Solomon, Marc Ralph M.

2015-48305
Biochem 35 WORKSHEET 4
3. How much energy is expended in the
Lipid Anabolism synthesis of palmitate from acetyl CoA
1. Why is the carrier of the fatty acyl group ACP (include the moles ATP lost in catabolism of
rather than CoASH? What advantage will glucose in the hexose monophosphate
ACP have over CoASH as a carrier of the shunt)? What will be the net ATP gain in
fatty acyl group? the catabolism of the palmitate that is
mobilized from storage?
Both ACP and CoASH have 4’-
(HMS)
phosphopantetheine as their substrate- 1ATP 2NADPH
binding site. Despite this similarity, the (acetyl CoA to pamitate)
enzymes of fatty acid synthesis show a 14 NADPH=7ATP
striking degree of substrate specificity in that 7ATP
these enzymes require thioesters of ACP as TOTAL=14ATP
substrates and they use thioesters of CoASH
poorly or not at all (Majerus, 1967). This is 8acetyl CoAx10=80ATP
because CoASH is not bound since it is 7 cycles of B-oxid 7 NADH(2.5) +
esterified to AMP, while ACP is bound to a 7FADH2(1.5) 28ATP
multifunctional protein. With this, ACP can -2ATP(for activation and transpo)
transport the growing fatty acid chain more
=106ATP
efficiently between enzyme domains of the
fatty acid synthase during biosynthesis
(Nguyen, et al., 2014).
4. How many palmitate can be produced from
2. Give the Cleland diagram of the 4 reactions the excess intake of 100 moles maltose
for fatty acid synthesis in the cytoplasm. (assuming that only 10% is catabolized; and
absorption is 100%).

100 mol Maltose x (2 glucose units per

maltose) = 200 glucose

90% = 180 mol glucose = 360 mol acetyl CoA

360 acetyl CoA x (1 palmitate/ 8 acetyl CoA)

