Today’s topics:

1. Classification and characterization of lipid

2. Function
3. Digestion and absorption
4. Lipid metabolism in fed state:
- Fatty acids synthesis
- TAG synthesis
5. Lipid metabolism during fasting:
- Lipolysis
- Beta oxidation
- Ketogenesis
6. Eicosanoids
 CLASSIFICATION
Simple Lipids
Neutral fats – Triglycerides (TAG)
Waxes - Beeswax

Compound Lipids
Phospholipids - Lecithins, cephalins
Glycolipids - Cerebrosides, gangliosides
Lipoproteins - Chylomicrons, VLDLs, LDLs, HDLs

Derived Lipids
Fatty acids - palmitic acid, oleic acid, stearic acid, linoleic acid
Steroids - Cholesterol, ergosterol, cortisol, bile acids, Vitamin D, estrogens,
androgens
Hydrocarbons- Terpene
 DERIVED LIPIDS STEROIDS
FATTY ACIDS
 SIMPLE LIPIDS
Typical triacylgycerols Waxes
 COMPOUND LIPIDS
PHOSPHOLIPID GLYCOLIPIDS

LIPOPROTEIN
FOUR IMPORTANT FUNCTIONS OF LIPID IN THE BODY:

Energy source and reserve – Fat provides 80-90 % of the energy requirement at rest. One
gram of pure lipid contains about 9 calories of energy, more than twice the energy available
from carbohydrate or protein.

Protection of vital organs– The body’s internal fat (about 4 % of the total) protects against
trauma to vital organs like the heart, liver, kidneys, spleen, brain, and spinal cord.

Thermal insulation–Fat keeps us warm!

Vitamin carrier and hunger suppressor–Approximately 20g of daily dietary fat provides a
sufficient source and transport medium for the four fat-soluble vitamins: A, D, E, and K.
Severely reducing lipid intake depresses the body’s level of these vitamins and may lead to a
deficiency.
Major roles of lipid in cell structure and metabolism:

triacylglycerols: major form of stored energy in mammals

phospholipids, glycolipids, cholesterol: components of cell membranes

cholesterol: precursor of steroid hormones, bile salts and vit. D3

intracellular messengers: prostaglandins, prostacyclins, thromboxanes, leucotrienes, protein

targeting to membranes
United States

The average daily intake of lipids – 65g -

about 90% - TAG (triacylglycerol)

Other lipids present in diet:

- cholesterol
- cholesterol ester
- phospholipids and unesterified
(„free’’) fatty acids

Europe
Belgium and Germany lead the world in the highest amounts of fat consumption, with Belgians
eating 95 grams of fat per day.
These people are far from having the highest obesity rates. In fact, Germany has some of the
skinniest people in the world.
https://www.worldatlas.com/articles/top-fat-consuming-countries-in-the-world.html
 AVERAGE INDIVIDUAL DAILY FAT CONSUMPTION (IN GMS)
1 Belgium 95.00
2 Germany 86.50
3 Finland 80.80
4 Netherlands 80.40
5 Sweden 80.30
6 Saudi Arabia 79.00
7 Spain 78.40
8 Malaysia 78.30
9 France 74.20
10 Switzerland 73.60
LIPIDS DIGESTION
 BILE
Bile is produced in liver, stored in
gallbladder

➢ Alkaline solution composed of:

– Bile salts
– Cholesterol
- Lecithin
– Bilirubin

➢ Bile does not contain digestive

enzymes

➢ Responsible for fat emulsification

- Detergent action
 LIPIDS DIGESTION IN STOMACH
✓ Lingual lipase attacks the 3 or 1–ester bond forming diacyloglicerols and free fatty
acids, aiding emulsification

✓ Secreted by dorsal surface of tongue

✓ Active at low pH (2.0-7.5)

✓ Optimum pH 4.0-4.5 (express higher activity in infant’stomach)

✓ Ideal substrate – short chain TAGs (milk fat)

✓ Short chain fatty acids released are absorbed directly from stomach wall and
enter the portal vein
 LIPIDS DIGESTION IN STOMACH

✓ Gastric lipase - secreted in small quantities

✓ More effective at alkaline pH (average pH 7.8) (express higher activity in

infant stomach)

✓ It requires the presence of Ca2+

✓ Not effective for long chain fatty acids, most effective for short and medium
chain fatty acid

✓ Milk, egg yolk and fats containing short chain fatty acids are suitable substrate
for its action
 LIPIDS DIGESTION IN INTESTINE
Two processes: pancreatic enzymes action
emulsification by bile salts and peristalsis

✓Pancreatic lipase becomes efficient only

in the presence of colipase in the duodenum.
✓convert triglyceride substrates found in ingested
oils to 2-monoglycerides and free fatty acids
✓It is effective for long chain fatty acids
✓Unlike some pancreatic enzymes that are
activated by proteolytic cleavage (e.g.trypsin)
pancreatic lipase is secreted in its final form.

