Energy metabolism

Readings
Fox selections from Chapters 2, 4, 5, 6, and 11

"He said science was going to discover the basic secret of life someday," the bartender put in. He scratched his head and frowned. "Didn't I read in the paper the other day where they'd found out what it was?"
"I missed that," I murmured.
"I saw that," said Sandra. "About two days ago."
"That's right," said the bartender.
"What is the secret of life?" I asked.
"I forget," said Sandra.
"Protein," the bartender declared. "They found out something about protein."
"Yeah," said Sandra, "that's it."

-Kurt Vonnegut, Jr. Cat's Cradle

Overview

We will not get very technical on biochemistry of metabolism, since this is a physiology course and not a biochemistry course.

Reminder
Metabolism is the general term for two kinds of reactions:
(1) catabolic reactions (breakdown)
and
(2) anabolic reactions (constructive)

Organic Chemistry is the chemistry of carbon (C) which makes 4 bonds.
In "Star Trek" (the first movie), people were called "carbon based units" by the alien.

Carbohydrate

Fig. 2.13a (2.14a in 13th and 14th edition)
Carbohydrate (Carbo-hydrate is also sort of a compound word, carbon, "hydrate" suggests water) - the general formula is Cn(H2O)n
Monosaccharides
Hexose (hex = 6 [carbons], "-ose" always means sugar)- glucose, the most famous monosaccaccharide, is good to illustrate that monosaccharides usually assume a ring structure

Fig. 2.15 (2.16 in 13th and 14th edition)
Compound dehydration synthesis puts sugars together
Hydrolysis (hydro-water, lysis-breakdown) is the opposite.
In digestion, macromolecules are broken down to monomers.
Disaccharide - sucrose, lactose (milk)
Figure shows maltose and sucrose, and shows dehydration synthesis.

TRANSPARENCY from intro book
Polymerization Reactions: Condensation reaction and Hydrolysis

Fig. 2.14 (2.15 in 13th and 14th edition)
Polysaccharides starch (plant), glycogen (glyco-sugar, gen-give birth to) (animal)
Energy storage:
In liver for whole body
In muscle for muscle use

Fat

Fig. 2.19 (2.20 in 13th and 14th edition)
Lipids (fats) store more energy (2x sugar) 1 tablespoon of sugar is 50, fat 100 "Calories" = kilocaloriies
Glycerol & 3 fatty acids (16-24 C long) - triglyceride ester bonds , note the dehydration synthesis
The -COOH defines an organic acid such as a fatty acid, otherwise the molecule is a hydrocarbon.
C-C (single bond) vs. C=C (double bond) unsaturated (vs saturated with H's), with several, it is referred to as "polyunsaturated" PUFA = polyunsaturated fatty acid
Animal fats tend to be saturated, bad for arteries leads to atherosclerosis; vs vegetable fats better.
Polar phospholipids - we'll talk about that later, because our emphasis now is energy.
Steroids-cholesterol & hormones - we'll talk about that later, because our emphasis now is energy.
Salts of cholesterol are in bile (from liver) that acts like a detergent to emulsify fats to aid in digestion.

Protein

Fig. 2.27 (2.28 in 13th and 14th edition)
short = "Peptides", medium = polypeptide, long = "protein" (hundreds, thousands of amino acids)
The general formula is NH2-CR-COOH - amino ( -NH2 ) and acid ( -COOH ).
Peptide bonds involves -NH2 and -COOH getting linked with a dehydration synthesis.
There are about 20 amino acids (alphabet of 20 letters)
R group varies, see figure.
About half of the amino acids are "essential" meaning that they cannot be made by metabolic conversion from other molecules and thus need to be eaten
Structure:
1. primary (the sequence)
2. secondary (alpha helix, beta pleated sheet)
3. tertiary structure (disulfide and other bonds)
4. quaternary structure (chains interact with each other)
Here is a really important example - hemoglobin - which has 2 alpha subunits and 2 beta subunits and a heme group.

Figure 5.16
Important to the topic of energy in physiology, amino acids can be used for energy, nitrogenous waste must be eliminated as urea.

