Cell bio Lipids 2 & 3

Question 1

Digestion of dietary lipids (in monogastrics) starts in the what and what? and finishes in ?

Lipid digestion in the stomach is limited or not limited?
catalyzed by which enzymes?
and from are these enzymes secreted?

are both enzymes acid or base stable?
and they aka?

Acid lipases hydrolyze what? particularly which ones?

Acid lipases are very important for lipid digestion for which age group?

Answer 1

starts in the mouth and stomach, finishes in intestines

limited and catalyzed by
1. lingual lipase: produced by glands at back of tongue
2. gastric lipase: secreted by gastric mucosa cells in stomach

both are acid stable (pH 4-6) aka acid lipases

Acid lipases hydrolyze Triglycerides (TAG), particularly short (** IMP in milk fat) or medium chain length fatty acids

• for babies

Question 2

Lipid digestion is different from carbs and proteins
because they are ?

Detergent action is necessary to ? lipids so they can be?

Lipid assimilation can be divided in 4 phases: name them?

*Main organ for synthesis and secretion of lipases is?

Answer 2

hydrophobic

emulsify (dissolve) lipids so they can be digested by hydrolytic enzymes (lipases)

1. emulsification
2. hydrolysis
3. micelle formation
4. absorption

pancreas (pancreatic lipase)

Question 3

EMULSIFICATION

where does it begin? and then progress in?

what does it aim to do?

this is imp. for what?

what binds at the interface of droplet/aqueous solution

emulsification is accomplished by 2 complementary mechanisms: ?

bile salts are made of bile acids:
- made in which organ?
- stored in ?
- derivatives of cholestrol: phobic, phillic or amphiphatic?
- consist of which ring? w a side chain of amino acid
- emulsify what?

what is bile made of?

Answer 3

it begins in the stomach and progresses in the duodenum

aims to increase surface area of the **hydrophobic lipid droplets (smaller ones - emulsified have greater SA)
- crucial for lipase (hydrolase) function
- enzymes bind to. interface of droplet/aqueous solution

(smthn to mix these enzymes w the lipids and water so func. of emulsification reduces the size of lipid droplets which in turn increase the SA so hydrolytic enzymes to work)

1. mechanical mixing of peristalsis
2. use of detergent properties of conjugated bile salts

bile salts
made in liver
stored in gallbladder
amphiphatic derivatives of cholesterol
steroid ring
emulsify fat droplets

bile is made of bile salts, PL and free cholesterol

Question 4

DEGRDATION OF LIPIDS BY PANCREATIC ENZYMES

3 types of lipids that get degraded by pancreatic enzymes? and what are they hydrolyzed by and their end products?

Answer 4

1. triacylglycerol
   -too large for uptake by intestinal cells
   - hydrolyzed by pancreatic lipase and co-lipase
   end products: 1 monoglyceride and 2 FFA
2. cholesteryl ester (CE)
   - dietary cholesterol and CE are mostly from animal sources

enzyme: cholestrole esterase
activity of enzyme sped up by: bile salts
end products: cholesterol + FFA

3. PL (phospholipid)
   - pancreatic juice is rich in phospholipase
   (enzyme used here)
   activity of enzyme sped up by: bile salts
   end products: lysophospholipid and FFA

Question 5

fat droplets + bile salts = ?

? gets digested by lipases and digestion supported by bile salts and FFA which forms ?

Answer 5

emulsion droplets

micelles

Question 6

What are micelles?

The soluble mixed micelles transport the lipids from ? to ?
and into close contact with the absorptive surface of the ?

Answer 6

Micelles are aggregates of surfactant amphiphatic liquid molecules (bile salts and digested lipids) dispersed in a liquid (digestive juice), forming a colloidal suspension.

gut lumen to mucosal layer (epithelial cell layer) ..absorptive surface of enterocytes

Question 7

LIPIDS - Absorption by enterocytes

end products of lipid digestion?

which chain length are taken directly by enterocyte membrane (w/o the aid of mixed micelles)?

lipids combine with what to form mixed micelles?

primary site of lipid absorption?

bile salts are reabsorbed in the ? into the
hepatic portal system so that bile salt can be ?

