ANABOLISM NOTE: Although the reaction is reversible the hydrolysis
of the pyrophosphate pushes it to the right
- Anabolism happens if there is an abundance of
food intake, ATP calories, or energy, so,
therefore, the body must able stored those
excess fuels (a form of glycogen and fat)
RECALL: We can’t store protein as protein. The way we
stored carbohydrates as glycogen and fat as
triglycerides. More storage in fat compared to glycogen
but the first pun-on is the glycogen storage (~500
grams), parehas rana sa kung mag breakdown ta mas
unahon ang glycogen dayun ang fats.
- Anabolism is required energy input, so ATP
broken down and form in ADP and Pi so that the
energy is would be released and be captured for
anabolism
- To build a larger molecule, we need oxygen
from the breakdown of ATP
ANABOLISM OF CARBOHYDRATES
GLYCOGENESIS
The Synthesis of Glycogen
Is An Energy Consuming Pathway
- Reductive
● Glycogen is synthesized via uridine diphosphate
glucose (UDP – glucose).
- Glycogen is composed of many glucose
units
- Individual glucose is combined of UDP -
glucose
● Synthesis: Glycogen(n) + UDP-glucose →
glycogen(n+1) + UDP
- To activate the glucose for glycogen
synthesis so need dapat ma attached
ang glucose with UDP.
● Degradation: glucogen(n) + Pi → Glycogen(n-1)
+ glucose 1-phosphate.
- This is done in the liver and muscle
NOTE: Glycogen synthesis and degradation utilize
separate pathways.
NOTE: The main enzyme is the glycogen synthase - this
enzyme to regulate, gina manipulate para ma regulate
nato ang rate sa glycogenesis
Luis Leloir Nobel Prize in Chemistry, 1970
- for his discovery of sugar nucleotides and their
role in the biosynthesis of carbohydrates
UDP glucose is the activated form of glucose.
UDP-glucose pyrophosphorylase
UTP - is derived from the ATP. The Adenosine from the
ATP is just changed to uridine.
The glucose is activated due to the input of ATP, formed
of UTP.
Glycogen synthase catalyzes α-1,4 linkages
The combining of UDP-glucose together is formed α
(glucosyl units) 1,4 linkages
- Glucosyl units a polymer of UDP-glucose
combined together via 1,4 glycosidic bond, the
main enzyme - glycogen synthase
Glycogen synthase (linear ang ginahimo na structure sa
glycogen) ang naga add og UDP-glucose (one at a time)
until mahimo na siya og taas na chain. So the glycogen
synthase ang naga work ana. Before mag catalyze si
glycogen synthase need og primer. Primer ang pinakuna
ma produced before si glycogen synthase. A primer of at
least 4 units is required via glycogenin.
Branching enzyme forms α-1,6 linkages:
Remodeling
Branching enzyme is the enzyme responsible for the
branching structure of glycogen. If wala ang branching
enzymes the normal glycogen can't be produced and
pag wala ing-ana sa tao there are many consequences
ana sa body sa tao (e.g. development of plaque). The
purpose of branching of glycogen for more soluble if
linear lang dili siya soluble sa water and it can form
plaques in the liver and worst in the heart leading to
many consequences or early death.
The enzyme breaks the α-1,4 link and forms a α-1,6 link.
A large number of terminal residues are now available
for glycogen phosphorylase; degradation.
Branching increases the solubility of glycogen.
AND THIS POINT NAKA FORM KAG GLYCOGEN.
When blood glucose levels are high, insulin (anabolic)
activates protein phosphatase 1 which stimulates
glycogen synthesis.
Explanation: The insulin is to upregulate or increase
glycogenesis. This usually happens after eating or
postprandial (after meal) kay motaas man atong blood
glucose level so that time the pancreas that stimulates to
release insulin so that the blood glucose levels should
be lower for the cells to take out and then pwede nata
makaproduce of glycogen out of the glucose that we
absorb and most especially daghan og glucose so dapat
ma activate si glycogenesis. Again, insulin is the
promoter of glycogenesis.
- This is accomplished through a complex highly
regulated signal transduction pathway.
Remember: Glycogen metabolism in the liver regulates
blood glucose levels.
Blood glucose levels rise after ingestion of Lipogenesis uses a ​multi-enzyme complex called fatty
carbohydrates, leading to glycogen synthesis. acid synthase​.
Fatty acid ​degradation uses individual enzymes​, not
necessarily physically associated.