Biological energy

Fig. 4.15
ADP plus phosphate <-> ATP involved in storage and release of energy [typo on transparency, but o.k. in book]
ATP made of Adenine, ribose and 3 phosphates, energy stored in 3rd phosphate bond
It is interesting to note that ATP delivers it's energy by transferring its phosphate to molecules (you will see this several times in diagrams throughout the semester)

Energy - kinetic and potential (discussing bioelectricity, potential will also be Volts)
BTU's (British thermal units, which can be converted to calories) imply that energy and heat are related.
Heat stored in energies of covalent bonds in kcal / mol
Free energy can be used for work = what is stored in bonds minus what is wasted as heat
cellular respiration C6H12O6 -> 6CO2 +6H2O + energy
the free energy is 686 kcal/mol
ATP to ADP
38 of them generated when respiration is complete
40.3% efficient, the rest is heat, usually considered as waste but useful in temperature regulation in warm blooded animals, homoiotherms, homeotherms.

Reminder - "count" "calories"= kcal
2000 per day for a sedentary adult woman
Important that we do not lose calories (through urine or feces) except through urine in untreated diabetes.
Marathon - 3000 Cal aerobic. 100 yd dash -anaerobic

We get our energy mostly from (1) glucose, (2) glycogen (glyco-sugar, gen-give rise to) in muscle for use in muscle and in liver for glucose release to blood, (3) amino acids (with NH3 as waste), or (4) fat (mostly fatty acids are chopped down 2 carbons at a time to give acetic acid into acetyl CoA in the Kreb's cycle).
Photosynthesis to make glucose, cellular respiration to release energy
Reaction [for glucose, C6(H2O)6]: C6H12O6 + 6 O2 -> 6 CO2 + 6 H2O
Overall, 1 glucose can give up to 38 ATP's, a few from glycolysis and the rest from the mitochondrion

Glycolysis and anaerobic glycolysis

Background
It is important to introduce NAD+ plus 2 H <-> NADH in oxidation - reduction reactions as a way to carry electrons.
lose electrons - oxidation (NAD+ is oxidized)
nicotinamide adenine dinucleotide
add electrons - reduction (NADH is reduced)

Fig. 5.3
Glycolysis is a compound word glyco-sugar, lysis-splitting. Glucose is split into 2 pyruvic acids
Use 2 ATP's make 4, net 2 make 2 NADH's plus 2 H+'s, the H+'s come from from "sugar"

Fig 5.5 (5.10 in 13th and 14th edition)
Glucose in blood vs in cell

Fig. 5.4
This was covered in muscle lecture
without oxygen, make lactic acid.
Anaerobic glycolysis is used to deliver ATP quickly but wastefully (squandering glucose).
Make ATP's but need to regenerate NAD+ from NADH to make.
Lactic acid contributes to fatigue in muscle and oxygen debt, and the liver eventually reconverts.
Anaerobic cellular "respiration" is needed in times of extreme exertion because the heart (cardiac output) is the limiting factor in delivery of oxygen to muscle.

Polysaccharides
Glycogen - animal starch, polymer of glucose
High in muscle where it provides glucose for local use
High in liver where it provides glucose when fasting
Cellulose - cannot digest - "fiber"

Regulation by the hormone epinephrine (adrenalin)

Fig. 11.10
Epinephrine involved in stimulating liver to release glucose
Earl W. Sutherland, Jr. (from the US) won the 1971 Nobel Prize for mechanisms of hormone action.
It pertained to that beta adrenergic part and cAMP, a "second messenger" or part of a signal transduction "cascade."
So Sutherland is sometimes considered the founder of "signal transduction."
Note that there is a separate alpha adrenergic effect too

Glycolysis and the Kreb's cycle

Fig. 5.12
Pyruvic acids generate 2 acetic acids, become Acetyl CoA's.
Kreb's cycle = citric acid cycle = TCA (tricarboxylic acid cycle)
Takes place in the mitochondrion
A few ATP's are made plus NADH's and FADH2 are generated
CO2 is generated here.

The1953 Nobel prize in Physiology and Medicine was divided equally, one half awarded to: SIR HANS ADOLF KREBS for his discovery of the citric acid cycle and the other half to: FRITZ ALBERT LIPMANN for his discovery of co-enzyme A and its importance for intermediary metabolism.

sugar-H2 + NAD+ -> (DEHYDROGENASE) "sugar" + NADH + H+
(in other words, H is split to H+ and e-)
Electron transport and oxidative phosphorylation use oxygen
cytochromes - these are iron - containing pigments (iron is in the form of heme)
NADH and FADH2 give electrons to cytochromes and oxygen

Protons pumped, then flow down gradient making ATP's.
Something like an ion pump (we will covered that later in the semester) in reverse is how most ATP is made, H+ (pH, proton) gradient runs through that molecule, like water running through turbines generating electricity, to generate ATP

How does glucose get into the cell?

