Carnitine palmitoyl transferase I

Carnitine palmitoyltransferase I (CPT1 ) also known
as carnitine acyltransferase I, CPTI , CAT1 ,
CoA:carnitine acyl transferase (CCAT) , or
palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl
carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine . The product is often
Palmitoylcarnitine (thus the name), but other fatty acids may also be substrates.  It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent
movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria. Three
isoforms of CPT1 are currently known: CPT1A,
CPT1B, and CPT1C. CPT1 is associated with the
outer mitochondrial membrane . This enzyme can be
inhibited by malonyl CoA, the first committed intermediate produced during fatty acid synthesis.
Its role in fatty acid metabolism makes CPT1 important in many metabolic disorders such as
diabetes. Since its crystal structure is not known, its exact mechanism of action remains to be determined.

Structure

CPT1 is an integral membrane protein that
associates with the mitochondrial outer membrane
through transmembrane regions in the peptide
chain. Both the N- and C-terminal domains are
exposed to the cytosolic side of the membrane. Three isoforms of CPT1 exist in mammalian
tissues. The liver isoform (CPT1A or CPTI-L) is
found throughout the body on the mitochondria of all
cells except for skeletal muscle cells and white and
brown adipose cells. The muscle isoform (CPT1B or
CPTI-M) is highly expressed in heart and skeletal
muscle cells and white and brown adipose cells.  A third isoform, the brain isoform (CPT1C), was
isolated in 2002. It is expressed predominantly in the brain and testes. Little is known about CPT1C.
The exact structure of any of the CPT1 isoforms has not yet been determined, although a variety of
in silico models for CPT1 have been created based on closely related carnitine acyltransferases, such
as carnitine acetyltransferase (CRAT) An important structural difference between CPT1 and CPT2, CRAT and carnitine octanoyltransferase
(COT) is that CPT1 contains an additional domain at its N-terminal consisting of about 160 amino acids.
It has been determined that this additional N-terminal domain is important for the key inhibitory
molecule of CPT1, malonyl-CoA.
Two distinct binding sites have been proposed to exist in CPT1A and CPT1B. The “A site” or “CoA
site” appears to bind both malonyl-CoA and palmitoyl-CoA , as well as other molecules containing coenzyme A , suggesting that the enzyme binds these molecules via interaction with the
coenzyme A moiety. It has been suggested that malonyl-CoA may behave as a competitive inhibitor
of CPT1A at this site. A second “O site” has been proposed to bind malonyl-CoA more tightly than the
A site. Unlike the A site, the O site binds to malonyl-CoA via the dicarbonyl group of the
malonate moiety of malonyl-CoA. The binding of malonyl-CoA to either the A and O sites inhibits the
action of CPT1A by excluding the binding of carnitine to CPT1A. Since a crystal structure of
CTP1A has yet to be isolated and imaged, its exact structure remains to be elucidated.

Enzyme mechanism

Because crystal structure data is currently unavailable, the exact mechanism of CPT1 is not currently known. A couple different possible mechanisms for CPT1 have been postulated, both of which include the histidine residue 473 as the key catalytic residue. One such mechanism based upon a carnitine acetyltransferase model is shown below in which the His 473 deprotonates carnitine while a nearby serine residue stabilizes the tetrahedral oxyanion intermediate.
A different mechanism has been proposed that suggests that a catalytic triad composed of residues Cys-305, His-473, and Asp-454 carries out the acyl-transferring step of catalysis . This catalytic mechanism involves the formation of a thioacyl-enzyme covalent intermediate with Cys-305.

Biological function

The carnitine palmitoyltransferase system is an essential step in the beta-oxidation of long chain
fatty acids . This transfer system is necessary because, while fatty acids are activated (in the form
of a thioester linkage to coenzyme A) on the outer mitochondrial membrane, the activated fatty acids
must be oxidized within the mitochondrial matrix.
Long chain fatty acids such as palmitoyl-CoA, unlike short- and medium-chain fatty acids, cannot freely diffuse through the mitochondrial inner membrane , and require a shuttle system to be transported to the mitochondrial matrix.
Carnitine palmitoyltransferase I is the first component and rate-limiting step of the carnitine palmitoyltransferase system, catalyzing the transfer of the acyl group from coenzyme A to carnitine to form palmitoylcarnitine. A translocase then shuttles the acyl carnitine across the inner mitochondrial membrane where it is converted back into palmitoyl-CoA.
By acting as an acyl group acceptor, carnitine may also play the role of regulating the intracellular CoA:acyl-CoA ratio