Lipogenesis intermediates are ​carried by

ACP (acyl carrier protein)​ - activated form of fatty acid
CoA is the carrier for intermediates​ formed in the fatty
acid spiral

NOTE: The counterpart of the Fatty Acid synthesis is the

Beta-oxidation. Fatty Acid synthesis is the reverse of
beta-oxidation.
Phosphorylase is the enzyme responsible for
Glycogenolysis/breaks down glycogen
The essential chemistry of the two processes are
basically reversals of each other​. Both oxidation and
When glucose is added, glycogen synthase is activated.
synthesis of fats ​use activated 2 C intermediate:
It happens after meals. As a consequence, due to
acetyl-CoA​. Acetyl-CoA in fat synthesis is temporarily
increased insulin, the glucagon can be low and also the
bound to an enzyme complex as malonyl-CoA. The
activity of the phosphorylase would be lower (Liver).
synthesis of ​malonyl-CoA is the 1st step​ of fatty acid
Glycogenesis and Glycogenolysis are antagonistic.
synthesis
Inactivation of phosphorylase and an activation of
glycogen synthase.

Glucagon = starved state; stimulates glycogen

breakdown, inhibits glycogen synthesis.

High blood glucose levels = fed state; insulin stimulates

glycogen synthesis and inhibits glycogen breakdown.
- Glucagon decreases and insulin is increased.

Acetyl-CoA delivered from the mitochondrial matrix to

ANABOLISM OF FATS
Kung mapuno na ang storage for glycogen and the
excess og glucose, amino acids and beyond the trace
holes now will be diverted to production of fats.
Synthesis of Triglycerides
The ​major building block​ for the synthesis of
triacylglycerols, in tissues other than adipose tissue, is
glycerol-3-phosphate​.
the cytosol by the citrate-malate-pyruvate shuttle.
WHY CYTOPLASM NEEDS THE FATTY ACID
SYNTHESIS?
Para dili ma confuse ang cells.
Provides Acetyl CoA to cytosol for biosynthesis of fatty
acids

WHAT ABOUT ADIPOSE TISSUE?
Adipocytes lack ​glycerol kinase​, therefore, the 3C
dihydroxyacetone phosphate​, produced during
glycolysis​, is the precursor for triacylglycerol synthesis in
adipose tissue.
In order to make Palmitic Acid, for example, steps in
fatty acid synthesis may occur 7 times, like the
beta-oxidation.

This means that adipocytes must have ​glucose to

oxidize​ in order to store fatty acids in the form of
triacylglycerols.

There are two anabolic pathways of this:

1. Fatty Acid synthesis (Fatty Acid)
2. Lipogenesis/Triglyceride synthesis (Fatty Acid +
Glycerol)
occurs primarily in the cytoplasm of these tissues:
- Liver
- Adipose (fat)
- Central Nervous System - neurons A. CONDENSATION:
- Lactating mammary gland The activated of the Acetyl-CoA, acetyl ACP (2),
REMEMBER: Glucagon and epinephrine inhibit fatty is combined in Malonyl-ACP (2C) to form
acid synthesis, and insulin stimulates it. acetoacetyl ACP.

Also, insulin (anabolic) stimulates the Fatty acid In the first cycle of the fatty acid biosynthetic
synthesis and Lipogenesis. The breakdown of fats, pathway, acetyl ACP is converted to butyryl
Lipolysis and Beta-oxidation, stimulates of those are ACP.
glucagon and epinephrine (catabolic).
B. HYDROGENATION (energy input - endergonic)
Acetoacetyl ACP is converted to
Fatty Acid Synthesis and Oxidation Compared: Beta-Hydroxybutyryl ACP. This is the step
Pathway for fatty acid synthesis is in ​cytoplasm​. where NADPH is oxidized to form NADP.
FA oxidation occurs in ​mitochondria​.
C. DEHYDRATION
Lipogenesis involves ​oxidation of NADPH​. Beta-Hydroxybutyryl ACP is converted to
F.A. spiral involves ​reduction of FADH+ & NAD+​. Crotonyl ACP. Water removed.