Fig. 6.16
(also covered in the membrane lecture)
Facilitated diffusion for glucose transport

Fig. 6.17
Insulin causes glucose transporters to be inserted to the membrane

Fig. 6.20
There is another kind of glucose transporter where Na+ (already pumped with ATP) drives it

Fig. 11.11
The receptor for insulin is a membrane spanning tyrosine kinase that dimerizes
Kinase means that the enzyme phosphorylates a protein
Tyrosine refers to the fact that phosphorylation is on tyrosine (an amino acid) residues.
Obviously, this would take place on the intracellular side of the membrane

Questions from 2004 - 2011 tests that pertain to this lecture

Glucose monomers can be linked either as starch or glycogen or differently, and people cannot digest this different polysaccharide. Answer either (1) What is this molecule called? or (2) Why can cattle and termites digest this molecule (while we cannot)?

cellulose, they have mutualistic microbial symbiotes

Compared with a saturated fatty acid, what must be missing from a carbon in a fatty acid that has a double bond to its neighboring carbon?

hydrogen

A hormone mediates the effect of the sympathetic nervous system to act on the liver cell for the release of glucose. Answer either (1) What hormone? or (2) If an increase in cAMP results from stimulation by this hormone, what kind of receptor to the hormone is used?

epinephrine (adrenalin), beta-adrenergic

The insulin receptor is an enzyme. What reaction does it catalyze?

a receptor tyrosine kinase adds a phosphate to the amino acid tyrosine

In digestion, monomers are broken out of polymers by hydrolysis. What is it called when monomers are put together?

dehydration synthesis

Regarding the carbohydrate in milk, answer either (1) What is that sugar called? or (2) Why is it thought that adult Caucasians of Northern European origin are more likely to be able to digest this sugar than adults of other ethnic origins?

(1) lactose (2) they evolved in the company of dairy husbandry

Glycerol is a 3 carbon chain with an alcohol (-OH) on each carbon. Each fatty acid that gets linked to glycerol has an acid (-COOH) group. How were the alcohols and acids altered to make the ester bond?

water was taken out

"Salts of Cholesterol" Answer either (1) What is the function? or (2) Where are they made in your body?

(1) emulsify fats (2) liver

Urea is manufactured in your body from carbon dioxide plus what waste?

NH3

Once glucose is split in half, there are two duplicate pathways leading to two respective pyruvic acids. Each limb generates 2 ATPs. Why, then, does glycolysis, as a whole, generate only 2 ATPs?

two ATPs were used up in glycolysis

Regenerating NAD (from NADH plus H+) is essential for what process?

anaerobic glycolysis

Adenylate cyclase converts (what?) into cAMP?

ATP

A hydrogen is split into H+ plus what?

an electron

Three fatty acids bound to glycerol by a dehydration synthesis (condensation reaction). What is this molecule?

fat = triglyceride

Salts of cholesterol - answer either (1) Why are they useful in digestion? Or (2) Where do they come from?

emulsify fats, liver

Why is the liver essential in getting rid of wastes generated by getting energy from amino acids?

that is where the reaction to make urea takes place

After glucose is chopped into two pieces, on the way to making two molecules of pyruvate, two ATPs are generated on each of the two reactions. Why is the value given for the number of ATPs made by glycolysis less than this value (this value equals 2 x 2 = 4)?

Two ATPs must be used

Name something other than pyruvic acid that can feed in to make acetyl CoA at the entrance to the Kreb's cycle.

amino acids, fatty acids, ketone bodies

"In other words, H is split into H+ plus (what?)".

an electron

Upon binding insulin, the insulin receptor, an enzyme, forms a dimer. Then what does this enzyme do?

it phosphorylates itself, it phosphorylates another protein

"Disulfide bonds hold together some places along the length of a protein." What level of organization is this?
 
tertiary
 
Glucose is taken up into a liver cell. During an ordinary day in your life, when does this happen?
 
After meals

What does the dehydration synthesis have to do with the comparison with monosaccharides and glycogen?
 
Puts units together in macromolecule
 
I rationalized that you might call a releasing hormone from the hypothalamus to the pituitary (through the portal system) a "peptide." Why peptide rather than protein?
 
Very short
 
Urea, answer one: (1) Referring to energy metabolism, why do we make this? Or (2) What are the precursors?
 
1 nitrogenous waste when a.a.used as calories 2 NH3 (ammonia) and carbon dioxide
 
"Fatty acids are chopped down two carbons at a time." Where, specifically, does this 2-carbon segment go to generate ATP.
 
