Biochemistry: Generation Of Energy From Fatty Acids, Ethanol And Amino Acids

Front 1

What's the basic structure of a fatty acid?

Back 1

Unbranched hydrocarbon chain with a carboxy group at the end.

HOOC-C-C-C-C-C-C

Front 2

Does a fatty acid carry a charge at physiological pH?

Back 2

They are deprotonated, have a negative charge.

Front 3

Are fatty acids with an odd number or carbons found in humans?

Back 3

Yes, but mostly even numbers because acetylcoA is 2 carbons.

Front 4

What does amphipathic mean?

Back 4

Partially hydrophobic (carbon chain) and partially hydrophilic (carboxy)

Front 5

What are the three major classes of fatty acids and their lengths?

Back 5

Short = 2-4 carbons
Medium = 6-10 carbons
Long = 12 carbons

Front 6

What are the two ways of describing the position of double bonds in fatty acids?

Back 6

Delta9= C9=C10
Omega9, same only counting from the omega carbon (last carbon)

Front 7

How many carbons in butyric acid?

Back 7

4

Front 8

How many carbons in lauric acid?

Back 8

12 (found in coconut oil, mammary milk)

Front 9

How many carbons in palmitic acid? What's the unsaturated counterpart?

Back 9

16 Palmitoleic acid

Front 10

How many carbons in stearic acid? What's the unsaturated counterpart?

Back 10

18 Oleic acid, linoleic acid, a-linolenic acid.

Front 11

What's a omega 3 fatty acid? What's a omega 6 fatty acid?

Back 11

Omega 3: a-linolenic acid
Omega 6: Linoleic acid

Front 12

Why is micelle formation spontaneous?

Back 12

Hydrophobic part is shielded from water in a micelle.

Front 13

What's a fatty acid with 20 carbons and four double bonds?

Back 13

Arachidonic acid

Front 14

What's the difference between cis and trans double bonds?

Back 14

Cis (on the same side)- bond forms angle of 120

Trans (on opposite sides)- favors extended shape of hydrocarbon chain.

Front 15

What is likely to be more solid at body temperature? A low melting point fatty acid, or high melting point?

Back 15

High melting point (above body temperature)

Front 16

Which configuration is usually found in nature?

Back 16

Only fatty acids with cis double bonds are formed.

Front 17

Where are trans fatty acids found?

Back 17

Man made products

Front 18

What two factors decrease melting temperature?

Back 18

Increase in double bonds, decreased number of carbons.

Front 19

What is the structure of a triacyl glycerol?

Back 19

Three fatty acids attrached to a glycerol backbone. Usually the middle FA is unsaturated while the other two are saturated.

Front 20

How does epinephrine mobilize fat? Where does it work?

Back 20

Binding to receptor uses ATP to create cAMP, which then activates protein kinase A, which will turn a bunch of proteins into phosphoproteins, activating the fat mobilizing proteins, and inhibiting the fat synthesizing proteins.

Fatty tissue

Front 21

What does glucagon do?

Back 21

Same thing as epinephrine but in liver.

Front 22

Generally, what pathways are suppressed by epinephrine and glucagon?

Back 22

Glycolysis and glycogen synthesis

Front 23

Generally, what pathways are stimulated by epinephrine and glucagon?

Back 23

Lipolysis, gluconeogenisis, glycogen breakdown

Front 24

True/False: Increased cAMP in cell = glucose is in short supply?

Low cAMP = glucose is plentiful?

Back 24

True

Front 25

True/False: Enzymes involved in fat (and glycogen) synthesis and storage are inactivated in the phorphorylated state and that enzymes involved in fat (and glycogen) mobilization and catabolism are activated in de-phosphorylated state?

Back 25

True

Front 26

What does perilipin do in the the regulation of fat metabolization?

Back 26

Perilipin in the unphorphorylated state surrounds and protects a fat droplet. In the phosphorylated state, it is removed from the fat droplet. cAMP--> Protein Kinase A can phosphorylate it.

Front 27

What is the metabolic function of fat mobilization?

Back 27

Provides energy for gluconeogenesis in liver (during fasting).

Front 28

How are free fatty acids transported in blood?

Back 28

Albumin

Front 29

What do epinephrine and norepinephrine do?

Back 29

Activation of hormone-sensitive lipase in adipose.

Front 30

What does insulin do?

Back 30

Inactivation of hormone sensitive lipase, stimulates protein phosphatase activity.

Front 31

How do long chained fatty acids get into the membrane?

Back 31

Carnitine forms an ester bond with long chain fatty acids (replacing the CoA) using carnitine-palmitoyl transferase I, it gets shuttled across the membrane, in the membrane, the Co-A gets put back on and carnitine removed by Carnitine-palmitoyl transferase II.