Other pancreatic enzymes:

✓ Phospholipase – A2 acts on phospholipids, it is secreated as a proenzyme
✓ Cholesteryl esterase - acts on cholesteryl esters
Sequence of events in fat digestion
Micelle Formation

•Complex of lipid materials soluble

in water
•Contains bile salts, phospholipids &
cholesterol
•Combines with 2-monoglycerides,
free fatty acids and fat-soluble
vitamins to form mixed micelles
 LIPID ABSORPTION
•Mixed micelles move to intestinal mucosal cells (enterocytes) and release contents near cell

•The bile salts are re-absorbed further down the gastrointestinal tract (in the ileum),
transported to the liver, and finally recycled and secreted back into the digestive tract
 Lipid absorption
Long fatty acids, 2-monoglycerides (2-MAG), cholesterol, and cholesterol esters move down
concentration gradient (passive diffusion).

Glycerol and short chain fatty acids directly enter mesenteric blood.

2-MAG and longer-chain FA reformed into triglycerides, and then packaged with protein and
phospholipids form chylomicrons

Cholesterol is reformed into cholesterol ester and packaged into chylomicron

1. Acyl CoA monoacylglycerol
1 acyltransferase

2. Fatty acyl-CoA synthetase

2
3. Acyl CoA:cholesterol
3 acyltransferase (ACAT)
Chylomicrons are absorbed from enterocytes into lymph vessels and finally
enter blood via thoracic duct

Chylomicrons pick up apo C II, III and apo E from HDL and become mature
chylomicron

MATURE CHYLOMICRON

/E
 Metabolism of chylomicrons
lymph

Blood
(mature chylomicron)

LPL irecognizes apoC on chylomicrons

It is located on the walls of blood capilllaries, anchored to the endothelium by

negatively charged proteoglycan chains of heparan sulfate
Familial LPL deficiency - type I hyperlipoproteinamia
(prevelance 1:10.000), sever cases, the hypertriglyceridemia can reach a level 1000mg/dL
 TAG in chylomicrons are degraded to free fatty acids (FFA) and
glicerol by LPL

! LPL is activated by insulin (only in adipose tissue)

! LPL is activated by heparin

The free fatty acids may directly enter the muscle cells or adipocytes or be transported in the
blood in association with serum albumin until they are taken up by cells (except red blood
cells and brain)

Glycerol is taken up by liver, kidney or mammary gland (during lactation) from the blood and
phosphorylated by glycerol kinase to produce glycerol 3 - phosphate
 lymph

Blood
(mature chylomicron)

chylomicron "remnants" are taken up by liver in endocytosis; contain small amounts of

TAGs and cholesterol
PART 1: LIPIDS CLASSIFICATION, DIGESTION & ABSORPTION - YOUR „EXIT TICKET”
Lipids classification-
Simple lipids: TAG and waxes (general structure)
FA: saturated (palimitic and stearic) – general structure
unsaturated ( 3 &  6), which are essential?
Steroids:cholesterol (general strucutre)
Complex lipdis - examples

The main functions of TAG,

FA cholesterol and complex
lipids

Lipids digestion: tissue, enzymes plus the

main products of lipids digestion
Bile - function in lipids digestion
 LIPID METABOLISM IN THE FED STATE -
overview
Blood: the high level of chylmicrons

Adipose tissue:
- insulin activates LPL
- insulin activates GLUT 4 and adipocytes uptake Glc. Glc enters glycolysis pathway and is
converted to DHAP
- adipocytes uptake FA
- Insulin stimulates synthesis of TAG

Liver:
- uptakes glicerol (product of lipolysis in chylomicron)
- synthesizes FA
- synthesizes TAG
 FATTY ACIDS SYNTHESIS