Right to acetyl co-A in Krebs
 
When the insulin receptor dimerizes upon activation by insulin, answer either (1) What is the result of this enzyme's activity? (2) What molecule does this enzyme act on? Or (3) Where did the phosphate come from?
 
1 phosphate gets added to tyrosine 2 the insulin receptor itself 3 ATP

For cellulose, answer either (1) Describe it's structure. (2) How is it dealt with in your digestive system? Or (3) How do cattle and termites digest it?

a polymer of glucose with bonds that make it indigestible for humans, hence fiber, bulk. microbes in the guts of cattle and termites help them utilize this source of glucose

"The beta-adrenergic receptor crosses the membrane 7 times." Give (and justify) one level of protein structure (related to primary to quaternary) for this G protein coupled receptor.

primary (sequence of amino acids) of course, secondary - alpha helices

Epinephrine activates a beta-adrenergic receptor on the liver cell with the end point being the release of glucose to the blood stream. Give me one of the next two molecules downstream in this signal transduction cascade.

G protein, adenylate cyclase

"Protons run through a membrane molecule like water through a water wheel to generate ATP." Answer either (1) What was the energy source to create that proton gradient? Or (2) Where is this taking place in the cell?

electron transport in the inner mitochondrial membrane

For glucose transport across the membrane, answer either (1) How does insulin cause an increase [in glucose transport] for facilitated diffusion? Or (2) Why, for a different type of transporter, is energy (in the form of ATP) required?

more transporters (GLUT-4) are deployed to the membrane, for the sodium glucose cotransporter, sodium then needs to be pumped

What does a kinase do to a protein?

phosphorylates it

How does glucose get into a cell?

you need a membrane protein for diffusion

What is the activity of the insulin receptor enzyme?

tyrosine kinase

What is the polymer of glucose that is so important in muscle and liver metabolism?

glycogen

How is it that facilitated diffusion of glucose is increased by insulin?

more GLUT4 transporters deployed to membrane

The opposite of dehydration synthesis (condensation reaction) happens in digestion. What is this called?

hydrolysis

About how many ATPs do you get from full aerobic metabolism of one glucose molecule?

38

During anaerobic metabolism in muscle, what is pyruvic acid converted to?

lactic acid

What is the function of salts of cholesterol made by the liver and secreted into the small intestine?

emulsify fats

When I remind you that the insulin receptor is a tyrosine kinase, where is tyrosine and what happens to it?

on intracellular side of enzyme, tyrosine (amino acid) becomes phosphorylated

What second messenger activates protein kinase when the beta-adrenergic receptor of a liver cell binds epinephrine?

cAMP

In your body, what becomes of the amine of an amino acid if you use that amino acid for calories?

becomes ammonia that gets converted to urea

In your digestion, macromolecules are hydrolyzed. What is the name of the opposite reaction that had been used to string together monomers into a polymer?

dehydration synthesis

Arachidonic acid has 4 double bonds. What is the term for such a molecule?

polyunsaturated fatty acid

While fasting, what does the liver do with the glycogen it stores?

breaks it to glucose and sends that to the blood stream

How many pyruvic acids do you get from one glucose?

2

If a fatty acid were 14 carbons long, how many acetyl co-A's would be delivered to the Krebs cycle if it were chopped down completely in catabolism?

7

Epinephrine, acting on the beta adrenergic receptor, causes what to happen to glycogen in the liver?

breakdown to glucose and release to bloodstream

In addition to facilitated diffusion, there is a transport mechanism for glucose requiring energy delivery from ATP. To what molecule does ATP deliver its energy?

the sodium pump

In the biosynthesis of fat, to attach a fatty acid to glycerol via an ester bond, what molecule must be removed?

H2O

Fatty acids are "chopped down" two carbons at a time to feed into metabolism. Where do these two carbon components feed in (biochemically)?

acetate (acetyl CoA)

The need to regenerate NAD+ from NADH causes the formation of what from pyruvic acid?

lactic acid

What molecules are generated from the complete aerobic cellular respiration of glucose (in addition to energy)?

H2O and CO2

What are the salts of cholesterol of bile used for?

emulsify fats in digestion

Chemically, how is a polyunsaturated fatty acid different from a fully saturated fatty acid?

Double C=C bonds

What do we have to get rid of if we use amino acids for energy?

Nitrogenous waste

The hormone epinephrine (adrenalin) is sometimes considered the "first messenger" to signal the liver of the need to release glucose. Within the liver cell, what has been called the "second messenger" in this signal transduction cascade?

cAMP

What is urea made from and where does the body make it?

