Unit 2: Biochemistry

Unit Topics:
pH, Metabolic reactions, Fuels,
Wastes, & Physiological States
Assigned Unit Homework
• Do assignments embedded within unit PPT.

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“Physiological pH”

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 Important:

“Physiological pH” range is narrow:

just 7.4 ± 0.05.

“The body is an acid factory” that produces

excess free H+,
which drives down pH.

Expect redundant N.F.C. mechanisms to

“buffer” (neutralize) acid.
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Glucose + O2 → CO2 + H2O + ATP
(C6H12O6)

Seems harmless but spontaneous dissociation

lowers pH: CO2 + H2O → H2CO3 = “carbonic acid”

(“Acids” are molecules “with a free H+ to give”)

H+ + HCO3-
Carbonic acid
Bicarbonate ion

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Amino acid (AA)

Hydrochloric
acid (HCl)

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 Excess free H+ is neutralized
using buffer molecules
• Anions make good buffers, and there are lots of them
around (redundancy principle at work).
• Buffers “sponge up” H + when pH falls –AND- “free up” H+
when pH rises.
• Bicarbonate ion
• Phosphate ion
• = same Pi that comes off ATP
• Proteins at physiological pH ~7.4 are anionic
• e.g. blood albumin made by liver
• Start a liver list! Add “Blood pH control via albumin
synthesis” to it.

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 Exhale CO2+H2O = “Bye,
bye, carbonic acid!”

Excess free H+

Urine tends to be low pH 7

“Postprandial alkaline tide”
 SOME cell types make H2CO3 on purpose & fast,
using the enzyme Carbonic Anhydrase
• CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
• Law of Mass Action: Excess CO2 pushes rxn RIGHT; insufficient
CO2 pushes it LEFT.
• C.A. speeds up the reaction in either direction, either MAKING
free H+ or BINDING free H+ into harmless H2O.
• Looking ahead, from 211:
– What organ makes an acid-enriched fluid as its job?
– What organs make bicarbonate-enriched fluids as their job?
• Homework: learn to draw this reversible reaction quickly and
to put the C.A. enzyme in the right spot (↔). Make sure you
understand the Law of Mass Action which encourages the
direction in which ANY chemical reaction proceeds.

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 Acidosis: when body pH falls too low.
Alkalosis: when body pH rises too high.

pH RoT violations can be a result of

MANY things (go look at slide 7 again)

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 Metabolism
• = sum total of all biochemical rxns in body
• Catabolism = degradation = bond breaking
– H2O is often consumed in this process (“hydrolysis”)
• “H2O is broken while other bonds are breaking, too”
– Examples:
• “Burning” fuel molecs
• Degrading worn-out structural molecs & enzymes (normal
turnover and renewal)
– Dominant during starvation

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GENERAL categories of catabolic enzymes
include:

• Anhydrases (remove H2O)

• ATPases
• Carbohydrases
• Proteases
• Lipases
• Nucleases
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Fig. 2.17: What is the substrate? What is the product? What category
enzyme? What is happening to water here? Is this a hydrolysis reaction?

Homework: How does Catabolism affect Osmolality? 12

Some basic catabolic pathways to know:
• Glycolysis (“glucose splitting”)
– Yields ATP and Pyruvate
• Glycogenolysis (“glycogen splitting”; Fig. 5.10)
– Yields single glucose molecs
• Lipolysis (“fat splitting”)
– Yields small lipids
• Proteolysis (“protein splitting”)
– Yields single amino acids

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 Metabolism
• = sum total of all biochemical rxns in body
• Catabolism = degradation = covalent bond breaking
– H2O is often consumed in this process (“hydrolysis”)
– “Burning” fuel molecs
– Degrading worn-out structural molecs & enzymes
– Dominant during starvation
• Anabolism = synthesis = bond making
– H2O is often made in this process (“metabolic water” is removed
from reactant = “dehydration”)
– Examples:
• Storing fuel molecs for later
• Replacing worn-out structural molecs & enzymes
– Dominant during growth & pregnancy
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GENERAL name for anabolic enzymes:

• Synthases

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Fig. 2.16: What is the substrate? What is the product? What category
enzyme? What is happening to water here? Why is it fair to call this a
“dehydration” reaction rather than a “hydrolysis” reaction?