Regulation

CPT1 is inhibited by malonyl-CoA, although the exact mechanism of inhibition remains unknown.
The CPT1 skeletal muscle and heart isoform, CPT1B, has been shown to be 30-100-fold more sensitive to malonyl-CoA inhibition than CPT1A.
This inhibition is a good target for future attempts to regulate CPT1 for the treatment of metabolic
disorders.
Acetyl-CoA carboxylase (ACC), the enzyme that
catalyzes the formation of malonyl-CoA from acetyl-CoA , is important in the regulation of fatty acid metabolism. Scientists have demonstrated that
ACC2 knockout mice have reduced body fat and weight when compared to wild type mice. This is a
result of decreased activity of ACC which causes a subsequent decrease in malonyl-CoA
concentrations. These decreased malonyl-CoA levels in turn prevent inhibition of CPT1, causing an
ultimate increase in fatty acid oxidation. Since heart and skeletal muscle cells have a low capacity
for fatty acid synthesis, ACC may act purely as a regulatory enzyme in these cells.

Disease Relevance

The "CPT1A" form is associated with carnitine palmitoyltransferase I deficiency. This rare disorder confers risk for hepatic encephalopathy  hypoketotic hypoglycemia, seizures, and sudden unexpected death in infancy.  CPT1 is associated with type 2 diabetes and insulin resistance . Such diseases, along with many other health problems, cause free fatty acid (FFA) levels in humans to become elevated, fat to accumulate in skeletal muscle, and decreases the ability of muscles to oxidize fatty acids. CPT1 has been implicated in playing a critical role in these symptoms. The increased levels of malonyl-CoA caused by hyperglycemia and hyperinsulinemia inhibit CPT1, which causes a subsequent decrease in the transport of long chain fatty acids into muscle and heart mitochondria, decreasing fatty acid oxidation in such cells. The shunting of LCFAs away from mitochondria leads to the observed increase in FFA levels and the accumulation of fat in skeletal muscle.  Its importance in fatty acid metabolism makes CPT1 a potentially useful enzyme to focus on in the development of treatments of many other metabolic disorders as well.

lipoproteins

Despite the high heterogeneity found among
lipids, either in terms of their different classes
(fatty acids, triglycerides, cholesterol,
cholesterol esters and phospholipids), or even
within each of these classes, there is a feature
common to all of them - its high insolubility in
water. Indeed, although some of the lipids have
an amphipathic behavior (phospholipids and
cholesterol) they are predominantly apolar.
Since in our body it is necessary to transport
lipids from one organ to another, and the
solvent of all our fluids, including plasma, is
water, we have a potential problem... If the
lipids were able to circulate in their free forms
in the bloodstream, it would be the tendency of
the lipids to cluster in lipid droplets (such as
when olive oil is dropped in a glass of water),
which would, ultimately, lead to the occlusion of
blood vessels.
It is precisely to avoid this situation that the
plasma lipoproteins are synthesized. As the
name implies, the lipoproteins are
macromolecular complexes composed of lipids
and proteins and have the function of
transporting lipids (the only exception are fatty
acids! ) in the bloodstream, keeping them in a
partially soluble state. Basically, the idea is that
these are spherical structures with an extremely
hydrophobic interior (mostly composed of the
more nonpolar lipids - triglycerides and
phospholipids) and a polar surface to enable
interactions with water. Thus, in the surface
there are the polar groups of the phospholipids
and cholesterol. Therefore, by being able to
interact with water, lipoproteins can be in a
partially soluble state, preventing the formation
of hydrophobic lipid droplets that occur to
minimize the contacts of lipids with water.

Classes of lip protein

There are several classes of lipoproteins that
are grouped according to their density. Thus , in
order of increasing density, we have the
chylomicrons, VLDL, IDL (not a “true” class of
lipoproteins), LDL and HDL. Since the lipids are
less dense than water, the greater the fat
content of a lipoprotein, the less its density.
Regarding the size of the different lipoprotein
classes, this varies inversely with the density,
that is, the denser lipoproteins are the smaller ones.