Metabolic state: fed state, in the presence of insulin

Tissue localization: mainly in the liver, additionally in mammary gland during lactation, in the
lesser extent in adipose tissue

Cellular localization: cytosol

Substrates and cofactors: acetyl-CoA (product of pyruvate oxidative decarboxylation),

NADPH (penthose phosphate pathway, malic enzyme)
ATP
biotin, HCO3-
 FATTY ACIDS SYNTHESIS
Fatty acids synthesis occurs primarily in the liver and lactating mammary glands and, to a
lesser extent in adipose tissue.
The first step is the transfer of acetyl-CoA from
mitochondria to the cytosol

Acetyl-CoA is produced by the oxidative

decarboxylation of pyruvate

Acetyl-CoA cannot cross the inner mitochondrial

membrane, it condensates with oxaloacetate to
High citrate and
citrate (citrate synthase)
high ATP

Citrate leaves the mitochondria and is cleaved in

cytosol to produce cytosolic acetyl-CoA
THE FORMATION OF MALONYL~CoA IS THE COMMITTED STEP IN FATTY ACID
SYNTHESIS

Irreversible reaction catalyzed by acetyl~CoA carboxylase (ACC):

acetyl~CoA + ATP + HCO3- malonyl~CoA + ADP + Pi + H+

ACC contains a biotin prosthetic group, and the reaction mechanism is similar to
pyruvate carboxylase and propionyl~CoA carboxylase reactions.
The two steps in the reaction:
Biotin----Enzyme + ATP + HCO3- <===> CO2-Biotin----Enzyme + ADP + Pi

CO2-Biotin----Enzyme + acetyl~CoA malonyl~CoA + Biotin----Enzyme

Acetyl~CoA carboxylase (ACC) precisely is regulated

Short term regulation of ACC:

1. Allosteric regulation
The inactive form of ACC is a dimer
Citrate is allosteric activator and promote polymerization
of ACC to the active form
The long-chain fatty acyl-CoA (the end product of the pathway) is allosteric inactivator which
caused depolymeryzation

2. Reversible phosphorylation/dephosphorylation –
after hormons (insulin or epinephrine) action
 Acetyl~CoA carboxylase (ACC) precisely is regulated

Long- term regulation of ACC:

1.Type of Diet: High-calorie, high carbohydrate increase synthesis of ACC

low – calorie, high-fat diet decrease synthesis of ACC
2. Synthesis of ACC is upregulated by insulin via sterol regulatory element -
binding protein (SREBP-1)
[c] Fatty acids
[c] Fatty acids

https://en.wikipedia.org/wiki/Sterol_regulatory_element-binding_protein
 FATTY ACIDS SYNTHASE COMPLEX (FAS) – multifunctional enzyme
in eucaryotes

ketoacyl-ACP synthase
palmitoyl thioesterase
malonyl/acetyl-CoA enoyl-ACP reductase
ACP transacylase
ketoacyl-ACP reductase
hydroxyacyl-ACP dehydratase

▪ It is a multienzyme complex
▪ FAS is a dimer composed of two identical subunits (monomer)
▪ Each subunit contains the activities of 7 enzymes and an ACP (acyl carrier protein) with 4-
phosphopantetheine SH group and Cys with SH group
▪ The two subunits lie in antiparallel (head to tail ) orientation
 Reactions catalyzed by fatty acid synthase

ATP-dependent carboxylation
Acetyl CoA-ACP provides energy input.
acetyltransacylase Malonyl CoA-ACP
transacylase
3-ketoacyl-ACP reductase
The CO2 is lost later during
condensation with the growing
fatty acid.
3-ketoacyl-ACP synthase
3-hydroxyacyl ACP „condensing enzyme”
dehydratase

The spontaneous decarboxylation

drives the condensation reaction.

Enoyl-ACP reductase
Product release:

The thioesterase domain catalyzes the release of the end product

palmitic acid (16C).

Summary (ignoring H+ & water):

acetyl~CoA + 7 malonyl~CoA + 14 NADPH palmitate + 7 CO2 + 14 NADP+ + 8 CoA

Accounting for ATP-dependent synthesis of malonate:

8 acetyl~CoA + 14 NADPH + 7 ATP palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi
The elongation and desaturation of fatty acids are accomplished by additional
enzyme systems

Elongases are present on the cytosolic face of the ER.