= 45 mol palmitate

5. Give the mechanism catalyzed by a)

elongases and b) desaturases.
Elongases
Desaturases
6. What are the essential fatty acids? Why are
they essential and have to be taken in the
diet?
The essential fatty acids are ω-6-linoleic acid
(LA) and ω-3-linoleic acid (ALA). These fatty
acids are involved in various biological
processes and produce many compounds
when they are metabolized. However, our
body lacks the ability to introduce double
bonds in fatty acids beyond carbon 9 and 10,
thus, it they must be taken in our diet
(Kapalka, 2010).
7. When are triacylglycerols synthesized?
Why?
Hepatic triglyceride synthesis could be
driven by substrate, independent of
changes in hepatic insulin signaling.
Triacylglycerol synthesis is driven by high
influx of fatty acid which are not inhibited to
be catabolized intro ketone bodies.
8. Why are TAGs the main storage form of
glucose?
When carbohydrates are ingested in excess
of the organism’s capacity to store
glycogen, the excess is converted to TAGs
which have the highest energy content of all
stored nutrients (38 kJ/g) due to the amount
of highly reduced carbons. (Nelson and
Cox, year; Garrett and Grisham, year)
9. Show the mechanism and Cleland diagram
for the synthesis of 1-linoleyl-2-arachidyl-3-
heptanoyl glyceride
10. Show the mechanism and Cleland diagram
of the overall reaction for the synthesis of
a. phosphatidyl ethanolamine (students
with surnames Q-Z)
11. What regulates triacylglycerol synthesis vis
a vis phospholipid synthesis. Which step in
the common pathway can this regulation be
effected?
The biosynthesis of triacylglycerol is regulated in
three ways: glycerol 3-P and diacylclycerol
acyltransferases are hormonally controlled by
phosphorylation-dephosphorylation mechanisms,
insulin increases supply of glycerol 3-P and leptin is
secreted during lipogenesis consequently
diminishing the release of neuropeptide Y which is
responsible for the release of insulin and
glucocorticoids. The synthesis of triacylglycerols
and phospholipids proceed through a common
intermediate: phosphatidic acid (Coleman & Lee,
2004).
Lipid Anabolism II
1. Give 3 processes that show the involvement
of an eicosanoid and how these
metabolite(s) mediate the reaction.
FORMATION OF THROMBOXANE
-thromboxanes are produced by platelets.
They stimulate vasoconstriction and platelet
aggregation, which helps to iniitate blood
clotting.
FORMATION OF PROSCYCLINS
-prostacyclins are predominantly
synthesized by endothelial cells and elicit
the opposite effects of thromboxanes.
FORMATION OF PROSTAGLANDINS
-they aid inflammatory responses, pain and
fever, regulation of blood pressure, and
gastrointestinal lining protection.
2. Show the mechanism for the synthesis of
any of the group (group 1, 2 or 3, PGE,
PGD, or PGF) of prostaglandins in the
figure shown above.
5. Show the mechanism for the synthesis of
3. Discuss why colds or any upper respiratory
infection can trigger leukotriene synthesis
and asthmatic attacks.
Leukotrienes are inflammatory chemical that
are released in the presence of allergens.
With this, colds is caused by allergens.
6. Discuss at least one (1) function of
Production of leukotrienes causes
production of excess amounts of fluids and
mucus which result to tightening of airway
muscles; thus, triggering asthma attacks.
4. How is cholesterol synthesis regulated?
Cholesterol synthesis is regulated in a
number of ways. First is by control of HMG-
CoA reductase that catalyzes the rate-
limiting step of cholesterol synthesis. HMG-
CoA reductase synthesis is controlled by
sterol regulatory element binding protein
(SREBP), which binds to the sterol
regulatory element (SRE) on the reductase
gene; thus, inducing the gene’s
transcription. SREBP, in its inactive form, is
associated with SREBP cleavage activating
protein (SCAP) in the endoplasmic
reticulum. SCAP is able to bind to
cholesterol and induces it to bind to another
protein; thus, inhibiting the release of
SREBP thereby inhibiting HMG-CoA
reductase gene transcription and
translation. Hence, cholesterol synthesis is
seized due to the decrease in the enzyme
that catalyzes the rate limiting step.
Nonsterol derivatives of mevalonate can
also inhibit reductase mRNA translation. On
the other hand, when cholesterol level is
low, SCAP delivers the SREBP to the golgi
apparatus and releases it to induce the
SREBP binding to the HMG CoA reductase
gene; thus, promoting its transcription and
translation.
The HMG CoA reductase have a domain
that senses signals that induces
degradation. Presence of high amounts of
sterols induces binding of proteins that
promotes it degradation; thus, inhibiting
cholesterol synthesis. Moreover, high AMP
levels drives a protein kinase to
phosphorylate the reductase, which in turn
decreases its activity; thus, inhibiting
cholesterol synthesis.
any of the following: Vit. D, sex hormones or
bile salts, from cholesterol.
cholesterol or its derivative and the
mechanism it mediates.
Estrogen mediates breast development
during puberty, breast maturation during
pregnancy in preparation of lactation and
breastfeeding. It is responsible for inducing
the ductal component of breast
development and causing fat deposition and
connective tissue growth.
Lipid Catabolism
1. What reaction(s) commit(s) fatty acids to
catabolism, specifically, - oxidation? Why