Homework: How does Anabolism affect Osmolality? 16

Some basic anabolic pathways to know:
• Glycogenesis (“glycogen making”; Fig. 5.10)
– Stores glucose fuel molecs for later use
• Gluconeogenesis (“new glucose making”)
– Makes glucose fuel from other fuels (fats, AAs)
• Lipogenesis (“fat making”)
– Makes new structural lipids for cell membranes
– Stores fatty acid fuel molecs for later use
• Transcription (DNA → mRNA) followed by
• Translation a.k.a. Protein synthesis (mRNA →
protein)

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 Memory device for role of H2O

Growing babies are “juicy” Shrinking elderly are “dry”

(growth favors anabolism (aging/senescence favors
which liberates metabolic catabolism which consumes
water as byproduct) water by hydrolysis)

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 Fig 5.1
FUELS

Plasma
memb
O2 shortage
→ a few ATP per 1G

O2 abundant
Mito
heat membs
→ a few more ATP
Per 1G → a LOT more ATP per 1G
Krebs = Citric Acid Cycle
Figure
19.2
Illustrates
alternative
fuels

Plasma
memb

Cells “burn” Carbs using Mito

G(lycolyis), K(rebs) C(ycle), membs
and E(lectron) T(ransport)
C(hain).

Where do you see alternative

fuels “jumping in” to the + heat
default Carb pathway? 20
 Things to remember about fuels:
• “Every cell type uses glucose”
• Ability to use alternative fuels varies with cell type
• Pathology can alter fuel preference (heart failure
myocytes switch from fatty acids to ketones)
• LIVER can convert alternative fuels to glucose
(“Gluconeogenesis”) LIVER LIST ALERT!
• All fuels produce waste products, but some are
easier to handle than others

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 Storing fuel for a “rainy day”
• Glycogenesis: glycogen accumulation in cytoplasm
– Liver (glycogen → glucose into blood)
– Skeletal muscle (glycogen → glucose into cytoplasm for its
own “selfish” use)
– Brain astrocytes (glycogen → glucose → lactate sent to
neurons)
• Lipogenesis: fat droplet accumulation in cytoplasm
– Liver (triglycerides → fatty acids + glycerol into blood)
– White adipose tissue (triglycerides → fatty acids + glycerol
into blood)

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 Storing fuel for a “rainy day”
• Proteins do not “store” amino acids for
later, are made only to perform an
immediate function
– Excess AAs are converted by Liver to
Carbs or Fat for storage in Liver or
WAT
• DNA and RNA do not “store” nucleic acids
for later, are made only to perform an
immediate function
• Over-consumption of any type of fuel
leads to over-storage of fat droplets in
liver & WAT

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 Body’s “fuel molecs” in rough order of preference
(but varies by organ, see Table 5.4 on page 123)
1. Simple sugars e.g. glucose
2. Small lipids e.g. fatty acids
3. Ketone bodies
4. Lactate
5. Amino acids
AAs as fuel on a low
protein diet is “burning
the furniture”, as AAs
are no longer available
for protein synthesis.

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 Ketone Bodies

• Products of lipolysis
– A sign the body has moved to its 2nd favorite fuel
• Products of amino acid “de-amination” (Fig. 5.16)
– A sign the body has moved to its least favorite fuel, i.e.
the body is in real trouble with fuel availability
– “Dirty fuel” as get waste CO2 and NH3
• You already know what problem CO2 causes
• NH3 is ammonia; neurotoxic; LIVER uses ATP to quickly
convert it to harmless Urea (Fig. 5.16)
• “Ketoacidosis” may set in
• Scent of acetone (nail polish) on patient’s breath

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 Burning carbs aerobically, G/KC/ETC wastes seem
Figure
pretty easy to handle: lungs exhale CO2 + H2O,
19.2 urine removes H2O from the body, and heat
dissipates off exposed skin (acceleration provided
by sweating). BUT even these organ system
solutions don’t go far enough.