NH3 and CO2 in the liver

Describe the structure of hemoglobin in terms of protein subunits and the units where iron is located.

2 alpha and 2 beta protein chains each with a heme group

How is it that a liver secretion can emulsify fats to aid in digestion?

salts of cholesterol would have hydrophilic and hydrophobic sides

On the way to the Kreb's cycle, fatty acids are chopped down two carbons at a time to make what?

acetic acid or acetyl coA

"H is split to a proton and an electron." To achieve what?

to drive proton pump then capture energy of proton pump to make ATP

How can a cell's ability to take up glucose be so different with vs without insulin?

insulin causes the membrane deployment of transporters

What molecule donated the phosphate when insulin prompted the insulin receptor dimer to phosphorylate itself?

ATP

What would a beta adrenergic receptor on a liver cell mediate?

glycogenolysis

For one type of glucose transporter, not the facilitated diffusion, energy is required. How is that energy delivered?

when glucose is cotransported with Na+, the sodium pump

Carbon dioxide plus (what?) are converted into urea in the liver.

ammonia (NH3)

Polymers (macromolecules) are constructed from their building blocks by (what process)? (the opposite of how they are broken down in digestion)

dehydration synthesis (as opposed to hydrolysis)

"Salts of cholesterol" - relate to digestion. (Your answer could refer to an organ or a process.)

from the liver into the duodenum (small intestine) to emulsify fat

Sutherland's Nobel Prize winning work had cAMP as the "second messenger." For the "first messenger," what is the type of receptor on the surface of the cell?

beta adrenergic

How does fat feed into metabolism to render ATP? (An answer for either type of components that make up a fat will be OK.)

glycerol gets converted to the precursor of pyruvic acid. Fatty acids get chopped down 2 carbons at a time to become acetyl CoA

"You're not going to get carbon dioxide from anaerobic glycolysis" because it is made in what specific step?

Krebs cycle

Why would you ultimately need energy (ATP) for one type (which type?) of glucose transporter?

the one that uses sodium ions running down their concentration gradient - those ions need to get pumped back out

What use is made of protons (H+, hydrogen ions) running back down their concentration gradient (after they had been pumped up that gradient)?

This is the "water turbine" to generate ATP

"Tyrosine kinase" - where did the phosphate come from?

ATP donates the phosphate there (and pretty much everywhere)

Amino acids can be used for catabolic energy. Where do they feed into the metabolic mill?

Into pyruvic acid just before acetyl co-A

What would a beta adrenergic receptor on a liver cell mediate?

Via cAMP, increase conversion of glycogen to glucose

What does the dehydration synthesis have to do with the comparison with monosaccharides and glycogen?
 
Puts units together in macromolecule
 
I rationalized that you might call a releasing hormone from the hypothalamus to the pituitary (through the portal system) a >peptide.< Why peptide rather than protein?
 
Very short
 
Urea, answer one: (1) Referring to energy metabolism, why do we make this? Or (2) What are the precursors?
 
1 nitrogenous waste when a.a.used as calories 2 NH3 (ammonia) and carbon dioxide
 
"Fatty acids are chopped down two carbons at a time." Where, specifically, does this 2-carbon segment go to generate ATP.
 
Right to acetyl co-A in Krebs
 
When the insulin receptor dimerizes upon activation by insulin, answer either (1) What is the result of this enzymes activity? (2) What molecule does this enzyme act on? Or (3) Where did the phosphate come from?
 
1 phosphate gets added to tyrosine 2 the insulin receptor itself 3 ATP
 
For cellulose, answer either (1) Describe it's structure. (2) How is it dealt with in your digestive system? Or (3) How do cattle and termites digest it?

a polymer of glucose with bonds that make it indigestible for humans, hence fiber, bulk. microbes in the guts of cattle and termites help them utilize this source of glucose

"The beta-adrenergic receptor crosses the membrane 7 times." Give (and justify) one level of protein structure (related to primary to quaternary) for this G protein coupled receptor.

primary (sequence of amino acids) of course, secondary - alpha helices

Epinephrine activates a beta-adrenergic receptor on the liver cell with the end point being the release of glucose to the blood stream. Give me one of the next two molecules downstream in this signal transduction cascade.

G protein, adenylate cyclase

"Protons run through a membrane molecule like water through a water wheel to generate ATP." Answer either (1) What was the energy source to create that proton gradient? Or (2) Where is this taking place in the cell?

electron transport in the inner mitochondrial membrane


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