D. HYDROGENATION
Crotonyl ACP is now converted to Butyryl ACP.
Another NADPH is oxidized to form NADP.
The sequence of cycles needed to produce a C16 fatty
acid from acetyl ACP.
If we have palmytic acid, it has occurred 7 times/rounds.
We have 14 NADPH molecules that are oxidized to form
NADP.
Each loop represents one cycle.
The acyl group is now ready to condense with a new
malonyl group to repeat the process. When fatty acyl
group becomes 16 carbons long, a thioesterase
hydrolyzes it, forming free palmitate:
When glycerol is added, this process is called
lipogenesis.
Palmitate is then released from the enzyme by a
thioesterase reaction and can then undergo separate
elongation and/or unsaturation to yield other fatty acid
molecules.
Therefore the process of oxidation is reversely in the
process of the Fatty acid synthases.
Cholesterol synthesis:
• Cholesterol used in every cell membrane
• Precursor for:
- Bile salts
- Vitamin D
- Adrenal hormones:
Glucocorticoids: cortisol
Mineralocorticoids: aldosterone
- Sex hormones:
Estrogens (female)
Progestins (pregnancy)
Androgens (male): one androgens is
Testosterone
The hormones that have cholesterol as a precursor that
is called steroid hormones.
• Cholesterol has 27 carbons
• Synthesis takes 15 Acetyl CoA molecules
• 27 separate enzymatic steps
• Occurs in the ​liver​, makes 1.5 to 2.0 g/day
• Average diet takes in 0.3 g cholesterol/day
Biosynthesis of cholesterol begins with 3 acetyl CoA
molecules forming a 6 C mevalonate molecule.
HMG-CoA to Mevalonate by the HMG-CoA reductase -
lowering the drugs called ​statins​.
Statins inhibit the HMG-CoA reductase so that the
mevalonate is not produced. May also help with
osteoporosis and as anti inflammatory for virus that
affects heart
Relationship between
Lipid and Carbohydrate Metabolism
Acetyl CoA is the link between lipid and carbohydrate
metabolic pathways.
Glucose by pyruvate, Glycerol by DHAP via glycolysis, &
Fatty acids (beta-oxidation) all degrade into acetyl CoA
Biosynthesis (anabolism) of fatty acids, ketone bodies, &
cholesterol all use acetyl CoA except the glycogenesis.
NOTE: So that the Acetyl-CoA is a central metabolite
and also the amino acids that formed ketogenic amino
acids.
Glucose, Glycerol, & Fatty acids all supply acetyl CoA to
be oxidized in the Krebs cycle.
Ketone bodies form when there is an imbalance between
lipids and carbohydrates: Inadequate amounts of
glucose, during adequate times of lipid metabolism.
Cholesterol and Fatty Acid synthesis occurs when the
body is overly rich in acetyl CoA, beyond energy needs
for cellular activity.
Review: can you…
• Describe ATP production from F.A. Oxidation
• Define “Ketone Bodies” & explain formation
significance
Ketone bodies: Chemicals that the body makes
when there is not enough insulin in the blood
and it must break down fat instead of the sugar
glucose for energy. The ketone bodies -
acetone, acetoacetate, and
beta-hydroxybutyrate - are toxic acidic
chemicals. Ketone bodies have an important
role as an energy source during starvation. In
the liver, fatty acyl CoA is converted into ketone
bodies (3-hydroxybutyrate [βOHB] and
acetoacetate [AcAc]). The ketone bodies are
efficiently metabolized in peripheral tissues
except in the brain
• Compare & contrast Lipogenesis to biosynthesis of
Cholesterol • Compare & contrast relationship between
Lipid & Carbohydrate Metabolism • Discuss effect of
exercise on carbohydrate & lipid metabolism • Discuss
cholesterol lowering drugs
For your own reading lang ning review...
PENTOSE PHOSPHATE PATHWAY
(HMS - hexose monophosphate shunt )
REMEMBER: Glucose-6-phosphate many uses.
The pentose pathway is a shunt (diversion).
• The pathway begins with the glycolytic intermediate
glucose 6-P.
• It reconnects with glycolysis because two of the end
products of the pentose pathway are glyceraldehyde 3-P
and fructose 6-P; two intermediates further down in the
glycolytic pathway.
• It is for this reason that the pentose pathway is often
referred to as a shunt.
When glucose is very abundant, the shunt can be
performed in the form of PPP and also Glycolysis can be
performed.
When moderate glucose only glycolysis occurs.
 NADPH + H+ is formed from two separate reactions.

