Cell Metabolism II Flashcards
what are the 5 main classes of lipids?
free fatty acids triacylglycerols phospholipids glycolipids steroids
What are fatty acids?
hydrocarbon chains with a terminal carboxylic acid group
What does saturated mean?
Absence of double bonds
every carbon atom is attached to 4 other atoms
How are fatty acids stored in the cytoplasm of cells?
in the form of triacylglycerols
What are triacylglycerols?
Molecules composed of 3 fatty acids attached to a glycerol molecule
attachments: ester linkages
What do the ester linkages do to the carboxylic acid groups?
Neutralise them to help keep the pH of cells in a normal range
What are the characteristics of fatty acids?
reduced and anhydrous
ideal storage molecules
What does fatty acid metabolism lead to?
Acetyl CoA production
how are fats broken down?
Fats –> fatty acids –> acetyl CoA (produced in mitochondria)
What are the 3 sources of fats?
diet
De novo biosynthesis (liver) (production of fats)
storage deposits in adipose
What are bile salts generated from and where?
cholesterol
in the liver
stored in the gal bladder
What are bile salts?
They have a hydrophobic part and a hydrophilic part
What is the role of bile salts?
Solubilize fatty acids
What happens with bile salts during digestion?
they pass from the bile duct into the intestine
they emulsify fats in the intestine, aiding their digestion and absorption of fats and also that of fat-soluble vitamins
what are fat-soluble vitamins?
A,D,E and K
What does a lack of bile salts result in?
the majority of fats passes through the gut undigested and unabsorbed resulting in steatorrhea (fatty stool)
What is orlistat?
A protein inhibitor of gastric and pancreatic lipases
a chemically synthesised derivative of lipstatin, a product of Streptomyces toxytricini
What does orlistat do?
reduces fat absorption by 30% which is almost completely excreted by the faecal route
What is it effective in treating?
obesity ( for up to 2 years)
main side effects: abdominal pain, urgency to defecate, increased flatus and steatorrhea
How are fats transported around the body?
transported in the plasma by lipoproteins which are categorized according to their density
chylomicrons (CM) lipoproteins
source: intestines
role: dietary fat transport
very low density lipoproteins (VLDL)
source: liver
role: endogenous fat transport
intermediate density lipoproteins (IDL)
source: very low density lipoproteins (VLDL)
role: LDL precursor
low density lipoproteins (LDL)
source: intermediate density lipoproteins (IDL)
role: cholesterol transport
high density lipoproteins (HDL)
source: liver
role: reverse cholesterol transport
What is the chylomicron?
a molecule that transports dietary fats
How are dietary products absorbed?
by enterocytes
what are enterocytes?
cells that line the brush border of the small intestines
what happens to the dietary fats when they’re ingested?
triglycerides are resynthesized under the control of several enzymes prior to incorporation into chylomicrons (CM)
Where are chylomicrons transported?
via the lymphatics and on into the bloodstream
When do chylomicrons acquire apoproteins from HDL?
following the release of the bloodstream
what is the structure of chylomicron?
a layer of phospholipid on the outside with embedded apoproteins and triglycerides inside the spherical shape
What do lipases breakdown?
lipoproteins
How do chylomicrons enter the bloodstream?
CMs travel from the lacteals of the intestine to the thoracic duct and to the left subclavian vein
Where is lipoprotein lipase located?
on the capillary endothelial cells lining a variety of tissues including adipose, heart and skeletal muscle
What do fatty acids undergo?
β-oxidation
Where does glycerol return?
to the liver for use in gluconeogenesis
lifecycle of chylomicrons
intestinal villus –> nascent chylomicron –(HDL)–>transfer of apoproteins–> the triglycerides are broken down to glycerol + free fatty acids
chylomicron remnants can pick up more HDL and these are recognised by the liver
what is embedded in the chylomicrons membrane and found inside?
cholesterol
what are cholesterol esters?
synthesized in the plasma from cholesterol and the acyl chain of phosphatidylcholine (lecithin) via a reaction catalyzed by lecithin: cholesterol acyltransferase (LCAT)
cholesterol + phosphatidylcholine –(LCAT)–> cholesterol ester + lysophosphatidylcholine
life cycle of VLDL, IDL, HDL, LDL
liver–> VLDL –(glycerol + ffa)–> lipid-depleted remnant –(transfer of apoproteins HDL)–> IDL –(transfer of CE from HDL)–> LDL which is either taken up by the liver or macrophages
What is HDL?
“good cholesterol”
take cholesterol from peripheral tissues back to the liver for use or disposal
lower total serum cholesterol
What is LDL?
