M1 Biochemistry: The Fat Economy

Front 1

How many kcal of energy on average do we get from the following:

A. glucose
B. glycogen
C. fat

Back 1

A. glucose (4 kcal/g dry wt) ~ 10 kcal
B. glycogen (4 kcal/g dry wt) ~ <1,000 kcal
C. fat (9kcal/g) ~ >100,000 kcal

Thus, fat is the predominant source of energy production (60-80% of 2,000 kcal/day).

Front 2

Where do fatty acids that we use in beta-oxidation come from?

Back 2

- Dietary lipids (Triacylglycerol, Phospholipids, Cholesteryl esters)
- Triacylglycerols in the blood (mainly from VLDL and chylomicrons, but also possibly from LDL and HDL)
- Intracellular stores of esterified fatty acid (Adipose tissues, Cytoplasmic lipid droplets, Membranes)

The sources (usually triglycerides) of fatty acid are extramitochondrial and often located at a distance from the tissues where they are to be β-oxidized.

Front 3

The principal sources of fatty acid are relatively inert, hydrophobic complex lipids, which are suitable for storage or transport but not themselves substrates for Beta oxidation.Consequently, enzymes called_____ are required to make the fatty acids available for oxidation.
What are the classes of that enzyme?

Back 3

lipases

There are 3 major classes of triglyceride lipases:
Pancreatic lipase (breaks down trigylcerides in diets)
Lipoprotein lipase (breaks down triglycerides in fat)
Adipose tissue (hormone sensitive) lipase

Front 4

Of the three major classes of triglyceride lipases, name those that hydrolyze a single ester bond from each triacylglycerol molecule.

Back 4

Lipoprotein lipase and hormone sensitive lipase. Other lipases hydrolyze the remaining ester bonds.

Front 5

What is triacylglycerol broken down into after lipoprotein lipase or hormone sensitive lipase acts upon it? From there, what do other lipases break those products down into? What is the rate-limiting step?

Back 5

After LPL and HSL, triacylglycerol is broken down into 1 fatty acid and 1 diacylglycerol. Then Lipase acts on that and turns that diacylglycerol into fatty acids and glycerol.

Front 6

Which of the following enzymes is most active when a patient is fasting?

A. Pancreatic lipase
B. Lipoprotein lipase
C. Adipose tissue (hormone sensitive) lipase

Back 6

C. Adipose tissue (hormone sensitive) lipase that is stimulated by glucagon.

Pancreatic lipase is stimulated by bile acids and LPL by insulin.

Front 7

Remember, FAs are usually released by lipase activity at a site remote from where it will eventually be meatabolized. Which of the following transport pairs is correct:

A. Esterified FAs via VDL, chylomicrons ; Unesterified FAs via serum albumin and other FA binding proteins
B. Esterified FAs via serum albumin and other FA binding proteins ; Unesterified FAs via VDL, chylomicrons

Back 7

A. Esterified FAs via VDL, chylomicrons ; Unesterified FAs via serum albumin and other FA binding proteins

Front 8

[ Esterified / Unesterified ] fatty acids are not substrates for beta-oxidation. Most pathways that metabolize F.A.s require activation to _______________.

Back 8

Unesterified DAs ; fatty acyl-CoA

Front 9

Once acyl-CoA is made, it cannot cross the mitochondrial membranes by itself but needs ___________.

Back 9

The carnitine shuttle system.

CAT I : acyl-CoA -> acyl-carnitine which is shuttled across mitochondrial membranes to matrix.

Once inside, carnitine acyltransferase II reverses the reaction and we end up with acyl-CoA again.

Carnitine shuttle is an important site of regulation for beta-oxidation.

Front 10

What type of fatty acids do NOT use the carnitine shuttle?

Back 10

medium chain fatty acids! They just cross the membrane! Inside the mito matrix, there is a FA CoA synthestase that will process it for beta-oxidation.

Front 11

Write out the mitochondrial beta-oxidation pathway with structures, enzymes, and any additions as well as byproducts.

Back 11

Front 12

Fatty Acyl CoA dehydrogenases are chain length specific! What are the symptoms and lab findings for individuals with medium chain fatty acyl dehydrogenase deficiency?

Back 12

Metabolic acidosis, elevation of MCFA, dicarboxcylic acids and fatty acyl-carnitines in blood. Pts are severely fatigued and hypoglycemic after just a few hours of fasting.

Front 13

Beta-oxidation is regulated by the following mechanisms. Elaborate on each.

A. Covalent modification
B. Allosteric inhibition
C. Transcriptional regulation

Back 13

A. Covalent modification refers to lipase, which dictates the source and availability of fatty acids.

B. Allosteric inhibition refers to the fact that CAT I can be inhibited by malonyl-CoA, a byproduct of FA biosynthesis

C. transcriptional regulation refers to PPARs (peroxisomal proliferator activation receptors) that bind fatty acids (and drugs and fibrates for hyperlipdemia). The activated PPAR then binds to PPARE in gene promoter regions, inducing transcription).