Desaturases are mainly in the ER membrane. Mammals cannot introduce

double bonds beyond C10, thus linoleic and linolenic acids are essential fatty
acids.
15 12 9

Linolenic acid (ω-3)

12 9

Linoleic acid (ω-6)

ELONGATION OF FATTY ACIDS
Most fatty acids can be synthesized from
palmitate.

Palimitate can be elongated by addition of two-

carbons units to the carboxylate end of palmitate

Malonyl CoA is the two carbon donor, and

NADPH supplies the electrons

The brain has additional elongation capabilities,

allowing it to produce the very long chain fatty
acids over 22 carbons that are required for
synthesis of brain lipids
 DESATURATION OF FATTY ACIDS
Desaturases are present in the smooth endoplasmic reticulum, they add cis double bond.

The desaturation reactions require O2, NADH, cytochrome b5, and its FAD linked reductase.

The first double bond is typically inserted between carbons 9 and 10, producing primarily oleic
acid 18:1 (9), and small amount of palmitoleic acid 16:1 (9)

Human have carbon 9,6,5 and 4 desaturases but lack the ability to introduce double bond
from C10 to the ω end of the chain, thus polyunsaturated acid ω – 6 linoleic and ω-3 linolenic
acid are essential

It can be synthesized
form linoleic acid
POLYUNSATURATED FATTY ACIDS
DESATURATION
 TAG synthesis
TAG are synthesized in
- adipose tissue
- liver
- mammary gland during lactation.
Triacylglycerols, stored in adipose cells (white adipose
tissue), are the major energy reserve

https://www.dreamstime.com/stock-photos-adipocyte-structure-fat-cell-responsible-
accumulation-energy-obesity-weight-gain-weight-loss-vector-diagram-image40078733

Fats provide about 6 times the energy/mass of carbohydrates

Stored in an anhydrous state
 ADIPOSE TISSUE
IN MAMMALS, TWO TYPES OF ADIPOSE TISSUE EXIST:
 Different location of BAT and WAT at different ages.

Brown adipose tissue (BAT) in infants and young adults had been described to be localized mainly in the cervical-
supraclavicular region as well as in periaortic areas inside the thorax and the abdomen, and in particular in the
perirenal fat. With aging the amount of detectable BAT decreases progressively and it remains represented mainly in
the supraclavicular and perirenal sites.
 TRIACYLGLYCEROL SYNTHESIS
The glycerol of TAG is derived from glicerol-3-phosphate
(initial acceptor)

In the liver/mammary gland glycerol kinase is present but adipose

tissue lacks glycerol kinase activity.

In adipose tissue glycerol-3-P is generated from the glycolytic

intermediate, dihydroxyacetone phosphate (DHAP)
Mammary gland

The source of glycerol-3-P is different in these tissues!!!!

 TRIACYLGLYCEROL SYNTHESIS
adipose tissue obtains FA from the action of LPL on chylomicron triglycerides
FA are transported into the cell, mainly by facilitated diffusion, and are activated to acylCoA
before they can be used for TAG synthesis.

Liver uses mainly endogenous FA

The three fatty acids esterified to glycerol to form

a TAG are usually not of the same type.

saturated fatty acid (carbon 1)

typically unsaturated fatty acid (carbon 2)

Saturated or unsaturated fatty acid (carbon 3)

 TRIACYLGLYCEROL SYNTHESIS

Dihydroxyacetone
phosphate Glycerol phosphate dehydrogenase
NADH H+ This is the same enzyme that
participates in the glicerol
NAD+ phosphate shuttle and
gluconeogenesis from glycerol

Phospholipids

TAG are stored in

adipose cells
PART 1: LIPIDS METABOLISM in THE FED STATE - YOUR „EXIT TICKET”
LPL - tissue localisation, activity,
reaction, substrates & products

Adipose tissue metabolism

in the fed state: TAG
synthesis, Insulin action in Understanding the main
adipose tissue differences between liver and adipose
tissue TAG synthesis
Liver metabolism in the fed state: FA
synthesis and TAG synthesis, VLDL
formation
 LIPID METABOLISM DURING FASTING

BLOOD: higher level of VLDL and FFA

ADIPOSE TISSUE: TAG are hydrolysed to Glicerol and FA (lipolysis)

ALL CELLS EXCEPT RBC AND BRAIN: beta oxidation (fatty acid
catabolism)