Answer 7

FFA, free cholestrol and monoglycerides

short and medium chain length

lipids combine with bile salts and lipid soluble vitamins (A, D E, K) to form mixed micelles

Micelles move to the brush border membrane of
enterocytes (primary site of lipid absorption) and are
absorbed (except bile salts)

bile salts are reabsorbed in the ileum into the
hepatic portal system so that bile salt can be recycle by the liver

Question 8

LIPIDS - Re-esterification in enterocytes

Once absorbed into the enterocytes lipid mixture moves into the ? for ?

and then it goes into where for the formation of chylomicron?

Answer 8

sER for re-esterification of more complex lipids as follows:

monoglycerides (MAG) -> TAG triglycerides

Lysophospholipids -> phospholipids

cholestrol + fatty acids -> cholesteryl ester

then it goes into Golgi to form chylomicron i.e. a lipoprotein for lipid transport

Question 9

which chain fatty acids are not reesterified? and where (chain) are they released?

what are packed in the Golgi Apparatus into structures called CHYLOMICRON?

what is chylomicron?

Answer 9

short and medium chain and these chains are released into hepatic portal circulation where they bind to albumin and are carried to the liver

re-esterified lipids, cholestrol (from sER), proteins (from rER)

chylomicrons are lipoproteins, spherical struc. w a core of triglycerides and cholesterol ester and a surface of PLs

Question 10

LIPIDS - Secretion from ENTEROCYTES

PLASMA LIPOPROTEINS are?

Chylomicrons are released by exocytosis into the ?

Answer 10

highly hydrophobic TAG and cholesteryl esters must be packaged as lipid droplet particles surrounded by layer of PL, free cholestrol and protein for sustainability

lymphatic vessels (lacteals)
(-> and then to thoracic duct -> left subclavian vein -> blood)

Question 11

chylomicron, VLDL, LDL, HDL

which among them has highest cholestrol and is bad for u?

which among them has highest triacylglycerol?

which among them has lowest cholestrol and highest protein (good for u)?

Answer 11

1. highest cholestrol = LDL (bad for u)
2. highest triacylglycerol = chylomicron
3. lowest cholestrol and highest protein = HDL (high density lipoprotein)

Question 12

CONTROL OF LIPID DIGESTION:

Pancreatic secretion of *lipases (hydrolytic enzymes) is controlled by hormones: which ones? name 2

Answer 12

1. Cholecystokinin (CCK)
2. Secretin

Question 13

which cells produce the hormone cholecystokinin (CCK)?

produced in rxn to what? entering the small intestine?

CCK stimulates what?

2. Secretin is produced by what cells? and released in response to ?
   - stimulates secretion of what? in order to ?

Answer 13

1. Cholecystokinin (CCK) is a peptide hormone produced by I cells of the duodenum

• produced in rxn to lipids and proteins entering the small intestine
• CCK: stimulates section of bile from gallbladder and secretion of digestive enzymes from pancreas and it also decreases gastric mobility to give more time for emulsification

2. Secretin is a peptide hormone produced by the S cells of the duodenum and released in response to low pH of chyme (food content) from stomach
   - stimulates bicarbonate (HCO3) secretion form pancreas in order to neutralize pH -> optimum for pancreatic digestive enzymes

Question 14

small intesting divided into 55%, 5%, 40%

jejunum

duodejum

ileum

Answer 14

jejunum - 40%

duodejum - 5%

ileum - 55%

Question 15

USE of dietary lipids by the tissues

TAG from chylomicrons degraded to what and what? where? and by which enzyme?where enzyme located?

FFA will then enter?

chylomicron remnants where do they go?

Answer 15

TAG -> FFA + glycerol
- in the capillaries of peripheral tissue by enzyme lipoprotein lipase (LPL) located on endothelial cells of capillaries

FFA will then enter muscle cells or organ cells to produce energy or get stored in adipose tissue as TAG or remain in blood (bound to plasma proteins)

Glycerol -> enter liver to make glycerol - 3 - phosphate (glycolysis or gluconeogenesis)

chylomicron remnants: endocytosis by the liver so goes back to liver and hydrolyzed into remainder components and recycled.

Question 16

LIPIDS - fatty acid metabolism

Fatty acids are made from and oxidized to a common compound called ?

fatty acids are oxidized in the? and made in the ?

physiological conditions that promote FA synthesis largely inhibits?

preventing futile ?

