TBL-11 Fatty acids

Question 1

in beta oxidations of unsaturated fatty acids, A Δ3-cis double bond is isomerized to a Δ2-trans double by _______ enzyme

Answer 1

A Δ3-cis double bond is isomerized to a Δ2-trans double bond using the enzyme

Δ3-cis → Δ2-trans- enoyl-CoA isomerase

Question 2

Handling of Δ4-cis Double Bonds:

what enzymes handle delta 4 bonds ?

Answer 2

Δ4-cis-fatty acids or Δ4-cis-enoyl-CoA derivatives enter the β-oxidation

• A reduction step converts Δ3-trans-enoyl-CoA to Δ2- trans-enoyl-CoA, facilitated by

dienoyl-CoA reductase

and an NADPH is needed

Question 3

what do we get from an odd chain of fatty acids?

Answer 3

propionyl-Coa which enters the citric acid cycle, which become succinyl Coa

Question 4

When do kentone bodies form?

Answer 4

during fasting or low carb intake

Question 5

ketone bodies?

Answer 5

acetoacetate, acetate( breath out with CO2, spontanous

D-3-hydroxybutyrate made with NADH and H

Question 6

enxyme that makes D-hydroxybutyrate from Acetate?

Answer 6

D-hydroxybutyrate dehydrogenase

This enzymatic activity depends on the mitochondrial NAD+/NADH ratio

Question 7

well-fed mammals blood levels of ketone bodies_______ mol/L

Answer 7

well-fed mammals blood levels of ketone bodies are typically below 0.2 mmol/L

Liver is the main site of ketone body production but does NOT use them significantly

Question 8

ketone bodies leave the body through

Answer 8

urine or breathing

Question 9

what are the steps and enzymes involved in the formation of ketone bodies from acetyl coA?

where are the HMG enzymes found?

Answer 9

step1: two acetyl coa are joined together by thiolase and it is called

acetoacetyl-CoA

step 2: acetocetyl- CoA is joined to another actyl- CoA by

3-Hydroxy-MethylGlutaryl-CoA (HMG-CoA synthase )

forms 3-Hydroxy-MethylGlutaryl-CoA

then 3-Hydroxy-MethylGlutaryl-CoA is split by HMG-CoA lyase

this produces acetoacetate

3. acetoacetate is then converted into 3-D-hydroxybuterate by 3-D-hydroxybuterate dehydrogenase

mitochondia of liver

Question 10

how are ketone bodies used outside the the liver?

Answer 10

acetoacetate get an CoA group attached to it by

succinyl-CoA-acetoacetate-CoA tranferase

and become acetoacetyl-CoA which then is broken down by thiolase which will make 2 acetyl CoA

Question 11

Regardless of feeding state, the liver extracts about _______of
the FFAs passing through it

Answer 11

Regardless of feeding state, the liver extracts about 30% of
the FFAs passing through it

triacylglycerols are the main precursor to ketone bodies

Question 12

Regulation of Ketogenesis and how can this idea help diabetics?

Answer 12

• Mobilization of FFAs from adipose tissue is a key regulator
  of ketogenesis
• Regulating FFA levels and their mobilization from adipose tissue can be a potential therapeutic for diabetic ketoacidosis

maybe by blocking CPT-1

Question 13

how does the fed state vs the starvation state regulate CPT-1 ?

Answer 13

CPT-I activity is low during the fed state, which reduces fatty acid oxidation and promotes esterification (building of triacylglycerols from FA)

fed state will prodcue high levels of Malonyl CoA (during fatty acid synthesis) and will inhibit CPT-1

low levels of malonyl coa will increase FA oxidation

Question 14

how does Serum FFA Levels influence ketosis :

Answer 14

Influence of Serum FFA Levels:
* When serum FFA levels are elevated, a larger proportion of acetyl-CoA is directed towards
ketogenesis

Ketogenesis is a less efficient pathway in terms of ATP yield but allows for increased oxidation of FFAs (produce NADH AND FADH2 that could make ATP in ETC)

