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OUTLINE
I. Metabolism Catabolic Processes
A. Categories of Metabolism
Aerobic: Glucose pyruvate acetyl CoA
II. Intermediary Metabolism
Glycolysis
A. Energy Metabolism
Anaerobic: Glucose Lactate
III. Metabolic Pathways
Fatty acids Acetyl CoA
IV. Metabolic Fuels
+
β – oxidation NADH-H and FADH
2
A. Fates of Glucose
(For chemiosmotic production of ATP)
B. Fates of Lipids
+
C. Fates of Amino Acids Acetyl CoA oxidation NADH-H and FADH2
Citric Acid Cycle (For chemiosmotic production of ATP)
V. Intracellular Location of Basic Pathways
VI. Metabolic Regulation
All 3 food groups converge here
A. Patterns of Metabolic Regulation
Electron Electrons passed down to O
2
VII. Clinical Correlation
Transport
Chemiosmotic coupling
VIII. Appendix System
IX. Competencies
Nitrogen:
AA Catabolism -Redistributed if reduced
-Eliminated by urea cycle if excess
OBJECTIVES
Table 1. Catabolic Processes and their Products
General Objective:
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[BIOCHEMISTRY] 21- Go K, Golingan, Gomez, Gonzales A, Gonzales S, Gorospe, Hamtig,
Hechanova
[BIOCHEMISTRY] 2.1 Introduction to Metabolism – Dr. Balcueva
- Most organisms derive both the raw materials and the - Requirement for metabolic
fuel is relatively constant
energy for biosynthesis from organic fuel molecules such as throughout the day
(physical activity increases metabolic rate
glucose only by 40-50% over metabolic rate)
- Need to form reserves of glycogen and triacylglycerol for use
III. METABOLIC PATHWAYS during intervening time when there is no intake of food
- Obesity: Intake of metabolic fuels is consistently greater
- Sequences of reactions that include the reactants,
intermediates, products and the enzymes involved than energy expenditure; surplus
is stored largely as
triacylglycerol in the adipose tissue
- 3 molecules catabolized to produce energy:
- Emaciation: Intake of metabolic fuels is consistently lower
Carbohydrates
than energy expenditure, there are negligible reserves of fat
Protein
and carbohydrate; amino acids from protein turnover are
Fats
used for energy-yielding metabolism rather than replacement
- Products of digestion:
protein synthesis
Glucose
Amino acids
IV. METABOLIC FUELS
Fatty acids and glycerol
- In different phases/ levels of glucose in the body:
- All the products of digestion are metabolized to a common
Fed state – metabolic fuel is glucose
product: acetyl-CoA
Fasting state – glycogen, fatty acids, amino acids,
Acetyl-CoA is oxidized by the citric acid cycle (CAC)
ketone bodies
CAC substrate
- Major hormones that control utilization of fuel: Insulin and
- Carbohydrates simple sugars (glucose) Acetyl-CoA
Glucagon
- Protein Amino acids (composed of carbon skeleton and
Insulin
amino group) Acetyl-CoA
o In both liver and skeletal muscle, insulin acts to
- Fat Fatty acids + glycerol Acetyl-CoA
stimulate glycogen synthetase and inhibit glycogen
phosphorylase
o In adipose tissue, insulin stimulates glucose uptake,
its conversion to fatty acids, and esterification to
TAG. Extracellular lipoprotein lipase is synthesized
and activated in response to insulin.
Glucagon
o Inhibits glycogen synthetase and activates glycogen
phosphorylase in the liver.
o In adipose tissue, increased glucagon results in
inhibition of lipogenesis.