Answer 16

acetyl coA

mitochondria and made in the cytosol

oxidation

cycling

Question 17

fatty acid synthesis occurs mainly in the cytosol of ?

can other tissues make FA? and where do they make it in?

animals make all the FAs they need except for the ? which must be supplied through ?

Shorter FA are made in
a. liver or
b. lactating mammary glands or c. adipose tissue?

Answer 17

liver cells (hepatocyte)
mammary glands
adipose tissue cells

Other tissues can make FA in small quantities, kidneys, brain, lungs

essential FA which must be supplied through diet

lactating mammary glands

Question 18

LIPIDS (de novo synthesis of fatty acids)

substrates of lipids are: ?

Primary product of lipids. are?

certain enzymes present in sER can cause desaturation of ?

what can be produced by desaturation + elongation?

Answer 18

substrates of lipids are excess carbohydrates and proteins from the diet
- acetyl coenzyme A (ACoA) from mitochondria (the process requires ATP and NAPDH)

Primary product of lipids are:

palmitate or palmitic acid (16 C) the primary end product of De novo FA synthesis
- can be further elongated in sER
- brain cells can produce v long FA needed for synthesis of brain phospholipids

a variety of polyunsaturated FA (PUFA) can be made by desaturation + elongation

Question 19

IN HEPATOCYTE

where does fatty acid synthesis occur?

if there high levels of citrate what does it indicate? and what does it get converted to then if high levels of it? and that in turn gets converted to. what ?

what is needed for the synthesis of fatty acid (palmitate)? (hint: 2 things one is enzyme)

citrate when high levels of energy come out of mitochondria where TCA cycle is occurring however where does elongation of fatty acid occur?

Answer 19

fatty acid synthesis occurs in cytosol

if there high levels of citrate it indicates there’s alr high energy molecule so it gets converted back to acetylcoA

fatty acid synthase and NADPH is required for fatty acid synthesis

elongation of fatty acid (palmitatE) occurs in ER

Question 20

LIPIDS - De Novo synthesis of FA

First list 3 main actions that take place during this

now explain the 3 main actions

The pentose phosphate pathway provides what?

palmitate is a fully unsaturated or saturated FA?

Answer 20

1. cytosolic acetyl CoA production
2. ACoA carboxylation to malonyl CoA
3. synthesis of palmitate

CYTOSOLIC acetyl CoA production:
- mitochondrial ACoA is produced mainly by oxidation of pyruvate by PDHC
- since CoA portion of ACoA cannot cross inner mitochondrial membrane it has to be incorporate into citrate
- citrate is produced by condenstaion of ACoA with oxaloacetate (OAA)
- citrate in the cytosol is then cleaved to OAA and ACoA by ATP-citrate lyase

***1. is stimulated when mitochondrial citrate is high which happens when -> ATP high -> means high energy signal

ACoA CARBOXYLATION (ACC) to malonyl CoA
- this is achieved by “acetyl coa carboxylase “ which is dependent on biotin (vit H or B7) and ATP are required in the carboxylation process
- This is the rate-limiting step and the regulated step in FA synthesis

*** ACC is allosterically activated by citrate and inactivated by palmitoyl CoA (pathway end product- negative feedback)

ACC synthesis is also stimulated by a high-calory and high-carb diet (nutrient availability) and hormone insulin: hormone of abundance)**

SYNTHESIS of palmitate 16:0

• All other reactions of fatty acid synthesis (in eukaryotes) are driven by the enzyme fatty acid synthase (FAS)
• The result is the production of palmitate (a fully saturated fatty acid, 16:0)
• This involves the addition of two carbons from malonyl CoA to the carboxyl end of a series of acyl acceptors (amino acid such as cysteine).

Pentose phosphate pathway provides reductant NADPH

Question 21

LIPIDS - Storage

how many FA in TAG and are they all the same type?

presence of unsaturated FA decreases the ? of lipid

Lipids caloric
value per unit mass is over ?
as great as carbs and protein

lipids stored as lipid droplets in ?

a small or big? part is stored in liver and released into blood as ?

what helps in the mobilization of fat (release from their TAG form aka ***lipolysis)?