Front 32

How to short and medium chain fatty acids get into the membrane?

Back 32

Can diffuse right through.

Front 33

What inhibits Carnitine-palmitoyl transferase I?

Back 33

Malonyl-CoA
** Think, where is this from?

Front 34

Where does B-oxidation occur?

Back 34

Mitochondrial matrix

Front 35

How are free fatty acids metabolically activated?

Back 35

By being bound to CoA and enzymes on the ER membrane and the outer mitochondrial membrane.

Front 36

What are the four steps of beta oxidation?

Back 36

Acyl-CoA --(Acyl-CoA DH)--> trans-delta2 enyol CoA --> 3L-hydroxylacyl-CoA --(B-hydroxyacyl-CoA DH)-> 3 ketoacyl-CoA --(B-ketothiolase + CoA-SH)--> acetyl CoA + acyl CoA (goes through the process again)

Front 37

What does each cycle of beta oxidation produce?

Back 37

1 acetyl CoA
1 FADH2
1 NADH
1 n-2 acyl-CoA

Front 38

Which end does beta oxidation happen?

Back 38

Alpha end (COOH)

Front 39

What coenzyme is required for acyl-CoA dehydrogenase?

Back 39

FAD --> FADH2

Front 40

What coenzyme is required for b-hydroxylacyl dehydrogenase?

Back 40

NAD --> NADH

Front 41

What does thiolase do? What are the products? What are the fates?

Back 41

Severance of the bond between alpha and beta carbons by adding another CoA

Acyl-CoA- goes back through the process

Acetyl-CoA- sent to Kreb's cycle

Front 42

How is beta oxidation regulated?

Back 42

By the supply of fatty acids. If fatty acids get out of the fat cell, they are going to get oxidized. In adipose tissue, lipase is regulated. If there is liver pathology, they can pile up in the liver by re-esterification and it creates a fatty acid.

Front 43

What are the different acyl-CoA dehydrogenase?

Back 43

Long- works down to C12
Medium- works down to C4
Short splits it into 2 acetyl CoA

Front 44

What happens with carnitine deficiency?

Back 44

Produces fasting nonketotic hypoglycemia and heart arrhythmias. Can be treated with carnitine or medium chain triglycerides

Front 45

What happens with medium-chain acyl-CoA dehydrogenase deficiency?

Back 45

Free fatty acids are oxidized to 10-12 carbons. Produces fasting nonketotic hypoglycemia and muscle weakness. Dangerous only in extreme or frequent fasting.

Front 46

How do unsaturated fatty acids enter the beta oxidation pathway?

Back 46

Normal beta oxidation until double bond. Then, the double bond is modified to resemble trans-enoyl CoA intermeidate via isomerase enzyme. Then it can enter normal beta oxidation.

You don't generate FADH2 this way, and you use NADPH instead of NADH.

Front 47

What are the intermediates involved in odd-chain free fatty acid oxidation?

Back 47

Beta oxidation until there are three left:
Propionyl-CoA ------> D-methylmalonyl-CoA <---> L methylmaloynol CoA ---> Succinyl CoA

Front 48

How is methylmalyonyl CoA converted to succinyl CoA? Where else have you seen succinyl CoA?

Back 48

Methylmalyonyl-CoA mutase: B12

TCA cycle.

Front 49

What is the last CoA derivative produced by beta oxidation of odd numbered free fatty acids?

Back 49

Propionyl-CoA

Front 50

How is Propionyl-CoA coverted to methylmalonyl-CoA? What vitamin cofactors are involved? Is it energy requiring?

Back 50

Propionyl-CoA carboxylase: Biotin (Vit. H or B7) binds CO2, uses ATP.

Front 51

What is Refsum's Disease?

Back 51

Deficiency in alpha-oxidation (single carbon removal from COOH end of a long (C>20) Free fatty acid. It can also remove methyl groups from free fatty acid.

Accumulates phytanic acid (fatty acid with a bunch of methyl groups) and produces abnormal neurologic symptoms.

Front 52

What is the substrate for peroxisomal betal oxidation? What is produced? (Also, what is not produced?)

Back 52

Very long chained free fatty acids (20-26C)

No NADH produced, but it is shortened enough for the mitochondria to metabolize.

Produces H2O2, which is degraded by catalase.

Shortens the FFA into octanoyl-coA.

Front 53

How are ketone bodies formed?

Back 53

Two acetyl coAs are joined together by B-ketothiolase (same enzyme as the last step of b oxidation?) and it loses one of the coA's. The product is called acetoacetyl-coA.

Another acetyl group is added with HMG-CoA synthase to make HMG-CoA.