Front 14

Pancreatic lipases
A. break down triglycerides in diets
B. triglycerides in fat
C. are hormone sensitive

Back 14

Pancreatic lipases break down triglycerides in DIETS

Front 15

Lipoprotein lipases
A. break down dietary triglycerides
B. have products that are taken up by muscle as an energy source or adipose tissue for storage as fat
C. are hormone sensitive

Back 15

Lipoprotein lipases have products that are taken up by muscle as an energy source or adipose tissue for storage as fat

Front 16

Adipose tissue lipases
A. break down triglycerides in diets
B. break down triglycerides in VLDL and chylomicrons
C. are hormone sensitive

Back 16

Adipose tissue lipases are hormone sensitive

Front 17

This lipase digests triglycerides in the DIET and is activated by bile acids with which it is secreted from the common bile duct.

A. Pancreatic lipase
B. Lipoprotein lipase
C. Adipose Tissue (Hormone sensitive) lipase

Back 17

A. Pancreatic lipase

Front 18

This lipase hydrolyzes triglycerides being transported by chylomicrons and VLDL in the blood. It is activated by insulin.
A. Pancreatic Lipase
B. Lipoprotein Lipase
C. Adipose Tissue (Hormone Sensitive) Lipase

Back 18

B. Lipoprotein lipase.

Front 19

This lipase hydrolyzes triglycerides stored in adipose tissue. It is activated by glucagon or epinephrine.
A. Pancreatic Lipase
B. Lipoprotein Lipase
C. Adipose Tissue (Hormone Sensitive) Lipase

Back 19

C. Adipose Tissue (hormone sensitive) lipase

Front 20

Why are fatty acids converted by fatty acyl-CoA synthetases into fatty acyl CoA?

Back 20

Unesterified fatty acids are not substrates for β-oxidation. With few exceptions, pathways that metabolize fatty acids require activation to fatty acyl-CoA.

Front 21

What is this the reaction for? What enzyme is used? Why is this reaction important?

Back 21

Unesterified fatty acids are not substrates for β-oxidation. With few exceptions, pathways that metabolize fatty acids require activation to fatty acyl-CoA.

Front 22

Where does the activation of fatty acids by fatty acyl-CoA synthestase occur?

Back 22

Mitochondrial outer membrane (for long chain fatty acids destined for beta oxidation)
Inner mitochondrial membrane ( for medium chain fatty acids destined for beta oxidation
ER (for long chain fatty acids for biosynthetic pathways "discussed later")

Front 23

Name the three lipases and what each is activated by and on what types of triglycerides they act upon.

Back 23

Pancreatic: activated by bile acids, works on dietary triglycerides.
Lipoprotein: activated by insulin, works on triglycerides in VLDL and chylomicrons
Hormone Sensitive: activated by glucagon or epinephrine, works on tirglycerides in adipose tissue

Front 24

How many Acetyl-CoAs and ATPs would be yielded in how many rounds from beta-oxidation of Palmitoyl-CoA?

Back 24

8 Acetyl-CoAs from 7 rounds of beta oxidation which thus yields 7 FADH2 and 7 NADH. Since each FADH2 is worth 1.5 ATPs and each NADH is worth 2.5 ATPs, the total is 28 ATPs and 8 Acetyl CoAs in 7 rounds!

general: Acetyl CoAs are N/2 and # of rounds/FADH2/ NADH will be equal to N/2 -1

Front 25

Beta oxidation of branched chain or odd numbered fatty acids can occur as long as....

Back 25

the beta-position is not blocked by substitution or steric hinderance. If it is, then isomerases work on it first then it continues normally.

Front 26

Why is oxidating an odd chain fatty acid considered glucogenic and not ketogenic?

Back 26

odd chain fatty acids end up with a propinoyl-CoA instead of Acetyl-CoA when it comes to the last reaction. That Propinoyl-CoA gets turned into succinyl-CoA and goes to the TCA cycle. Anything that goes on to the TCA cycle is considered glucogenic.

Front 27

Were are very long chain fatty acids (more than 20 carbons) beta oxidized?

Back 27

in peroxisomes (they are not good substrates for mitochondrial beta oxidation)

It is very similar to mitochondrial pathway except for the exception that reducing equivalents from fatty acyl-CoA dehydrogenase is donated to oxygen to produce H2O2 without FADH2 (and thus, eventual ATP production).

Front 28

Ketogenesis is triggered by...

A. high insulin: glucagon ratio
B. high glucagon: insulin ratio

Back 28

B. high glucagon: insulin ratio

Front 29

When utilized in peripheral tissues, 3-oxybutyrates what enzymes are needed?

Back 29

Front 30

True or False:
Ketogenesis occurs under normal conditions and is a significant source of 3-oxybutyrates for energy production in peripheral tissues in all metabolic states.

Back 30

TRUE.

Front 31

____________ become major substrates for energy production in peripheral tissues (particularly the brain) during prolonged fasting or starvation. hint: think ketogenesis

Back 31

3-oxybutyrates

Front 32

Why do individuals with uncontrolled Type I diabetes experience ketosis and ketonuria?

Back 32

In Type I DM, insulin insufficiency results in a massive mobilization of fat, leading to production of 3-oxybutyrates which overwhelms the capacity to use them. The acidic 3-oxybutyrates accumulate in the blood and other tissues (ketosis), upsetting the acid-base balance and are cleared in the urine (ketonuria). Urinary excreition of potassium bound to 3-oxybutyrates may also lead to potassium depletion. Similar though less severe effects may occur with Type II diabetics.