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FA Metabolism Flashcards

1
Q

Pamitate synthesis:
where does it happen?
from what?
elongated where?

A

in cytosol from acetyl CoA,

elongated in ER

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2
Q

Where does fatty acid oxidation occur?
Oxygen required?
Oxidized to what?

A

in mitochondria, oxygen required (aerobic);

oxidized to acetyl-CoA

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3
Q

Where does fatty acid synthesis occur?
Oxygen required?
Oxidized to what?

A

in cytosol:

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4
Q

What happens to fatty acids during starvation and DM?

A

fatty acid oxidation –> ketone bodies produced by liver (not good long term – fatal)

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5
Q

Gluconeogenesis is dependent on fatty acid _________.

A

oxidation

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6
Q

Describe the ways in the which the structure of the FAs differ

A

chain length and #/shape of double bonds

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7
Q

What is the difference btwn sat and unsat fats?

cis/trans bond

A

of double bonds

almost always of cis config

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8
Q

What is the role of essential FAs in prostaglandin synthesis?

A

x

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9
Q

What is the role of dietary omega-3 FAs?

A

anti-inflammatory effect

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10
Q

What is the role of dietary omega-6 FAs?

A

form the backbone of Pro inflammatory prostaglandin precursors

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11
Q

What is the role of acetyl-CoA carboxylase in FA synthesis?

A

site of regulation: first enzyme of pathway

ABC carboxylase: combining one CO2 with one acetyl CoA

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12
Q

What is the role of FATTY ACID SYNTHASE in FA synthesis?

A

catalyzes remaining several rxns in FA synthesis:

Acetyl-CoA + malonyl-CoA –> 4 C fatty acid

  • requires 2 molecules of NADPH, repeats until chain reaches 16C = palmitic acid
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13
Q

How are long chain FAs synthesized?

A

repeated condensation of two carbon units

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14
Q

What is the favored formation ___ in most tissues?

A

16-carbon palmitate: saturated FA

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15
Q

What are the co-factors required for FA synthesis?

A

x

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16
Q

What are the sources of reducing equivalents (NADPH) for FA synthesis?

A

x

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17
Q

How are FA chains elongated? Where?

A

mitochondira or ER

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18
Q

What co-factors are required for FA chain elongation?

A

acetyl-CoA Carboxylase requires Biotin, vit B7 as cofactor

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19
Q

What chemical alterations are made to the molecule after FA chain elongation?

A

x

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20
Q

How are FA chains desaturated? Where?

A

ER

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21
Q

What co-factors are required for FA chain desatuation?

A

acetyl-CoA Carboxylase requires Biotin, vit B7 as cofactor

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22
Q

What chemical alterations are made to the molecule after FA chain desaturation?

A

x

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23
Q

What are the short term regulators of FA synthesis?

A

Citrate;

Palmitoyl CoA = long chain Fatty acyl-CoA

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24
Q

What is the mechanism by which citrate regulates FA synthesis?

A

allosterically ACTIVATES acetyl CoA carboxylase by promoting formation of large (active) polymers
short term