LIVER: beta oxidation, during prolong fasting ketogenesis

 STORAGE OF FATTY ACIDS AS COMPONENTS OF
TRIACYLGLYCEROLS (TAG)
Adipose tissue is specialized for the storage of fat (TAG)

Triglyceride is the most suitable storage form of energy because of its high energy density

Fat can be stored without accompanying water, whereas each gram of glycogen binds 2 g of
water. Therefore, the energy value of 15 kg of fat is equivalent to 100 kg of hydrated
glycogen

Using fat for energy (lipolysis)

•Hormone-sensitive lipase (in adipose tissue)
•Provides very little glucose (from glycerol)
 Epinephrine -
action
The ABSENCE OF
INSULIN
adipose triglyceride lipase (AGTL)
hormone sensitive lipase (HSL)
monoacylglycerol lipase (MGL)
Perilipin (Peri A)

http://med.monash.edu/physiology/research/bolm.html

AGTL is highly expressed in white adipose tissue with less epinephrine

expression in skeletal muscle, accounts for 60-70% of
triglyceride lipase activity in adipose and appears to be Perilipin A – it is protein which coated fat droplets, it limits
essential for the control of normal weight access of HSL, Phosphorylation of Peri A by PKA allows
translocation and binding of HSL to the droplet
INSULIN ACTION IN ADIPOSE TISSUE

Decreasing activity of PKA

 FAT METABOLISM IN ADIPOSE TISSUE IS
UNDER HORMONAL REGULATION
NOREPINEPHRINE /EPINEHRINE – released during physical exercise and stress, stimulate
lipolysis through b receptor and cAMP , activation PKA which phosphorylates both perilipin A
and lipase

INSULIN – high insulin level signals the abundance of dietary nutrients that are used for
storage/low insulin level signals a shortage of nutrients during fasting and a need for fat
breakdown.
A major effect of insulin on adipose tissue is the inhibition of lipase, insulin
activates cAMP-degrading phosphodiesterase; insulin increases uptake of glucose into the cell
(activation of GLUT4); insulin stimulates of LPL in capillaries of adipose tissue and induces of
glicerol phosphate-acyl transferase (enzyme that adds the first fatty acid to glicerol 3
phosphate)

GLUCOCORTICOIDS/GROWTH HORMONE AND THYROID HORMONE – induce lipolysis by

inducing the synthesis of lipolytic proteins
 Intracellular accumulation of fats leads to insulin resistance in skeletal muscle

DYSREGULATION OF FATTY ACID

METABOLISM IN OBESITY
LEAN: FA derived from adipose tissue
lipolysis and dietary intake are transported
across the plasma membrane. The
majority of FA are directed towards β-
oxidation and are completely oxidized. A
smaller fraction of the FA are esterified to
form DAG and TAG and some fatty acids
are converted into ceramide.

OBESE: Increased lipolysis from an

enlarged adipose mass increases FA
delivery to peripheral tissues. FA uptake is
greater and an increased fraction of the
transported fatty acids are directed towards
esterification, rather than oxidation.
Accordingly, lipid metabolites accumulate
http://med.monash.edu/physiology/research/bolm.html in the tissue.
ADIPOSE RELEASED FACTORS INDUCE INSULIN RESISTANCE IN
SKELETAL MUSCLE
In obesity and type 2 diabetes there is an accelerated release of adipokines
that are known to induce insulin resistance including TNF α, resistin, retinol-
binding protein 4, plasminogen activated inhibitory 1 (PAI-1) and visfatin.
Conversely, adiponectin, which is the only adipocyte hormone known to
induce insulin sensitivity, is decreased.
In this way, obesity is associated with a chronic low grade inflammatory state
that contributes to insulin resistance.
 MOBILZATION OF STORED FATS AND OXIDATION OF FATTY
ACIDS
After lipolysis , the free (unesterified) fatty acids move through the cell
membrane of the adipocyte and bind to plasma albumin.