Answer 21

3 F and C-1 is often saturated C2 unsaturated C3 either

presence of unsaturated FA decreases the tm of lipid

twice

Lipid stored as lipid droplets in adipocytes

a small part is stored in liver and released into blood as vldl

**hormone sensitive lipase (HSL) helps in mobilization of fat form adipose tissue (stimulated by glucagon and epinephrine)

Question 22

FATTY ACID β-OXIDATION

Major pathway for FA catabolism → Occurs where?

 Long chain fatty acids must form an active intermediate (fatty acyl
CoA) before ?

 The carnitine shuttle is required to transport what? into what?

Carnitine:
* Carnitine is a compound synthesized from amino acids ? in which organ?
and kidneys (abundant in mitochondrial membranes of muscle tissue)

• Carnitine can be taken up from the diet
  mostly from ?
• Carnitine deficiencies cause decreased ability of tissues to use ?
  this Can be caused by ?

Carnitine shuttle (CPT1) can be inhibited by ? so newly synthesized FA cannot be transferred into mitochondria to be degraded

fatty acid beta oxidation is a cyclic process, each cycle is catalyzed by enzymes with chain- length specificity
 Each cycle produces: ?

Answer 22

Major pathway for FA catabolism →Occurs in the mitochondria

 Long chain fatty acids must form an active intermediate (fatty acyl
CoA) before being oxidized inside the mitochondria

 The carnitine shuttle is required to transport fatty-acyl-CoA into the
mitochondria (rate limiting transport)

Carnitine:
* Carnitine is a compound synthesized from amino acids lysine and methionine in liver and kidneys (abundant in mitochondrial membranes of muscle tissue)

• Carnitine can be taken up from the diet
  mostly from animal products (red meat, poultry, dairy.)
• Carnitine deficiencies cause decreased ability of tissues to use LCFA as fuel
   Can be caused by cellular defects, genetic or medical conditions, or due to liver or kidney pathology

Carnitine shuttle (CPT1) can be inhibited by malonyl CoA, so newly synthesized FA cannot be transferred into mitochondria to be degraded

catalyzed by enzymes with chain- length specificity
 Each cycle produces: 1 acetyl-CoA + 1 NADH + 1 FADH2

Question 23

Each cycle produces:

Question 24

First cycle of beta-oxidation includes?

Oxidation of 1 palmitoyl CoA includes? how many ACoA, NADH and FADH2

Final products after full oxidation (beta oxidation, TCA cycle and OxPhos)?

**how much ATP needed for activation of palmitate to palmitoyl CoA (fatty acyl CoA)?

** so does oxidation of 1 molecule of glucose or 1 molecule of palmitoyl CoA (activated form of palmitate) yield greater energy/ATP?

Answer 24

First cycle of β-oxidation :
* A sequence of four reactions that involve the β-carbon (works on beta carbon) and cause the shortening of the FA by two carbons at the carboxyl end
[1] an oxidation that produces FADH2
[2] a hydration
[3] a second oxidation that produces NADH
[4] a CoA-dependent thiolytic cleavage that frees a molecule of acetyl CoA

Oxidation of 1 palmitoyl CoA: 8 ACoA, 7 NADH, 7 FADH2

Final products after full oxidation (beta oxidation, TCA cycle and OxPhos): ATP, CO2 and H2O

**how much ATP needed for activation of palmitate to palmitoyl CoA (fatty acyl CoA)? -> 2 ATP

oxidation of 1 molecule of palmitoyl coA yields greater energy as it yields 129 atp (more than glucose’s 36 ATP)

Question 25

1. Liver
   - liver glycogen becomes?
   - which are the 2 things present in here? e.g. triglyceride stores
2. Adiposse
   Adipose lipids become? and ? that enter blood (these “? ?” are stored in the triglyceride store)
3. Muscle
   Muscle glycogen can be used for ? muscles also use ? and break down their ? to amino acids that enter the blood
4. brain can only ? and ? for energy

ketone bodies are derived from ?