Cholesterol metabolism

Introduction

Cholesterol is an extremely important biological
molecule that has roles in membrane structure as
well as being a precursor for the synthesis of the
steroid hormones and bile acids . Both dietary
cholesterol and that synthesized de novo are
transported through the circulation in lipoprotein
particles . The same is true of cholesteryl esters,
the form in which cholesterol is stored in cells.
The synthesis and utilization of cholesterol must be
tightly regulated in order to prevent over-
accumulation and abnormal deposition within the
body. Of particular importance clinically is the
abnormal deposition of cholesterol and cholesterol-
rich lipoproteins in the coronary arteries. Such
deposition, eventually leading to atherosclerosis, is
the leading contributory factor in diseases of the
coronary arteries.

Biosynthesis of cholesterol

Slightly less than half of the cholesterol in the body
derives from biosynthesis de novo . Biosynthesis in
the liver accounts for approximately 10%, and in the
intestines approximately 15%, of the amount
produced each day. Cholesterol synthesis occurs in
the cytoplasm and microsomes (ER) from the two-
carbon acetate group of acetyl-CoA.
The acetyl-CoA utilized for cholesterol biosynthesis
is derived from an oxidation reaction (e.g., fatty
acids or pyruvate) in the mitochondria and is
transported to the cytoplasm by the same process
as that described for fatty acid synthesis (see the
Figure below). Acetyl-CoA can also be synthesized
from cytosolic acetate derived from cytoplasmic
oxidation of ethanol which is initiated by
cytoplasmic alcohol dehydrogenase (ADH3). All the
reduction reactions of cholesterol biosynthesis use
NADPH as a cofactor. The isoprenoid intermediates
of cholesterol biosynthesis can be diverted to other
synthesis reactions, such as those for dolichol
(used in the synthesis of N -linked glycoproteins,
coenzyme Q (of the oxidative phosphorylation
pathway) or the side chain of heme- a. Additionally,
these intermediates are used in the lipid
modification of some proteins .

The process of cholesterol synthesis has five major
steps:
1. Acetyl-CoAs are converted to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)

2. HMG-CoA is converted to mevalonate

3. Mevalonate is converted to the isoprene based
molecule, isopentenyl pyrophosphate (IPP), with the concomitant loss of CO2