+ heat
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 WASTE HEAT
• Important: Blood carries heat
• Retained to warm the body
– More ways to warm up:
• Shivering thermogenesis (Skeletal Muscle reflex)
• Non-shivering thermogenesis (Brown Adipose Tissue)
• Increase Basal Metabolic Rate (Thyroid Hormone)
• Flushed to cool the body
– Vasodilation brings blood/heat to surface
– Sweating carries heat away

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WASTE LACTIC ACID: Fig 5.1
So far, we’ve considered burning carbs aerobically.
Burning carbs anaerobically, Glycolysis throws cells
a curveball: that detour to lactic acid. During
extreme exertion, Skel M dumps a lot of lactic acid
into the bloodstream “sewer”…
Lactic acid

Insufficient O2
Figure
5.11

Low O2

Per the “Cori Cycle”, the LIVER helpfully converts lactic

acid back to glucose and replenishes the blood’s glucose
concentration. Recently: brain neurons “love” LA and
use it even when there’s plenty of O2 around.
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Figure Nitrogenous Wastes: Because of their N atoms, AA
catabolism yields waste NH3 ammonia which is
19.2 dangerously neurotoxic

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• AAs contain –NH2 groups
– Cannot enter late G/early KC with –NH2 group still attached
• LIVER uptakes AAs & removes their –NH2 groups
– “De-amination” Fig. 5.16
• Results in ketone bodies (fuel) and NH3 ammonia
• Something similar happens when Nucleic Acids are catabolized
• Ammonia moves freely in the body and is quite toxic

AMMONIA

AMINO ACID KETO ACID

 LIVER to the rescue, again
• LIVER immediately uses ATP & other enzymes
to convert NH3 to non-toxic forms
• AA N-waste becomes “urea”
• NA N-waste becomes “uric acid”
From From AA de-
G+KC+ET amination ATP UREA
Enzymes
CO2 + NH3 + NH3 → H2O + CH4N2O

Homework:
Is urea formation a Catabolic or Anabolic reaction?
Is urea formation a Dehydration or Hydrolysis reaction?
Urea handling by kidneys
SECRETION
EXCRETION

RE-ABSORPTION

FILTRATION

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Your body’s biochemistry adjusts
based on physiological state
• Growth = emphasis on anabolism
• Injured or infected = emphasis on anabolism
• Absorptive state (food in stomach and/or
small intestine)
– 1st: digestive catabolism
– 2nd: storage anabolism (glycogenesis)
• Post-absorptive state (fasting, stomach &
small intestine empty)
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Where do you see Glucose hitting the bloodstream
as sugars are absorbed in the small intestine?

SetPt

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Fuel homeostasis during Post-absorptive state:

• E.g. between meals

• Pull 1st choice GLUCOSE out of storage
– Liver “mobilizes glycogen” (glycogenolysis) to put
glucose into blood
– Skel M “mobilizes glycogen” (glycogenolysis) for
itself only

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 Where do you see Glucose coming out
of storage into the bloodstream here?

SetPt

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 Fuel homeostasis during Post-absorptive state:
• Pull 1st choice CARBS out of storage. E.g. between
meals
– Liver “mobilizes glycogen” to put glucose into blood
– Skel M “mobilizes glycogen” for itself
• What if that’s not enough? E.g. low carb diet
• Pull 2nd choice LIPIDS out of storage
– Liver & WAT “mobilize lipids” (lipolysis) to put fatty acids into
blood
– Liver converts some lipids to ketones (ketogenesis) & puts
them into blood
• What if that’s not enough? E.g. starvation
– What follows may merit a trigger warning

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Starvation Dead at 21
from
massive
• Excessive AA catabolism → infection

Ammonia toxicity +
Ketoacidosis + Dehydration
• Protein loss = function loss =
skeletal AND heart muscle
weakness (heart failure),
kidney failure, immune
failure
• WAT loss → increased risk of
hypothermia, trauma to
joints and organs
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I’m not asking you to memorize this (useful) slide, but to take home
the message that PHYSIOLOGY INTEGRATES MULTIPLE SYSTEMS. The
material in this course will inevitably “build upon itself”.

Insufficient CARB fuel switches body to LIPID fuel and encourages KETONE BODY
formation in liver; KBs can serve as fuel or be excreted 41