Answer 25

1. Liver
   - liver glycogen becomes glucose (through glycogenolysis)
   - liver glycogen stores and free fatty acids (from triglyceride store) are the 2 things present in here
2. Adipose
   Adipose lipids become FFA (used in liver and muscle) and glycerol that enter blood
3. Muscle
   Muscle glycogen can be used for energy.
   muscles also use fatty acids and break down their proteins to amino acids that enter the blood

(muscles include glycogen which either break down into pyruvate or lactate; pyruvate goes straight into making glucose while lactate uses gluconeogenesis to make glucose in the liver
- muscles can also ketone bodies (from beta oxidation of FFA in liver) for energy production)

4. brain can only glucose and ketone bodies for energy (ketone bodies are derived from beta oxidation of FFA in liver)

Question 26

LIPIDS - KETONES

The adult liver mitochondria can convert ACoA from fatty acid oxidation (beta oxidation) into ?

Acetoacetate and ß-hydroxybutyrate are free ?

 theses 2 are transported in the blood plasma to “A” (muscle, brain, kidney, mamary gland, small intestine, fetal liver)
 In “A” acetoacetate and beta-hydroxybutyrate can be converted back into acetyl CoA, which enters the ? for ATP production
 Can be used in the biosynthesis of ?
 Negative feedback on ? in adipocytes

if there is too much ketone bodies in blood then what happens?

what happens to acetone? (and where is it produced from?)

Answer 26

The adult liver mitochondria can convert ACoA from fatty acid oxidation (beta oxidation) into ketone bodies
→ acetoacetate, ß- hydroxybutyrate and acetone

Acetoacetate and ß-hydroxybutyrate are free soluble lipids

 theses 2 are transported in the blood plasma to peripheral tissues (muscle, brain, kidney, mamary gland, small intestine, fetal liver)
 In peripheral tissues, acetoacetate and beta-hydroxybutyrate can be converted back into acetyl CoA, which enters the TCA cycle for ATP production
 Can be used in the biosynthesis of glycerophospholipids, sphingolipids, and sterols
 Negative feedback on hormone sensitive lipase in adipocytes

Acetone is metabolically inert, can cause fruity smell on breath and urine of ketotic patients. (produced from acetoacetate)

Question 27

LIPIDS - KETONES

are important ** energy supply for ? because:

4 rzns

ketone bodies can save ?, imp. during fasting
- during fasting, fatty acids mobilized from ? move to the liver
- Fatty acid oxidation produces high amounts of ? (exceeding oxidative capacity of TCA/OxPhos in the liver) -> ACoA goes into ? instead of gluconeogenesis

what happens in ketolysis?

In normal conditions, the liver constantly produces low levels of ketone bodies
However, it increases during ? (or pathologic conditions such as diabetes mellitus) when ketone bodies are required as source of energy to ?

KETOLYSIS IN PERIPHERAL TISSUE

3-hydroxybutyrate is oxidized to ?

Acetoacetate + CoA molecule (thiophorase) → ?

Acetoacetyl CoA → ?

Ketone bodies (KB) synthesis occur in the ?
→ KB used in ?

 KB are hydrophilic so they are ?

 Mammalian RBC and liver cannot use KB as source of energy as
RBC lack ?
hepatocyte lack ?

Answer 27

LIPIDS - KETONES

are important ** energy supply for PERIPHERAL TISSUES because:

1. are *Water soluble, so can transported without albumin or lipoproteins
2. can cross blood-brain barrier and placental barrier
3. Are used proportionally to their concentration in the blood by extrahepatic tissue ( If concentrations are high enough cardiac and skeletal muscle, intestinal mucosa cells,
   renal cortex, brain, fetus can use ketone bodies)
4. are produced in the liver when there is an excess of ACoA present (too much for oxidative capacity of liver)

ketone bodies can save glucose, imp. during fasting
- during fasting, fatty acids mobilized from adipocytes move to the liver
- Fatty acid oxidation produces high amounts of NADH (exceeding oxidative capacity of TCA/OxPhos in the liver) -> ACoA goes into ketogensis instead of gluconeogenesis

KETOLYSIS IN PERIPHERAL TISSUE

3-hydroxybutyrate is oxidized to acetoacetate (NAD)

Acetoacetate + CoA molecule → acetoacetate CoA

Acetoacetyl CoA → 2 Acetyl CoA

Ketone bodies (KB) synthesis occur in the liver
→ KB used in peripheral tissues

 KB are hydrophilic so they are quickly transported via plasma

 Mammalian RBC and liver cannot use KB as source of energy as
RBC lack mitochondria
hepatocyte lack thiophorase