4. IPP is converted to squalene

5. Squalene is converted to cholesterol.

Pathway of cholesterol biosynthesis. Synthesis
begins with the transport of acetyl-CoA from the
mitochondrion to the cytosol. The rate limiting step
occurs at the 3-hydroxy-3-methylglutaryl-CoA
(HMG-CoA) reducatase, HMGR catalyzed step. The
phosphorylation reactions are required to solubilize
the isoprenoid intermediates in the pathway.
Intermediates in the pathway are used for the
synthesis of prenylated proteins, dolichol, coenzyme
Q and the side chain of heme a . The abbreviation
"PP" (e.g. isopentenyl-PP) stands for
pyrophosphate. Place mouse over intermediate
names to see structure.
Acetyl-CoA units are converted to mevalonate by a
series of reactions that begins with the formation of
HMG-CoA . Unlike the HMG-CoA formed during
ketone body synthesis in the mitochondria, this
form is synthesized in the cytoplasm. However, the
pathway and the necessary enzymes are similar to
those in the mitochondria. Two moles of acetyl-CoA
are condensed in a reversal of the thiolase reaction,
forming acetoacetyl-CoA. The cytoplasmic thiolase
enzyme involved in cholesterol biosynthesis is
acetoacetyl-CoA thiolase encoded by the ACAT2
gene. Although the bulk of acetoacetyl-CoA is
derived via this process, it is possible for some
acetoacetate, generated during ketogenesis, to
diffuse out of the mitochondria and be converted to
acetoacetyl-CoA in the cytosol via the action of
acetoacetyl-CoA synthetase (AACS). Acetoacetyl-
CoA and a third mole of acetyl-CoA are converted to
HMG-CoA by the action of HMG-CoA synthase.
HMG-CoA is converted to mevalonate by HMG-CoA
reductase, HMGR (this enzyme is bound in the
endoplasmic reticulum, ER). HMGR absolutely
requires NADPH as a cofactor and two moles of
NADPH are consumed during the conversion of
HMG-CoA to mevalonate. The reaction catalyzed by
HMGR is the rate limiting step of cholesterol
biosynthesis, and this enzyme is subject to
complex regulatory controls as discussed below.
Mevalonate is then activated by two successive
phosphorylations (catalyzed by mevalonate kinase,
and phosphomevalonate kinase), yielding 5-
pyrophosphomevalonate. In humans, mevalonate
kinase resides in the cytosol indicating that not all
the reactions of cholesterol synthesis are catalyzed
by membrane-associated enzymes as originally
described. After phosphorylation, an ATP-dependent
decarboxylation yields isopentenyl pyrophosphate,
IPP, an activated isoprenoid molecule. Isopentenyl
pyrophosphate is in equilibrium with its isomer,
dimethylallyl pyrophosphate, DMPP. One molecule
of IPP condenses with one molecule of DMPP to
generate geranyl pyrophosphate, GPP. GPP further
condenses with another IPP molecule to yield
farnesyl pyrophosphate, FPP. Finally, the NADPH-
requiring enzyme, squalene synthase catalyzes the
head-to-tail condensation of two molecules of FPP,
yielding squalene. Like HMGR, squalene synthase is
tightly associated with the ER. Squalene undergoes
a two step cyclization to yield lanosterol. The first
reaction is catalyzed by squalene monooxygenase.
This enzyme uses NADPH as a cofactor to
introduce molecular oxygen as an epoxide at the 2,3
position of squalene. Through a series of 19
additional reactions, lanosterol is converted to
cholesterol.
The terminal reaction in cholesterol biosynthesis is
catalyzed by the enzyme 7-dehydrocholesterol
reductase encoded by the DHCR7 gene. Functional
DHCR7 protein is a 55.5 kDa NADPH-requiring integral membrane protein localized to the microsomal membrane. Deficiency in DHCR7 (due to gene mutations) results in the disorder called Smith-Lemli-Opitz syndrome, SLOS . SLOS is characterized by increased levels of 7-dehydrocholesterol and reduced levels (15% to 27% of normal) of cholesterol resulting in multiple developmental malformations and behavioral problems.

Regulation of cholesterol synthesis

Normal healthy adults synthesize cholesterol at a
rate of approximately 1g/day and consume
approximately 0.3g/day. A relatively constant level
of cholesterol in the blood (150–200 mg/dL) is
maintained primarily by controlling the level of de
novo synthesis. The level of cholesterol synthesis is
regulated in part by the dietary intake of cholesterol.
Cholesterol from both diet and synthesis is utilized
in the formation of membranes and in the synthesis of the steroid hormones and bile acids . The greatest proportion of cholesterol is used in bile acid synthesis.

The cellular supply of cholesterol is maintained at a
steady level by three distinct mechanisms:

1. Regulation of HMGR activity and levels

2. Regulation of excess intracellular free cholesterol
through the activity of acyl-CoA:cholesterol
acyltransferase, ACAT