Question 15

factors that can influence ketogenesis

Answer 15

low levels of OOA, high NADH/NAD+ ratio from beta oxidation, low blood glucose

Can push acetyl-CoA towards ketogensis

Question 16

Carnitine Deficiency

occurrence
symptoms
treatment

Answer 16

Carnitine Deficiency:

Newborn Infants

• Occurrence: Commonly seen in newborns, especially preterm infants, due to inadequate synthesis or renal leakage
• Symptoms: Hypoglycemia due to impaired fatty acid oxidation and muscle weakness from lipid accumulation
• Treatment: Oral supplementation of carnitine

Question 17

Carnitine Palmitoyltransferase (CPT) Deficiency:
* CPT-I Deficiency:

• CPT-II Deficiency:

Answer 17

• CPT-I Deficiency: Primarily affects the liver, leading to reduced fatty acid oxidation and ketogenesis, resulting in
  hypoglycemia
  (primary site of ketosis is liver so remember CPT-1 liver primar)
• CPT-II Deficiency: Mainly impacts skeletal muscle

Question 18

Jamaican Vomiting Sickness:

Answer 18

• Caused by consuming unripe fruit of the AKEE tree, which contains hypoglycin that inactivates acyl-CoA
  dehydrogenase (cant transport the FA inside the mito), leading to hypoglycemia

Question 19

During fatty acid biosynthesis: acetyl-CoA turns molonyl-coA by_______ and requires biotin

Answer 19

acetyl CoA carboxylase (ACC)

biotin

malonyl is unique to FA synthesis

Question 20

what are the two groups in fatty acid synthase complex?

Answer 20

Cysteine sude chain (ketoacyl synthase): transfters the molonyl and cetyl coA

Phosphopantetheine chain (acyl carrier protein) , carries the growing fatty acid

Question 21

what are the steps in Fatty acis synthesis?

Question 22

since acetyl CoA cant leave the innermembrane of mitochondria, how do we get actyl coA in the cytosol for Fatty Acid Synthesis?

Answer 22

Citrate leave the mitochondria by shuttle

citrate turns into OOA and Acetyl CoA by cytoplasmic ATP-citrate lyase

inner mito has carriers for citrate, pyruvate and malate, not for OOA or acetyl CoA

Question 23

more insuline and carbohydrate levels____

Answer 23

increase acetyl Coa and increase fatty acid synthesis

Question 24

what is the role of SREBP-1c and ChREBP in regulating fatty acid synthesis (ACC and fatty acid synthase)

Answer 24

Sterol regulatory element binding protein 1c (SREBP-1c)

• Liver X receptor (LXR) stimulates SREBP1 gene
• Dietary polyunsaturated fatty acids (PUFA) inhibits SREBP1 gene

Carbohydrate response element binding protein (ChREBP)

• Glucagon activated cAMP inhibits ChREBP
• Low energy activated AMP activated protein kinase(AMPK) inhibits ChREBP

Question 25

ACC is _____ by citrate and ______ by acyl CoA fatty acids (beta acid oxidation)

Answer 25

citrate and inhibited

Question 26

Acetyl-CoA carboxylase two forms:

Answer 26

• ACC1 cytoplasmic enzyme in liver, adipose tissue,
  and lactating mammary glands
• ACC2 enzyme of the outer mitochondrial membrane

Question 27

enzyme responsible for fatty acid activation for Beta oxidation

Answer 27

Acyl CoA synthase needs ATP

Question 28

describe the process of FA transfer into the mitochondria from cytosol for Beta oxidation

Answer 28

Acyl gets a CoA added by acyl synthase (thiokinase)

then carnitine binds to acylCoA which CPT 1 then removed the actylCoA and carnitine goes into the the intermembrane and then through the inner membrane through Cartine-acyl carnitine translocase

then CPT II will add the CoA again and beta acid oxidation will begin.

Question 29

steps of beta oxidation