Fates of Glucose
1. Converted to pyruvate acetyl CoA + CO + H O
2 2
Glycolysis
- Can occur anaerobically (oxygen absent) but instead of
pyruvate, the product will be lactate
Figure 1. Overview of the metabolic pathways
- Linked to oxidative phosphorylation and thus, also
producing ATP
- Amino acids are not stored in the body
Pentose Phosphate Pathway
Excess/not needed amino group is degraded and
- A source of reducing equivalents but instead NADPH is
excreted as urea; carbon skeleton catabolized to acetyl-
used for biosynthesis
CoA and converted to fats or glucose
- Source of ribose for nucleotide and nucleic acid synthesis
- Glucose stored as glycogen in the liver and muscles
- In liver and skeletal muscles: reduction of glutathione
- Triacylglycerol stored in the adipose tissue
Acyl glycerol (fat) Pathway
- Citric Acid Cycle: Acetyl CoA is oxidized so energy is
- Triose phosphate glycerol moiety of triacylglycerols
released as reducing equivalent (2H) which is captured by
Amino Acid Synthesis
acceptors (ex. NADP, NAD, ADP, FMN, etc.)
- Via pyruvate and/or via intermediates of TCA
Energy released: not wasted, but stored; can be brought
Steroid Synthesis
to mitochondria to be converted to ATP (in electron
- Acetyl-CoA is a precursor of fatty acids and cholesterol
transport chain)
Glycogenesis
Releases CO2 as well
- Formation of glycogen when glucose in in excess
Gluconeogenesis
Metabolic process:
- Synthesis of glucose from non-carbohydrate sources such
- Nature of diet sets the basic pattern of metabolism
as lactate, amino acids, glycerol
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[BIOCHEMISTRY] 21- Go K, Golingan, Gomez, Gonzales A, Gonzales S, Gorospe, Hamtig,
Hechanova
[BIOCHEMISTRY] 2.1 Introduction to Metabolism – Dr. Balcueva
Dietary Lipids:
Hydrolyzed to monoacylglycerols and fatty acids
Re-esterified in intestinal mucosa and packaged with protein
Lymphatic system as chylomicrons
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[BIOCHEMISTRY] 21- Go K, Golingan, Gomez, Gonzales A, Gonzales S, Gorospe, Hamtig,
Hechanova
[BIOCHEMISTRY] 2.1 Introduction to Metabolism – Dr. Balcueva
Fed 40 Hours 7 Days
Skeletal muscles: It utilizes glucose as its energy
Fasting starvation
source, resulting to lactate and CO2 formation. It stores
Glucose 5.5 3.6 3.5
glycogen for muscle contraction and represents a
Free fatty 0.30 1.15 1.19
considerable amount ofprotein, reserved for use during
acids
starvation.
Ketone Negligible 2.9 4.5
Adipose tissue: It is considered the main fuel reserve
bodies
of the body, used during starvation. Glucagon activates
Table 4. Plasma Concentrations of Metabolic Fuels (mmol/L) in the Fed
a hormone-sensitive lipase, which hydrolyzes
and Fasting States (The amount of Ketone bodies (negligible in Fed
State) and Free fatty acids increase as one approaches the starvation
triacylglycerols yielding glycerol and fatty acids. These
state. The opposite is true for Glucose)
are then released into the bloodstream as lipoproteins.
(Source:
VI. METABOLIC REGULATION
http://www.biochem.ucl.ac.uk/~dab/MSc%20clinbioc/MSc%20gluc
- Most pathways are irreversible under physiologic conditions
ose%20homeostasis.pdf)
- When a metabolite enters the pathway, each step occurs in
Phosphorylation:
Major metabolic features of principal organs
o activates enzymes regulating catabolic
For the summary of the major metabolic features of the principal
pathways
organs, see appendix
o inhibits enzymes regulating anabolic pathways
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[BIOCHEMISTRY] 21- Go K, Golingan, Gomez, Gonzales A, Gonzales S, Gorospe, Hamtig,
Hechanova
[BIOCHEMISTRY] 2.1 Introduction to Metabolism – Dr. Balcueva
3. Supply of Substrate o ↑ rate of protein synthesis in response to ↑availability
of
amino acids and metabolic acids is a response also to
ATP or ADP
4. Hormones insulin action
COMPETENCIES
- Given a normal person, identify biochemical pathways or processes of
carbohydrates that are involved to achieve normal growth and
development.
- Apply the biochemical concepts and principles that will help explain the growth
and development of the normal person
- Correlate the biochemical or molecular basis with the growth and development of
the normal person
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[BIOCHEMISTRY] 21- Go K, Golingan, Gomez, Gonzales A, Gonzales S, Gorospe, Hamtig,
Hechanova