3. Regulation of plasma cholesterol levels via LDL receptor-mediated uptake and HDL-mediated reverse transport.

Regulation of HMGR activity is the primary means
for controlling the level of cholesterol biosynthesis.
The enzyme is controlled by four distinct
mechanisms: feed-back inhibition, control of gene
expression, rate of enzyme degradation and
phosphorylation-dephosphorylation.
The first three control mechanisms are exerted by
cholesterol itself. Cholesterol acts as a feed-back
inhibitor of pre-existing HMGR as well as inducing
rapid degradation of the enzyme. The latter is the
result of cholesterol-induced polyubiquitination of
HMGR and its degradation in the proteosome (see
proteolytic degradation below). This ability of
cholesterol is a consequence of the sterol sensing
domain, SSD of HMGR. In addition, when cholesterol
is in excess the amount of mRNA for HMGR is
reduced as a result of decreased expression of the
gene. The mechanism by which cholesterol (and
other sterols) affect the transcription of the HMGR
gene is described below under regulation of sterol
content .
Regulation of HMGR through covalent modification
occurs as a result of phosphorylation and
dephosphorylation. The enzyme is most active in its
unmodified form. Phosphorylation of the enzyme
decreases its activity. HMGR is phosphorylated by
AMP-activated protein kinase, AMPK (this is not the
same as cAMP-dependent protein kinase, PKA).
AMPK itself is activated via phosphorylation.
Phosphorylation of AMPK is catalyzed by at least 2
enzymes. The primary kinase sensitive to rising
AMP levels is LKB1. LKB1 was first identified as a
gene in humans carrying an autosomal dominant
mutation in Peutz-Jeghers syndrome, PJS. LKB1 is
also found mutated in lung adenocarcinomas. The
second AMPK phosphorylating enzyme is
calmodulin-dependent protein kinase kinase-beta
(CaMKKβ). CaMKKβ induces phosphorylation of
AMPK in response to increases in intracellular Ca2+
as a result of muscle contraction. Visit AMPK: The
Master Metabolic Regulator for more detailed
information on the role of AMPK in regulating
metabolism.
Regulation of HMGR by covalent modification. HMGR
is most active in the dephosphorylated state.
Phosphorylation is catalyzed by AMP-activated
protein kinase (AMPK) an enzyme whose activity is
also regulated by phosphorylation. Phosphorylation
of AMPK is catalyzed by at least 2 enzymes: LKB1
and CaMKKβ. Hormones such as glucagon and
epinephrine negatively affect cholesterol
biosynthesis by increasing the activity of the
inhibitor of phosphoprotein phosphatase inhibitor-1,
PPI-1. Conversely, insulin stimulates the removal of
phosphates and, thereby, activates HMGR activity.
Additional regulation of HMGR occurs through an
inhibition of its' activity as well as of its' synthesis
by elevation in intracellular cholesterol levels. This
latter phenomenon involves the transcription factor
SREBP described below.
The activity of HMGR is additionally controlled by
the cAMP signaling pathway. Increases in cAMP
lead to activation of cAMP-dependent protein
kinase, PKA. In the context of HMGR regulation, PKA
phosphorylates phosphoprotein phosphatase
inhibitor-1 (PPI-1) leading to an increase in its'
activity. PPI-1 can inhibit the activity of numerous
phosphatases including protein phosphatase 2C
(PP2C) and PP2A (also called HMGR phosphatase)
which remove phosphates from AMPK and HMGR,
respectively. This maintains AMPK in the
phosphorylated and active state, and HMGR in the
phosphorylated and inactive state. As the stimulus
leading to increased cAMP production is removed,
the level of phosphorylations decreases and that of
dephosphorylations increases. The net result is a
return to a higher level of HMGR activity.
Since the intracellular level of cAMP is regulated by
hormonal stimuli, regulation of cholesterol
biosynthesis is hormonally controlled. Insulin leads
to a decrease in cAMP, which in turn activates
cholesterol synthesis. Alternatively, glucagon and
epinephrine, which increase the level of cAMP,
inhibit cholesterol synthesis.
The ability of insulin to stimulate, and glucagon to
inhibit, HMGR activity is consistent with the effects
of these hormones on other metabolic pathways.
The basic function of these two hormones is to
control the availability and delivery of energy to all
cells of the body.
Long-term control of HMGR activity is exerted
primarily through control over the synthesis and
degradation of the enzyme. When levels of
cholesterol are high, the level of expression of the
HMGR gene is reduced. Conversely, reduced levels of cholesterol activate expression of the gene. Insulin also brings about long-term regulation of cholesterol metabolism by increasing the level of HMGR synthesis.

Digestion and absorption of lipid

Lipids are large molecules and generally are not
water-soluble. Like carbohydrates and protein,
lipids are broken into small components for
absorption. Since most of our digestive enzymes
are water-based, how does the body break down
fat and make it available for the various functions it
must perform in the human body?

From the mouth to the stomach

The first step in the digestion of triacylglycerols and
phospholipids begins in the mouth as lipids
encounter saliva. Next, the physical action of
chewing coupled with the action of emulsifiers
enables the digestive enzymes to do their tasks.
The enzyme lingual lipase , along with a small
amount of phospholipid as an emulsifier, initiates the
process of digestion. These actions cause the fats
to become more accessible to the digestive
enzymes. As a result, the fats become tiny droplets
and separate from the watery components.

