7-alpha hydroxylase is upregulated and downregulated by
cholesterol
bile acid (cholic acid )
why chenodeoxycholic and not cholic acid, can be used to treat gallstones
because decreasing bile acid synthesis via inhibition of cholesterol-7-alpha hydroxylase would supersaturate the stones even more
Which receptor is stimulated with elevated levels of cholesterol in the liver
nuclear receptor liver X factor (LXR)
LXR increases the transcription of
cholesterol -7-alpha hydroxylase
name the nuclear receptor that activates on elevated level of bile acids
bile acid receptor ( BAR) or farnesoid X receptor (FXR)
BAR will downregulate the transcription of
cholesterol-7-alpha hydroxlase
the carboxyl group of bile acid is conjugated by amide bond to a molecule of either __________ or ________ before living liver
glycine or taurine (end product of cysteine metaboisam
the new molecule after conjugation are called
glycocholic, glycochenodeoxycholic acids and taurocholic and taurochenodeoxycholic acid
the ratio of glycine to taurine forms in the bile is
3/1
which type of ionized bile salts are more effective detergent, why
conjugated one, because of their enhanced amphipathic nature
which form of bile salts are found in bile
only the conjugated form
individuals with genetic deficiencies in the conversion of cholesterol to bile are treated with
exogenously supplied chenodeoxycholic acid
bile salt provides significant mechanism for cholesterol excretion, both as a
metabolic product of cholesterol & solubilizer of cholesterol in bile
bile salt secreted into the intestine are efficiently __________&___________
reabsorbed and reused
bile salt efficiently taken up from the blood by the hepatocytes via
an isoform of the cotransporter
what binds with the bile salts and transport them through the blood
albumin
how is secondary bile salts are forms
some bile salt from cycle is deconjugated the dehydroxylated
the secondary bile salts are uptaken in the
_________ and subsequent return to liver as a
ileum
mixture of primary and secondary forms
how much bile salt is secreted by liver daily and how much lost daily
30 g
0.5 g
0.5 g that lost is synthesized from ___________ in the liver to replavce the lost amt
choleaterol
name one bile acid sequestrants
cholestramine
how bile acid sequestrants promote their excreation
they bind bile salt in the gut and prevent their reabsorption
bile acid sequestrants are used in the treatment of
hypercholesterolemia
how hypercholesterolemia treatment works
removal of bile salt relieves the inhibition on bile acid synthesis in liver thereby diverting additional cholesterol into that pathway
dietary fiber also binds bile salt and increases their excretion
where and by what bile salts are exposed to bacterial modification b
in the colon by gut microbiome
what are the secondary bile acid
deoxycholic acids from cholic acid
lithocholic acid from chenodeoxycholic acid
how is secondary bile salts are produced
by dehydroxylate carbon 7
a small proportion of these secondary bile acids are absorbed by the
colonic epithelium
the movement of cholesterol from the liver into bile must be accomplished by the
simultaneous secretion of phospholipid and bile salts
if cholesterol may precipitate in the gallbladder, leading to
cholesterol gallstone disease or cholelithiasis
cholelithiasis is caused by a
decrease of bile acids in the bile
choleolithiasis also may result from
increased secretion of cholesterol into bile with the use of fibrates to reduce cholesterol in blood
example of fibrate
gemfibrozil
what is the treatment method for cholelithiasis
laparoscopic cholecystectomy
treatment for patients who cannot undergo surgery is
oral administration of chenogeoxycholic acid
fatty acid synthesis is also known as
de novo synthesis (new synthesis from amphibolic compounds )
lipogenesis
sites of fatty acid synthesis
liver, kidney, brain, lungs, mammary gland & adipose tissue
organelle of fatty acid synthesis
cytosol
which is the principal building block of fatty acid
acetyl CoA
name the method of synthesis of saturated fatty acids from acetyl CoA that is primarily derived from glucose, and occurs in
de novo synthesis
cytoplasm
elongation of fatty acids are and occurs in
acetyl fragments are added to the existing FAs
occurs in cytoplasm and mitochondria
double bonds introduced into the FAs are called and occurs in
desaturation of fatty acids
microsomes
what all steps of FA synthesis occur in mitochondria
catabolism by beta-oxidation
some chain lengthening
chain lengthening and introduction of double bonds occur in
endoplasmic reticulum
anabolism & formation of acyl-CoA occur in `
cytosol
the process in which C2 acetyl CoA converted to C16 palmitic acid is
De Novo synthesis
major FA synthesised in denov is
palmitic acid
which is the source of carbon atoms in FA synthesis
Acetyl CoA
NADPH id the source of _________ in FA synthesis
reducing equivalents
source of energy in FA synthesis
ATP
source of acetyl CoA is
aerobic glycolysis
FA oxidation
source of NADPH
HMP shunt pathway
malic enzyme (NADP malate dehydrogenase)
the extra
