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Lecture 1

BCHM 316 Lecture Notes - Lecture 1: Pentose Phosphate Pathway, Pyruvate Carboxylase, Glycogen Phosphorylase


Department
Biochemistry
Course Code
BCHM 316
Professor
Glenville Jones
Lecture
1

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LECTURE 1 OVERVIEW
The fundamentals of metabolism
o Metabolism = catabolism + anabolism
Catabolism = breaking down of food material into smaller particles
Uses stored nutrients, ingested foods, solar photons
Takes energy containing nutrients (carbohydrates, fats,
proteins), makes ATP, then produces energy-depleted products
such as CO2, H20, NH3
Anabolism = synthesis of macromolecules from small particles
Makes osmotic work, mechanical work, complex biomolecules,
other cellular work
Takes precursor molecules (amino acids, sugars, fatty acids,
nitrogenous bases) and uses ATP to make macromolecules
(proteins, polysaccharides, lipids, nucleic acids)
Important features of metabolic pathways
o Efficiency
Energy cell level ATP, NADH, FADH2
o ATP is the universal currency (NADH is almost as good)
o NADH+FADH2 can be converted to ATP, but also act as
reducing agents
o NADPH is used in anabolism
o FADH2 can act as a sink/storage of energy
Energy tissue level glucose, fatty acids, ketone bodies
Building blocks amino acids, isoprenoids, fatty acids, DNA
bases
ATP
Derivative of adenosine, 3 phosphate groups
ATP = usually refers to the terminal (high-energy) 2 bonds (the
α-β ad β-γ
At high concentrations ATP acts as its own inhibitor
o Neurons use PCr since it is a fast source of energy
o Versatility
Versatile : can use carbohydrate, prtein, fat, etc.
Body can easily convert proteins <-> sugar <-> fatty acid with
exceptions of essential aa and fa
Adaptable when supply problems- fuel stores & starvation
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o Specialization
Multiple pathways with different roles
Glycolysis -> energy production
Gluconeogenesis -> glucose resynthesis
Citric acid cycle -> building block and energy
Pentose phosphate pathway -> NADPH and pentose synthesis
Glycogen synthesis -> storage of energy (short term)
Glycogen breakdown -> mobilisation of energy
Fatt aid β-oxidation -> energy production
Fatty acid biosynthesis -> phospholipid and triglyceride synthesis
Triglyceride biosynthesis -> storage of energy (long term)
Triglyceride mobilisation -> mobilisation of energy
Ketogenesis -> emergency source of energy for tissues
Organ specialization : liver vs brain
Tissue specialisation (not every tissue can do the same things)
Glycogenolysis (muscle, liver)
Gluconeogenesis (kidney, liver)
Triglyceride synthesis, fatty acid mobilization (adipose tissue &
liver)
Ketogenesis (liver)
o Liver does everything
If ou hae pole ith ou lie, ou’e
screwed
In a starvation state -> each tissue acts selfishly to take other
alternatives from altruistic liver
o Liver can make fatty acid -> acetyl CoA as energy for it to
use itself
Insulin Receptor
o Metabolic effect
Glucose uptake (muscle,adipose), synthesis(liver
and muscle) and glycolysis Iliver and muscle)
Target enzymes (GLUT4, glycogen synthase, PFK-1)
o Regulation
Complex regulation :cell level vs intercellular (hormones)
Enzyme activity changes = short term (mins/hours)
o Eg Citrate on Acetyl CoA-Carboxylase
Enzyme amounts = Long-term (hours/days)
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o Low fat diets & hormonal changes on acetyl CoaA-
carboxylase and other F.A. synthetic enzymes
Integration of metabolism
Gluose seso i paeati β
Why so many pathways to understand
What are the advantages of using a single energy currency?
o Cellular enzymes that require energy input can use a commonly available
energy source. The cell has only one major energy source to maintain at an
appropriate concentration. Notice that the cell maintains a high ATP
concentration religiously.
Why do cells like myocytes and neurons use phosphocreatine as well as ATP for
energy?
o ATP generation and regeneration will just not work quickly enough for all
energy applications. Those requiring FAST regeneration of energy such as
fast-tith usle otatio o ee tasissio eed a eeg
uffe ad thus a faste a of egeeating ATP and this is from another
high energy form: phosphocreatine. The enzyme : Creatine kinase uses
phosphocreatine (10-20mM) to regenerate ATP rapidly
If enzymatic steps are reversible: why use two pathways to synthesize and
breakdown common cellular components?
o Regulation. By having separate enzymes we can regulate the two
processes independently of one another. If we carry out two reciprocal
pathways = (eg glycolysis and gluconeogenesis) simultaneously, this is
alled futile lig. “uh futile ycles can generate heat and also have
advantages such as keeping both pathway enzymes primed and ready to
go when needed (like idling your stationary car)
LECTURE 2 CARBOHYDRATE STRUCTURE
Review carbohydrate structure
o Mammals use D-isomers of sugars
Determine chirality by comparing hydroxyl to position of reference
ao if it’s o the ight it’s D
Remind you of carbohydrate nomenclature
Carbohydrate polymers in biochemistry
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