The glucose 6-phosphate DH (G6PD) reaction is the rate

limiting step and is essentially irreversible.

Cells have a greater need for NADPH than ribose

5-phosphate.

The first intermediate in PPP is G6P. G6P is diverted

when the glucose is excess. It is shunted because later
on we can produce Glyceraldehyde 3-phosphate and
also Fructose 6-phosphate.

WHAT DOES THE PENTOSE PHOSPHATE PATHWAY

ACHIEVE?
• The pathway yields reducing potential in the form of
NADPH to be used in anabolic reactions requiring
electrons.
• Provides glycolytic intermediates
• The pathway yields ribose 5-phosphate. – Nucleotide
biosynthesis leading to:
•DNA
•RNA

YAMA! MAG CASE STUDY NA SAD DAW ABOUT SA

G6P DEFICIENCY!

For antioxidant systems. Remember ang naga generate 1ST PHASE:

sa tanan ani nga system kay mga antioxidants. So after
glutathione ma-oxidized then glutathione reduced form
so kailangan ani kay NADPH. NADPH reduces all those
radicals.

It is called oxidative stage kay tanan intermediates kay gi

oxidized to in order to form NADPH (step 1 and 3) then
makaproduced og Ribulose-5-phosphate then go to 2nd
phase.
NGANO ACTIVE ANG PPE SA MGA TISSUES (nga
naa sa table)?
Since the product of PPE is NADPH and this NADPH is
The nonoxidative phase of the
required some synthesis and detoxification (naa sa table
pentose pathway
1)
The extensive carbon atom rearrangement. 10 carbon
ang all the gi rearranged lang siya pag abot diri nga
NADPH is a phosphorylated form of NADH (add lang
phase. Then kung icombine si Xylulose og Ribose
kag phosphate)
makaproduced kag Sedoheptulose and Glyceraldehyde
by the enzyme of transketolase.
In general, with some exceptions, NADH is used to drive
the phosphorylation of ADP to ATP. NADPH is used
where reducing potential is required for synthetic
reactions or anabolic reaction.

The pentose pathway can be divided into two phases:

1. Oxidative - where the NADPH is produced
2. Nonoxidative - where the sugar is produced;
where ribulose biphosphate is produced; where
glycolytic intermediates (F6P and G3P) are
produced. • Transketolase (TPP) and transaldolase are the link
- Non-oxidative interconversion of sugars back to glycolysis.
• Glyceraldehyde 3-phosphate
• Fructose 6-phosphate
• Net result: 3C5 ↔ 2C6 + C

Epimerase: inter-converts stereoisomers ribulose-5-P

and xylulose-5-P.

Isomerase: converts the ketose ribulose-5-P to the

aldose ribose-5-P.

⬥ ​Transketolase​ transfers a 2-C fragment from

xylulose-5-P to either ribose-5-P or erythrose-4-P.
⬥ ​Transketolase utilizes as prosthetic group thiamine
pyrophosphate (TPP)​, a derivative of vitamin B1 .
Pyruvate Dehydrogenase of Krebs Cycle also utilizes
TPP as prosthetic group.