will the reaction commit fatty acids to
complete oxidation?
The reactions involved in the acyl carnitine shuttle
(formation of an activated fatty acyl AMP
intermediate, attack of the thio sulfur of CoA on the
carbonyl carbon producing fatty acyl CoA, carnitine
replacing CoASH as carrier, then the replacement
of carnitine with CoASH) are the committed steps in
the catabolism of fatty acids. This commits fatty
acids to oxidation as this will transport the fatty
acids into the mitochondria where beta oxidation
takes place.
2. Why does -oxidation occur in the
mitochondria? What regulatory advantage
would this compartmentation have on the
metabolism of fats?
Beta-oxidation occurs in the mitochondria because
the enzymes necessary for the breakdown of fatty
acids are found here. On the other hand, synthesis
of fatty acids occurs in the cytosol. This
compartmentation ensures that no interference and
competition occurs between the two processes.
3. What drives the transport of fatty acids to
the mitochondria? Why?
Transport of fatty acids from the cytoplasm to
the mitochondrial matrix for oxidation. Following
activation to acyl-CoA, CoA is exchanged for
carnitine by carnitine palmityl transferase (CPT-
I), which is then transported to the inside of the
mitochondria where a reversal exchange takes
place through the action of carnitine
acylcarnitine translocase (CPT-II), and beta-
oxidation machinery initiates its activity,
producing reducing equivalents that feed the
electron transport chain.
4. Give the Cleland diagram of the 4 reactions
in - oxidation in the mitochondrial matrix.
5. While catabolism of fats provides more
energy, it is not the primary source of
energy of cells. Why is this so? Compare
the amount of energy that can be obtained
from 3 glucose units, stearic acid, oleic acid
and pentadecanoic acid.
6. Compare the amount of acetyl CoA that can
be obtained from no. 4? How many ketone
bodies (acetoacetate and acetone) can be
produced from each of these energy
sources (glucose, stearic acid, oleic acid
and nonadecanoic acid).
Ketogenesis
1. When are ketone bodies synthesized?
Explain briefly.
Primarily, synthesis of ketone bodies happens
when the cells are starved, or there is an
impairment in glucose metabolism. These ketone
bodies serve as alternative source of energy in
case such event takes place.
2. What organs utilize ketone bodies? Explain.
Brain: The brain utilizes ketone bodies in the event
that glucose concentration is depleted (e.g.
starvation). The brain only uses glucose as primary
source of energy, but in the event that the levels
drop significantly, the demand for ketone bodies
increases.
Heart: The heart prefers to utilize fatty acids as
source of energy. At ketotic conditions, i.e. fatty
acid are broken down into ketone bodies, the heart
utilizes them.
3. How is ketone body synthesis regulated?
Why?
Synthesis of ketone bodies is dependent on the
activity of three enzymes: triglyceride lipase, acetyl-
CoA carboxylase, HMG CoA synthase. These
enzymes are controlled by levels of circulating
insulin, which slows down ketogenesis, and
glucagon, which promotes ketogenesis.
Release of insulin promotes fatty acyl synthesis via
inhibitory dephosphorylation of triglyceride lipase.
Inhibition of triglyceride lipase prevents break down
of triacylglycerols. Dephosphorylation of acetyl-
CoA carboxylase, on the other hand, activates the
enzymes, and subsequently increases production
of malonyl-CoA, therefore promoting fatty acyl
synthesis instead of ketogenesis.
However, glucagon does the opposite mechanism
of insulin. Ketogenesis is much promoted by
glucagon via phosphorylation of triglyceride lipase
and acetyl-CoA carboxylase produces activating
and inhibiting effect respectively. Finally, the HMG
CoA synthase activity is increased upon starvation
and is also decreased by insulin.
References
Majerus, P. W. (1967). Acyl carrier protein:
Structural requirements for function in fatty acid
biosynthesis. The Journal of Biological Chemistry,
242(10), 2325-2332. Retrieved from
http://www.jbc.org/content/242/10/2325.full.pdf
Nguyen, C., et al. (2014). Trapping the dynamic acyl
carrier protein in fatty acid biosynthesis. Nature,
05(7483): 427–431. DOI: 10.1038/nature12810
Kapalka, G. M. (2010). Substances involved in
neurotransmission. Nutritional and Herbal Therapies
for Children and Adolescents, 4, 71-99. DOI:
.1016/B978-0-12-374927-7.00004-2

4. What is the committed step in ketogenesis?

The committed step in ketogenesis is the
conversion of 3 Acetyl-CoA to b-hydroxymethyl
glutarate.

5. Alcoholism and diabetes can both result in

increased ketone body production. Explain
why and show the mechanism for the
synthesis of ketone bodies from ethanol.
The lack of insulin brought by diabetes type 1
prevents utilization of glucose in the blood. With
this condition, glucose cannot be broken down as
source of energy. The body then resorts to fatty
acyls stores, and therefore it is broken down to
ketone bodies to produce energy. The resulting
condition increase concentration of ketones in the
body, leading to smell akin to a nail polish remover.
On the other hand, high levels of ethanol due to
alcoholism depletes levels of oxaloacetate,
subsequently inhibits gluconeoenesis. The excess
ethanol can also be converted to ketone bodies via
series of redox reactions.