In the stomach, gastric lipase starts to break down
triacylglycerols into diglycerides and fatty acids.
Within two to four hours after eating a meal, roughly
30 percent of the triacylglycerols are converted to
diglycerides and fatty acids. The stomach’s
churning and contractions help to disperse the fat
molecules, while the diglycerides derived in this
process act as further emulsifiers. However, even
amid all of this activity, very little fat digestion
occurs in the stomach.

As stomach contents enter the small intestine, the
digestive system sets out to manage a small hurdle,
namely, to combine the separated fats with its own
watery fluids. The solution to this hurdle is bile . Bile
contains bile salts, lecithin, and substances derived
from cholesterol so it acts as an emulsifier. It
attracts and holds on to fat while it is
simultaneously attracted to and held on to by water.
Emulsification increases the surface area of lipids
over a thousand-fold, making them more
accessible to the digestive enzymes.
Once the stomach contents have been emulsified,
fat-breaking enzymes work on the triacylglycerols
and diglycerides to sever fatty acids from their
glycerol foundations. As pancreatic lipase enters the
small intestine, it breaks down the fats into free
fatty acids and monoglycerides . Yet again, another
hurdle presents itself. How will the fats pass
through the watery layer of mucous that coats the
absorptive lining of the digestive tract? As before,
the answer is bile. Bile salts envelop the fatty acids
and monoglycerides to form micelles. Micelles have
a fatty acid core with a water-soluble exterior. This
allows efficient transportation to the intestinal
microvillus. Here, the fat components are released
and disseminated into the cells of the digestive tract
lining.
Just as lipids require special handling in the
digestive tract to move within a water-based
environment, they require similar handling to travel
in the bloodstream. Inside the intestinal cells, the
monoglycerides and fatty acids reassemble
themselves into triacylglycerols. Triacylglycerols,
cholesterol, and phospholipids form lipoproteins
when joined with a protein carrier. Lipoproteins
have an inner core that is primarily made up of
triacylglycerols and cholesterol esters (a
cholesterol ester is a cholesterol linked to a fatty
acid). The outer envelope is made of phospholipids
interspersed with proteins and cholesterol.
Together they form a chylomicron , which is a large
lipoprotein that now enters the lymphatic system
and will soon be released into the bloodstream via
the jugular vein in the neck. Chylomicrons transport
food fats perfectly through the body’s water-based
environment to specific destinations such as the
liver and other body tissues.
Cholesterols are poorly absorbed when compared
to phospholipids and triacylglycerols. Cholesterol
absorption is aided by an increase in dietary fat
components and is hindered by high fiber content.
This is the reason that a high intake of fiber is
recommended to decrease blood cholesterol. Foods
high in fiber such as fresh fruits, vegetables, and
oats can bind bile salts and cholesterol, preventing
their absorption and carrying them out of the colon.
If fats are not absorbed properly as is seen in some
medical conditions, a person’s stool will contain
high amounts of fat. If fat malabsorption persists the
condition is known as steatorrhea. Steatorrhea can
result from diseases that affect absorption, such as
Crohn’s disease and cystic fibrosis.

