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BioChem Exam 3 > Lipid Metabolism > Flashcards

Lipid Metabolism Flashcards

1
Q

what is the major source of carbon for fatty acid synthesis?

A

dietary carbons

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2
Q

fatty acid synthesis overview

A

occurs in liver
secondarily in adipose, brain, kidneys, lactating mammary glands

requires coordination btwn cytosolic and mitochondrial rxns

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3
Q

precursor and end product of FA synthesis

A

acetyl coA 2C

palmitic acid 16C

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4
Q

list the 3 phases of fatty acid synthesis

A
  1. cytosolic entry of acetyl coA
    - –made in mito matrix but needed in cytoplasm
  2. generation of malonyl coA
    - –acetyl coa is carboxylated to malonyl coA
    - –most important substrate in FA synthesis
    - –***rate limiting rxn
  3. fatty acid chain formation
    - –FA synthase catalyzes 7 rxns to incorporate acetyl coa and malonyl coa into palmitate
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5
Q

list the first 4 steps in FA synthesis

A
  1. condensation of acetyl coa w/ oxaloacetate = citrate
    - –citrate synthase
  2. transport of citrate from mito to cytosol
    - –via citrate lyase
  3. citrate converted back to acetyl coa and OAA
    - –citrate lyase
    - –acetyl coa can now be used for FA synthesis in cytosol
  4. OAA reduced to malate
    - –malate dehydrogenase
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6
Q

steps 5 and 6 of FA synthesis

A
  1. malate transported into mito via malate a-ketoglutarate transporter
    - –oxidized to OAA
    - –malate dehydrogenase
  2. cytosolic malate converted to pyruvate
    —malic enzyme
    pyruvate transported to mito via pyruvate transporter
    —carboxylated to OAA by pyruvate carboxylase
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7
Q

presence of citrate and insulin will ______ FA synthesis while glucagon, epinh, high [AMP], palmitate, PUFA will ______ synthesis

A

increase

decrease

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8
Q

conversion of acetyl CoA to malonyl CoA by carboxylation

A

catalyzed by acetyl coa carboxylase ACC

**rate limiting enzyme of fatty acid synthesis

ACC adds CO2 to acetyl coa

  • -uses ATP
  • –uses biotin as cofactor
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9
Q

malonyl CoA

A

regulator — inhibits carnitine acyltransferase
**rate limiting step in FA degradation

prevents FA synthesis and degradation from occurring simultaneously

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10
Q

regulators of phase 3 in FA synthesis

A

promoters:
insulin
glucocorticoid hrs

inhibitory
PUFA

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11
Q

describe FA chain formation

A

2 C from malonyl coa are sequentially added to growing FA chain

  • –occurs in 7 rxns
  • –forming palmitate (16:0)

these rxns occur on FA synthase complex (FAS complex)

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12
Q

FAS

A

multi-enzyme complex

composed of 2 dimers arranged head to tail

each has 7 enzyme activities
an acyl carrier protein ACP

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13
Q

palmitate synthesis

A

1 acetyl coa + 7 malonyl coa + 14 NADPH + 14 H+

CH3(CH2)14COO- + 14 NADP+ + 8 CoA + 6H20

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14
Q

what is the purpose of reduction rxns in the FAS reactions?

A

using dehydration of NADPH to remove double bonds

creating a fully saturated growing FA

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15
Q

what are the sources of NADPH?

A

malic enzyme = 1

PPP = 2-12

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16
Q

list the 7 rxns in FA synthesis for creating palmitate

A
  1. acetyl ACP
  2. malonyl ACP
    - –condensation
  3. acetoacetyl ACP
    - –reduction
  4. D-3 hydroxbutyryl ACP
    - –dehydration
  5. crotonyl ACP
    - –reduction
  6. butyryl ACP
  7. palmitate

occurs 7x total = C16

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17
Q

list the main rxns of the 3 phases in FA synthesis

A
  1. ATP citrate lyase
    citrate —> acetyl coa + OAA
  2. acetyl coa carboxylase
    **rate limiting step
    acetyl coa + CO2 —> malonyl coa
  3. FA synthase
    4C FA - repetition —> 16C palmitate
18
Q