“bad cholesterol”
prolonged elevation of LDL levels lead to atherosclerosis (hardening of the arteries)
transport cholesterol synthesised in the liver to peripheral tissues with more than 40% of their weight is made up of cholesterol esters
What is the caloric yield from fatty acids?
twice as much as carbohydrates
STEP 1: β-oxidation of fatty acids reaction
fatty acid + ATP + HS – CoA –(ACYL CoA SYNTHETASE)–> acyl CoA + AMP + PPi
ATP –> AMP (adenosine monophosphate)
Where does the generation of the Acyl CoA species occur?
on the outer mitochondrial membrane
What is acyl CoA coupled with to be transported into the matrix?
carnitine to form acyl carnitine
How are carnitine and acyl carnitine moved to and from the matrix?
translocase
STEP 2: the carnitine shuttle
carnitine+ Acyl CoA–> Acyl carnitine + CoA
enzyme: CARNITINE ACYLTRANSFERASE I
acyl carnitine moved into the matrix
acyl carnitine + CoA –>carnitine + Acyl CoA
enzyme: CARNITINE ACYLTRANSFERASE II
carnitine is moved back out
What is primary carnitine deficiency?
autosomal recessive disorder
symptoms: cardiomyopathies, muscle weakness, hypoglycemia)
mutation in gene–> reduced ability of cells to take up carnitine needed for β-oxidation of fatty acids
What happens in the β-oxidation cycle?
The acyl CoA undergoes a sequence of oxidation, hydration, oxidation and thiolysis reactions (collectively called β-oxidation)
this results in the production of one molecule of acetyl CoA and an acyl CoA species which is 2 carbons shorter than the original
overall reaction of β-oxidation of palmatic acid?
(16 carbon) palmitoyl CoA + 7 NAD+ + 7 H2O + 7 CoA –> 8 acetyl CoA + 7 FADH2 + 7 NADH
7 cycles
what does acetyl CoA enter?
the TCA cycle only if β-oxidation and carbohydrate metabolism are balanced, since oxaloacetate is needed for entry
What happens when fat breakdown predominates?
fasting
acetyl CoA forms acetoacetate, D-3-hydroxybutyrate and acetone known as ketone bodies
enzymes: 1: 3-ketothiolase
2: hydroxymethylglutaryl CoA synthase
3: hydroxymethylglutaryl CoA cleavage enzyme
4: D-3-hydroxybutyrate dehydrogenase
How many ATP molecules are made from the oxidation of palmitoyl?
35 from β-oxidation and 96 from 8 TCA or Krebs cycle= 131
2 ATP are used in acyl CoA so =129 ATP
What enzymes are involved in fatty acid biosynthesis?
acetyl-CoA and malonyl-CoA
What reactions form fatty acids?
decarboxylative condensation reactions involving the molecules acetyl-CoA and malonyl-CoA
how else is fatty acid biosynthesis called?
Lipogenesis
What reactions do fatty acids undergo?
reduction and dehydration by the sequential action of a ketoreductase (KR), dehydratase (DH), and enol reductase (ER) activity
What is the growing fatty acid group linked to?
an acyl carrier protein (ACP)
what is the overall reaction of fatty acid synthesis?
ACTIVATED ACETYL GROUP + ACTIVATED MALONYL GROUP
condensation–> reduction–>dehydration–> reduction–>
ACTIVATED ACYL GROUP ( lengthened by 2 C atoms)
What is the overall reaction of fatty acid degradation? (β-oxidation )
ACTIVATED ACYL GROUP
oxidation–> hydration–> oxidation–> cleavage–>
ACTIVATED ACYL GROUP (shortened by 2 C atoms) + ACTIVATED ACETYL GROUP
Distinctions between synthesis and degradation?
carriers: ACP vs CoA
reducing power: NADPH v FAD/NAD+
locations; cytoplasm v mitochondrial matrix
Overall reaction of lipogenesis?
Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+ ---> Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+
What does the desaturation of fatty acids require?
the action of fatty acyl-CoA desaturases
What is ∆-9 desaturase?
The enzyme that creates oleic acid and palmitoleic acid from stearate and palmitate
it generates a double bond nine carbons from the terminal carboxyl group
Where does FA biosynthesis happen in adults?
liver, adipose tissue and lactating breast
What are Disorders of β-oxidation?
Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD)
c6-c12
Autosomal recessive. Predominantly occurring in Caucasians
If undiagnosed, can be fatal
not good at breaking down fatty acids for e
get most cals from carbohydrates
no long fasts (10-12 hours)
Fatty acids within deposits are non-esterified and transported by?
albium
the majority of FA we consume are even chain length
But odd chain length result in?
3 c propionyl CoA on final oxidation
undergoes a series of reactions that yields succinyl-CoA which can enter the TCA cycle