Then it is split by HMG-CoA lyase into acetoacetate (ketone body) and acetyl-coA

Acetoacetate uses NADH to make D3-hydrobutyrate (ketone body) using B-hydroxybutyrate dehydrogenase.

Front 54

Whta are the two different fates of HMG CoA?

Back 54

Acetyl coA, Acetoacetate (ketone body)

Front 55

What steroid is made from HMG coA?

Back 55

Cholesterol

Front 56

What limits the entry of acetyl CoA into the citric acid cycle, eventually leading to its conversion into ketone bodies? What phisological conditions will lead to this limiting condition?

Back 56

Citrate
Excessive fatty acid oxidation (acetyl-coA shifted to ketone bodies)
Starvation or low car diets.

Front 57

Why don't ketones form in carnitine deficiency?

Back 57

You can't form ketones if you can't burn fats. (not a sufficient amount of acetyl coA?)

Front 58

What does HMG CoA Synthase do?

Back 58

It adds on another acetyl group (from acetyl-coA) onto acetoacetyl-coA to make HMG-coA (3 hydroxy 3 methyl glutaryl coA)

Front 59

What does HMG CoA Lyase do?

Back 59

It splits HMG-CoA into acetoacetate and acetyl-coA

Front 60

What does HMG CoA Reductase do?

Back 60

It makes cholesterol from HMG-CoA

Front 61

What are the two fates of acetoacetate?

Back 61

It can be made into 3-hydroxybutyrate or it can spontaneously give off a CO2 and make acetone, which can be breathed out through the lungs.

Front 62

How are ketone bodies (acetoacetate and d3hydroxybutryate used?

Back 62

They are converted to energy in extrahepatic tissues.

Front 63

How is acetoacetate converted to acetoacetyl-coA in peripheral tissues?

Back 63

It goes to the peripheral tissues from the blood and is combined with succinyl-coA. *** the liver lacks the enzyme to do this.

The products are acetoacetyl-coA and succinate. B-ketothiolase (b-oxidation) then adds another SH-CoA to make 2 acetyl-coA to be used in the TCA cycle.

Front 64

Which amino acids can be converted to acetyl-coA? Which physiologic conditions would accelerate this conversion?

Back 64

Leucine and isoleucine can directly be converted to acetyl-coA

Alanine, cystine, glycine, serine, threonine, tryptophan can be converted via pyruvate

Starvation, fasting, block of B-oxidation and fat mobilization. (Any process that results in a lack of acetyl-coA.

Front 65

How can amino acids provide carbon skeletons for glucose synthesis?

Back 65

Any amino acid that can be fed into the TCA cycle can eventually be converted to malate which then can enter gluconeogenesis.

Front 66

What are two ways ethanol metabolism can contribute to acidosis?

Back 66

Ethanol metabolism produces a lot of NADH, which drives lactate dehydrogenase and malate dehydrogenase in the "wrong" direction. This inhibits gluconeogenesis (from pyruvate --> OAA --> PEP). It produces lactate and malate.

Ethanol → Acetaldehyde → Acetate → Acetyl CoA → Ketone bodies

Front 67

Which two-carbon metabolite is produced from ethanol oxidation in the cytoplasm? What is produced by further oxidation in the mitochondrion?

Back 67

Cytoplasm:
Ethanol---->Acetaldehyde
Makes NADH, using alcohol dehydrogenase.

Mitochondrion:
Acetaldehyde -----> Acetate
Makes NADH using aldehyde dehydrogenase.

This then can be made into acetyl-coA using GTP, and coA.

Front 68

What are three types of acids produced from ethanol metabolism?

Back 68

Lactate
Fatty acids
Ketones

Front 69

How can ethanol metabolism produce hypoglycemia?

Back 69

Ethanol produces a lot of NADH, which stimulates the formation of lactate. It depletes pyruvate levels which depletes OAA levels. Because this is the pathway to gluconeogenenisis, there is hypoglycemia during periods of fasting.

Front 70

What's the only other source of glucose from the liver?

Back 70

Amino acids.

Front 71

Why can ethanol metabolism lead to an elevation in VLDL?

Back 71

Increased levels of NADH will increase the conversion of DHAP to glycerol-3-phosphate. This increased synthesis of triacylglycerol means increased VLDL and increased storage of triacylglycerol in liver.

Front 72

How are ketones used?

Back 72

Extrahepatic energy source
During fasting, large amount of free fatty acids are released. Acetyl-CoA formed by β-oxidation is not readily used for biosynthesis during fasting. Oxidation by TCA cycle is minimal because NADH and FADH2 formed during β-oxidation provide enough fuel for respiratory chain.
HMG-CoA synthase = rate limiting enzyme of ketogenesis. Powerfully stimulated by fasting, dietary fat, fatty acids, and insulin deficiency.