They are transported to the tissue, enter cells, get activated to acyl-CoA,

Then fatty acids are oxidized for energy in mitochondria. The major pathway for catabolism of
fatty acids is mitochondrial beta - oxidation
CARNITINE CARRIES LONG-CHAIN ACTIVATED FATTY ACIDS INTO THE
MITOCHONDRIAL MATRIX
 CARNITINE SHUTTLE
Medium chain (C8-C12) and short (<C8) FA do not require carnitine to enter the mitochondrion.
Carnitine can be obtained from diet (meat products), or can be also synthesized from Lys and Met (liver an
kidney).
Muscle and heart are totally dependent on uptake of endogenous carnitine or of the diet
Diseases of carnitine synthesis, transferase, or translocase: range from muscle cramping to severe weaknes
and death – Muscle, kidney, and heart primarily affected.
Acetyl~CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation

1. Acyl~CoA dehydrogenase (AD)

(4 different) formation of trans ab double
bond

2.enoyl hydratase (EH) hydration of trans

double bond to form 3-L-hydroxyacyl-CoA
(cis->D)

3. 3-L-hydroxyacyl-CoA dehydrogenase
(HAD) oxidation to the b-keto

4.ketoacyl thiolase (KT) cleavage of the ab

bond to release acetyl-CoA and shortened
acyl-CoA
The complete oxidation of stearic acid yeilds ~146 molecules of ATP
Stearyl~CoA is C18-acyl~CoA
 Certain fatty acids require additional steps/enzymes for degradation
UNSATURATED FATTY ACIDS.
Two additional enzymes an isomerase and a reductase are needed 9
1. 3,2-enoyl~CoA isomerase creates substrate for enoyl hydratase
2. 2,4 dienoyl CoA reductase (NADPH – dependent) 18:1 (9)

It provides less energy because unsaturated acids are less reduced

12 9

18:2 (9,12)
ODD CHAIN FATTY ACIDS
yeild propionyl~CoA, which is converted into succinyl~CoA in a reaction that requires
biotin and vitamin B12
 Certain fatty acids require additional steps for degradation
Branched chain fatty acids with the branch at odd-number carbons undergo a oxidation

a oxidation
PHYTANIC ACID -
Product of chlorophyll
metabolism
 Certain fatty acids require additional steps for degradation

Very long chain fatty acids 20C long or longer, undergo a

preliminary b oxidation in peroxisome.

The shortened fatty acids (C8) is transferred to a

mitochondrion for further oxidation.

The initial dehydrogenation in peroxisomes is catalyzed

by an FAD containing acyl CoA oxidase

The FADH2 produced is oxidized by molecular oxygen,

which is reduced to H2O2. The H2O2 is reduced to H2O by
catalase.
 DISORDERS ASSOCIATED WITH IMPAIRED b OXIDATION

Medium chain fatty acyl CoA dehydrogenase (MCAD) – decreased ability to oxidize fatty
acids with 6 to 10 carbons (which accumulate and are present in urine)
Sudden infant death syndrom (SIDS) – unexpected death of healthy infants, usually
overnight
MCAD has been identified as the cause of some reported cases of SIDS
MCAD – the most common inborn errors of metabolism in northwest Europe

Ackee Friut (Bligia Sapida)

Jamaican vomiting Sickness – ingestion of the The Toxic Tree That Tastes Delicious

unripe seeds from the fruit of the Ackee tree,

which contains the toxin hypoglycin, that
inactivates medium and short-chain acyl-CoA
dehydrogenases, inhibiting b oxidation,
thereby causing hypoglycemia.
 KETON BODIES : ALTERNATE FUEL FOR CELLS
Ketone bodies are metabolic fuel under conditions of carbohydrate deficiency

In mammals, there is no pathway for the formation of glucose from acetyl~CoA!!!!

Acetyl~CoA can be oxidized via the cycle as long as sufficient OAA is present.

Between meals or during fasting, gluconeogenesis in the liver produces glucose. This diverts OAA
from the citric acid cycle, and eventually the cycle cannot turn.

The liver convert the excess acetyl CoA from beta oxiadtion to ketone bodies
KETON BODIES : ALTERNATE FUEL FOR CELLS
SYNTHSIS PATHWAY

3-hydroxy-3-methylglutaryl (HMG)-CoA synthase

✓ the rate limiting enzyme of ketogenesis,
✓ synthesis is stimulated by fasting, dietary fat and
insulin deficiency.
✓ Fatty acids are inducer of HMG-CoA synthase
KETON BODIES : ALTERNATE FUEL FOR CELLS
UTYLIZATION

BHB
Metabolic conversion of ketone bodies to acetyl~CoA

The needed enzymes: D-3-hydroxybutyrate

dehydrogenase, 3-ketoacyl CoA transferase,
acetoacetyl CoA thiolase

Liver lacks the 3-ketoacyl-CoA transferase, and

thus does not use the ketone bodies it
produces
 KETON BODIES : ALTERNATE FUEL FOR CELLS
The skeletal muscle, heart muscle, kidney, and brain switch from using glucose as
the main energy source to using ketone bodies during prolonged fasting.