regulation of ATP citrate lyase

A

stimed by phosphorylation

gene expression induced by glucose/insulin

gene expression inhibited by:
PUFA
leptin

19
Q

PUFA

A

polyunsaturated FAs

20
Q

regulation of acetyl CoA carboxylase

A

inactive dimer – active polymer

  1. allosteric regulation
  2. phosphorylation/De-phos
  3. induction
21
Q

allosteric regulation of acetyl coa carboxylase

A

citrate +

long chain FA/palmitate -

22
Q

phosphorylation control of acetyl coa carboxylase

A

phos = +
insulin

de-phos = -
epinh
glucagon
AMP

23
Q

control of gene expression induction - acetyl coa carboxylase

A

gene exp up regulated by high carb/low fat diet

24
Q

regulation of FAS

A

allosteric reg — presence of phosphorylated sugars increases activity

gene expression control:
+ = insulin, glucocorticoid hrs, high carb/low fat diet
- = high fat diet, starvation, PUFA

25
Q

synthesis of longer chain FA

A

elongation of palmitate
occurs in SER or mito
occurs 2C at a time
NADPH has reducing power

brain cells need longer FA chains C18-24

26
Q

carbon donors for longer chain FA synthesis

A

SER uses malonyl coa

mito uses acetyl coa

27
Q

desaturation of FAs

A

inducing double bonds

occurs in SER catalyzed by acyl coa desaturases

humans can add DB btwn carbons: 4-5, 5-6, 6-7, 9-10
but humans cannot make 9-10 DBs must ingest thru diet as omega 3/6 FAs

28
Q

essential fatty acids

A

humans cannot make w-3 or w-6 FAs

must ingest their precursors as:
linoleic acid
linolenic acid

29
Q

nomenclature of FAs

A

based on position of carbon from methyl end = omega end

6C away from methyl = w-6

30
Q

what is the importance of not being able to create DBs between the 9-10 carbons?

A

these fatty acids are very important for development and functioning

ex. EPA and DHA

31
Q

eicosanoid hormones

A

arachidonate
FA derived from linoleate
major precursor for signal molecules

prostaglandin
yields 9 major classes of prostaglandins called PGA to PGI

32
Q

describe eicosanoid hormones

A

local short lived hormones

influencing activities of cells
inflammation
blood flow
ion transport
synaptic transmission
induce sleep
33
Q

clinical example of eicosanoid hormone

A

aspirin blocks enzyme that converts arachidonate into prostaglandin

blocking this step interferes w/ signaling pathways
such as: inflam, fever, pain, blood clotting

34
Q

major storage form of FAs

A

triacylglycerol or TAG
have almost 7x more nrg than carbs

a glycerol head
3 FA chains attached

35
Q

sources of TAGs

A

diet
processed in intestines

hepatocytes and adipocytes

36
Q

perilipin

A

family of proteins that coat lipid droplets in adipose and muscle cells

regulate lipolysis by controlling physical access to TAGs

are regulated by PKA

overexpression of perilipin1 inhibits lipolysis
KO peilipin increases it **used for obesity treatment

37
Q

first phase of FA activation

A

occurs in cytosol
need to get FA into mito but the memb is not permeable to FAs

acyl-coa synthetase traps FA in cells
—making it metabolically active

38
Q

translocation to mito matrix

A

carnitine converted to acyl carnitine

  • –which can be moved into mito
  • –via carnitine acyltransferase II

acyl carnitine can be converted back to carnitine in mito
—via carnitine acyltransferase II

39
Q

4 steps of B-oxidation

A
  1. oxidation
    acyl coa dehydrogenase
  2. hydration
    enoyl coa hydratase
  3. oxidation
    3-hydroxyacyl coa dehydrogenase
  4. thiolysis
    acetyl coa acetyltransferase

**these steps are repeated until FA broken down into acetyl coa

40
Q

the 4 main steps of B-oxidation generate?

A

FADH2 (14)
—delivers e- to ETC

NADH (21)
—delivers e- to ETC

acetyl coa (96)
---enters TCA cycle

14+21+96 = 131
2 ATP used
= 129 net ATP

41
Q

ketone bodies

A

water soluble, acidic compounds

  1. acetoacetate
  2. B-hydroxybutyrate
  3. acetone

produced in liver only
provide nrg for tissues and brain during fasting/starvation

42
Q

utilization of acetoacetate

A

acetoacetate to acetoacetyl coa
—coa transferase

to 2 acetyl coa
—thiolase

BioChem Exam 3 (10 decks)

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