Storing and using of body fats
Before the prepackaged food industry, fitness
centers, and weight-loss programs, our ancestors
worked hard to even locate a meal. They made
plans, not for losing those last ten pounds to fit into
a bathing suit for vacation, but rather for finding
food. Today, this is why we can go long periods
without eating, whether we are sick with a vanished
appetite, our physical activity level has increased,
or there is simply no food available. Our bodies
reserve fuel for a rainy day.
One way the body stores fat was previously
touched upon in Chapter 4 "Carbohydrates" . The
body transforms carbohydrates into glycogen that
is in turn stored in the muscles for energy. When
the muscles reach their capacity for glycogen
storage, the excess is returned to the liver, where it
is converted into triacylglycerols and then stored as
fat.
In a similar manner, much of the triacylglycerols the
body receives from food is transported to fat
storehouses within the body if not used for
producing energy. The chylomicrons are
responsible for shuttling the triacylglycerols to
various locations such as the muscles, breasts,
external layers under the skin, and internal fat
layers of the abdomen, thighs, and buttocks where
they are stored by the body in adipose tissue for
future use. How is this accomplished? Recall that
chylomicrons are large lipoproteins that contain a
triacylglycerol and fatty-acid core. Capillary walls
contain an enzyme called lipoprotein-lipase that
dismantles the triacylglycerols in the lipoproteins
into fatty acids and glycerol, thus enabling these to
enter into the adipose cells. Once inside the adipose
cells, the fatty acids and glycerol are reassembled
into triacylglycerols and stored for later use.
Muscle cells may also take up the fatty acids and
use them for muscular work and generating energy.
When a person’s energy requirements exceed the
amount of available fuel presented from a recent
meal or extended physical activity has exhausted
glycogen energy reserves, fat reserves are
retrieved for energy utilization.
As the body calls for additional energy, the adipose
tissue responds by dismantling its triacylglycerols
and dispensing glycerol and fatty acids directly into
the blood. Upon receipt of these substances the
energy-hungry cells break them down further into
tiny fragments. These fragments go through a
series of chemical reactions that yield energy,
carbon dioxide, and water.

Pros and Cons of genetic Engineering

The science of indirect manipulation of the genes of
an organism by using some techniques such as
molecular cloning & transformation to change the
structure & nature of the genes is referred to as
genetic engineering. This process can show up
significant transformation in an organism’s
characteristics through DNA manipulation which
can be the same with the code inscribed on each
cell determining the way it functions. Genetic
engineering has benefits and disadvantages just
like the other science.

The 4 Pros of Genetic Engineering

1. Better Flavor, Growth Rate and Nutrition

Crops like potato, soybean and tomato are now
genetically engineered in order to get the new
strains with improved nutritional qualities as well as
to increase yield. Crops that are genetically
engineered are expected to possess the capability
to grow on a land that is recently not ideal for
cultivation. The genes manipulation in crops will
improve the nutritional value as well as the growth
rate of these crops.

2. Pest-resistant Crops and Extended Shelf Life

Engineered seeds can resist pests and they can
survive from harsh weather conditions.
Biotechnology could be used in making the food
spoilage process slow down. It can result to fruits
or veggies with greater and better shelf life.

3. Genetic Alteration to Supply New Foods

Genetic engineering can also be used in producing
completely new substances like proteins or other
nutrients on food. It can be used in increasing their
medicinal worth

4. Modification of the Human DNA

When the genes are responsible for some
exceptional qualities among individuals could be
exposed, these genes could be synthetically
introduced into the genotypes of another individual.
Genetic engineering among humans can be also
used in changing the human DNA to show desirable
structural as well as functional modifications in
them

The 4 Cons of Genetic Engineering

The following are the issues that genetic
engineering can trigger:

1. May Hamper Nutritional Value

Genetic engineering on food also includes the
infectivity of genes in root crops. These crops might
supersede the natural weeds. These can be
dangerous for the natural plants. Unpleasant
genetic mutations could result to allergies among
crops. Some people believe that this science on
foods can hamper the nutrients contained by the
crops although their look and taste were enhanced.

2. May Introduce Risky Pathogens

Horizontal gene shift could give increase to other
pathogens. While it increases the immunity against
diseases among the plants, the resistant genes can
be transmitted to harmful pathogens.

3. May Result to Genetic Problems

Gene therapy on humans can end to some side
effects. While relieving one problem, the treatment
may cause the onset of another issue. As a single
cell is liable for various characteristics, the cell
isolation process will be responsible for one trait
will be complicated.

4. Unfavorable to Genetic Diversity

Genetic engineering can affect the diversity among
the individuals. Cloning might be unfavorable to
individualism. Furthermore, such process might not
be affordable for poor. Hence, it makes the gene
therapy impossible for an average person.

FATE OF A PYRUVATE

Well, the fate of pyruvate depend on two factor
whether oxygen is present or not.
In the presence of oxygen (aerobic condition)
pyruvate is converted to acetyl-CoA by the enzyme
pyruvate dehydrogenase which enters the TCA or
Kerb cycle where large (most) of ATP molecules is
generated.