Heart muscle and renal cortex use acetoacetate in preference to glucose.

The brain has an enormous need for respiratory fuel, each day requiring
approximately 140g of glucose, which is equivalent to nearly 600kcal (brain can
not use fatty acids as a fuel). To stay alive , the brain must be suplied with
respiratory fuel at all time. The brain efficiently oxidized acetoacetate
and 3 hydroxybutyrate.

Red blood cells can not use a ketone bodies,

because of lack mitochondria
KETOGENESIS IN DIABETES MELLITUS (type 1)

KETONEMIA – HIGH [C] OF KETON BODIES IN BLOOD

KETONURIA - HIGH [C] OF KETON BODIES IN URINE

 EXOGENOUS KETONES HAVE BECOME A POPULAR NUTRITIONAL SUPPLEMENT SINCE
THEIR INTRODUCTION IN 2014.
Most supplements rely on BHB as the source of their exogenous ketone
bodies.

They raise blood ketones even if you’re not in a state of ketosis before ingestion (such as
when not on a low carb diet). Exogenous ketone supplementation has a
promising outlook for enhancing athletic
performance for a variety of reasons. Firstly,
ingested ketone bodies induce an acute ketosis that
lasts for several hours and mimics the physiology of
starvation.
Secondly, exogenous ketones present a way to
elevate ketone levels without having depleted
muscle glycogen stores (low muscle glycogen is
well known to impair sustained physical
performance)

Pinckaers PJ, Churchward-Venne TA, Bailey D, van Loon LJ. Ketone Bodies and Exercise
Performance: The Next Magic Bullet or Merely Hype?. Sports Med. 2017;47(3):383-391.
doi:10.1007/s40279-016-0577-y
PART 3: LIPIDS METABOLISM IN FASTING STATE - YOUR „EXIT TICKET”

Adipose tissue: lipolsysis, enzymes,

products, hormonal regulation

Liver metabolism during

fasting,

The odd chain FA catabolism

FA catabolism (beta oxidation): and unsaturated FA
activation, carnitin function, types of catabolism – general
reaction during beta oxidation inforamtion
 EICOSANOIDS
Any of the following FA can be used as a precursor of eicosanoids , but
arachidonic acid is most important simply because it is a far more abundant than
others
Arachidonic acid pathway
Synthesis of prostaglandins, prostacyclins, tromboxanes and leukotrienes

Must first be released from membrane phospholipids, via activation of cellular phospholipases
Prostaglandins, thromboxanes and leukorienes are extremely potent compounds that show a
wide range of responses both physiologic (inflammatory response) and pathologic
(hypersensitivity).
They ensure gastric integrity and renal function, regulate smooth muscle contraction (intestine
and uterus are key sites) and blood vessels diameter, and maintain platelet homeostasis.
Aspirin and other non-steroid anti-inflammatory drugs inhibit
cyclooxygenase
PART 3: LIPIDS METABOLISM IN FASTING STATE - YOUR „EXIT TICKET”

eicosanoids – types, the main function

Synthesis – only the step with

COX

COX1, COX2 and COX 3 – when?

Wher? And functions
 Acetyl~CoA – its central position in the metabolism

https://pl.pinterest.com/pin/565905509412197751/
Acetyl~CoA – its central position in the metabolism
CARBOHYDRATES
GLUCOSE LIPIDS

cholesterol

PROTEINS
Thank you
COMPARISON OF FATTY ACID Β-OXIDATION AND FATTY ACID
BIOSYNTHESIS
Acetyl~CoA – its central position in the metabolism

PLANTS

PLANTS

Vit D3
THE OXIDATION OF UNSATURATED FATTY ACIDS
In the oxidation of unsaturated fatty
acids, most of the reactions are the same
as those for saturated fatty acids,

Two additional enzymes an isomerase

and a reductase are needed
1. 3,2-enoyl~CoA isomerase creates
substrate for enoyl hydratase
2. 2,4 dienoyl CoA reductase (NADPH
– dependent)
It provides less energy because unsaturated
acids are less reduced, therefore fewer
reducing equivalents can be produced from
these structure