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25
What is the mechanism by which palmitoyl CoA regulates FA synthesis?
INHIBIT enzyme by breaking down polymers (short term reg)
26
What are the long-term regulators of FA synthesis?
insulin; glucagon
27
What is the mechanism by which insulin regulates FA synthesis?
STIMULATES acetyl CoA carboxylase by dephosphorylation (vis protein phosphatase) (high-carb diet or fat-free diet stimulate FA synth through increased synth of acetyl CoA carboxylase)
28
What is the mechanism by which glucagon(/epi) regulates FA synthesis?
INHIBITS acetyl CoA carboxylase through cAMP-mediated phosphorylation (via AMPK) (think high-fat diet or fasting causes high glucagon)
29
How does FA and TAG biosynthesis integrate into mainstream carb metabolism?
x
30
How is the integration of FA and TAG biosynthesis regulated?
x
31
What are the sources of acetyl-CoA for FA synthesis?
x
32
What are the glycolytic intermediates used in TAG synthesis?
x | eg: DHAP
33
What is the effect of insulin deficiency/insufficency on acetyl-CoA levels?
x
34
How are TAGs synthesized?
x
35
What are the starting products of TAG synthesis?
x
36
What are the intermediates of TAG synthesis?
x
37
What are the final products of TAG synthesis?
x
38
How are TGs synthesized in liver different from TGs synthesized in adiopose?
x
39
How are TAGs catabolized to FFAs + Glycerol?
x
40
What is the rate of the metabolites of TAGs catabolized to FFAs + Glycerol?
x
41
How are FFAs transported in the blood?
x
42
How are FFAs activated and transported into the matrix of the mito for breakdown to obtain energy?
x
43
What is the role of the carnitine shuttle for LCFA (long chain fatty acids)? (why is a shuttle necessary to cross the mito membrane?)
get long chain fatty acids into the mito for beta oxidation
44
What is the role of lipoprotein lipase in TG breakdown?
x
45
What is the role of CAT-1? (CPT I)
CYTO (outer leaflet of mito) converts Fatty acyl CoA to acyl carnitine (Acyl carnitine is the transported into the mitochondrial matrix via CAT)
46
What is the role of CAT-2? (CPT II)
MITO (inner leaflet) cleaves carnitine and makes fatty acyl CoA for beta oxidation within mitochondrial matrix
47
What does CAT do and where does it live?
Lives between the mitochondira membrane - shuttles acyl carnitine from cyto to mito matrix - shuttles carnitine from in mito matrix to cyto
48
What is the regulatory role of malonyl-CoA?
x
49
What is the fate of carnitine?
x
50
What is the sequence of events of FA oxidation in mito?
x
51
Explain: General features of oxidation pathway of unsat odd-chained FAs
x
52
Explain: General features of oxidation pathway of branched-chain FAs
x
53
What are the 3 compounds termed "ketone bodies"?
x
54
How is #1 formed in liver mito?
x
55
How is #2 formed in liver mito?
x
56
How is #3 formed in liver mito?
x
57
What is the mechanism of formation of ketone bodies?
x
58
What are the physiological roles for ketone bodies?
x
59
What are the pathological roles of ketone bodies?
x
60
How does overproduction of ketone bodies lead to ketosis? ketoacidosis?
x
61
What are the pathological conditions of ketosis? ketoacidosis?
x
62
What is the mechanism by which hormonal activation of lipolysis in adipose tissue is coordinated with activation of gluconeogenesis in liver during fasting?
x
63
Compare and contrast FA synthesis vs degradation at the level of: -organ involvement
x
64
Compare and contrast FA synthesis vs degradation at the level of: -physiological regulation?
x
65
What occurs with deficiencies in FA metbolism?
x
66
MCAD deficiency
x
67
CPT-I deficiency
relatively rare, affect liver primarily; lead to FA oxidation and ketogenesis Sx: hypoketotic hypoglycemia; elevation in blood levels of carnitine; hepatomegaly; muscle weakness
68
CPT-II deficiency - 3 main forms
1) adult myopathic form (muscle pain; fatigue, myoglobinurina following exercise) 2) severe infantile multisystem form (manifest in first 6-24 months) - hypoketotic hypoglycemia; progress to severe hepatomegaly and cardiomyopathy 3) neonatal (lethal; rare) - sx in hours/days after birth; respiratory failure; hepatomegaly; seizures; hypoglycemia; cardiomegaly --> fatal arrhythmias
69
name characteristics of: impaired oxidation of medium-chain FAs
ACCUMULATION OF DICARBOXYLIC ACID AR; hypoketotic hypoglycemia; presents in infancy; high concentration of: Medium-chain carboxylic acids, acyl carnitines; and dicarboxylic acids (due to omega oxidation) in plasma and urine - hyperammonemia (result of liver damage) - hypoglycemia (inability to metabolize fats during fasting: limits gluconeogenesis) NB: deficiencies in short and long-chain FA DH have similar clinical features
70
How is MCAD treated?
frequent feeding, avoidance of fasting, carnitine supplementation
71
What are the causes and effects of accumulation of methylmalonyl-CoA?
CAUSES: - Vit B12 def - defect in Intrinsic Factor - Defect in mutase enzyme (methylmalonyl CoA mutase) EFFECTS: methylmalonyl acidurea maybe: peripheral neuropathy * can be used to differentiate btwn folate and B12 def
72
What intermediate in the oxidation of odd-chain FAs is likely to appear in the urine in vit B12 deficiency?
methylmalonic acid
73
What is the most likely underlying cause for pt rhabdomylosis?
carnitine palmitoyltransferase II deficiency (CPT II)
74
Why can't liver use ketone bodies?
it lacks CoA transferase
75
How do we use ketone bodies as alternate fuel?
acetoacetate--> Acetylacetyl CoA --> 2 acetyl CoA --> TCA cycle (oxaloacetate)
76
How is ketone body synthesis regulated?
NAD+ is reversing the TCA cycle: converting oxaloacetate to malate which can be used for gluconeogenesis --so need build up of acetyl coA and slowing down of TCA to get formation of ketone bodies
77
What does the heat muscle prefer to use as an energy source?
acetoacetate
78
When do we use ketone bodies as an alternate fuel?
fasting or diabetes or | -high in lipids with low in carbs lntake
79
What does the brain prefer to use as an energy source? What can it use?
prefers glucose; | can use acetoacetate during starvation/diabetes
80
What can lead to hypoketotic hypoglycemia?
Defects in: - carnitine transporter (can't get long chain FAs into cell from plasma to cyto as long chain Fatty acyl CoA ) - CPT I - CAT - CPT II - Fatty acyl CoA DH - Acetyl CoA (mitochondria type; not cytosolic bc cytosolic is for cholesterol)
81
Describe ketone body formation process
long chain FAs from adiopose tissue, broken down after Hormone sensitive lipase action ----> get into cyto via CARNITINE TRANSPORTER --> get into mito (via CPT I, CAT, CPT II) --> reduced to acetyl CoA via fatty acyl CoA DH --> ketone bodies
82
What ketone bodies are increased in diabetics?
acetoacetate, D-beta-hydro
83
Why do chronic alcoholics get fatty liver disease?
Alcohol inibits expore of VLDL from liver to blood.
84
What is the effect of insulin with respect to glycolysis in liver and Lipoprotein lipase in Blood/adipose?
stimulates: LIVER: glucose -(via glycolosis)-> DHAP --> Glycerol 3-P --> TAG --> VLDL) insulin also stimulates LPL allow more update of 3 FA CoA in adipose to convert to --> TAG
85
What is the pathway for activating Hormon-sensitive lipase?
ADIPOSE Glucagon (epi) --> activate adenlyl cyclase --> cAMP --> PKA --> HSL activated to get into lipid droplet to hydrolyse TAG to monoacylglycerol --> MGL / FA --> adipocyte --> circulation --> myocyte --> beta oxidation/TCA/respiratory chain --> ATP + CO2 + Serum albumin
86
Acyl-CoA DH
can have specificity for different FAs -uses FAD (to FADH2) to oxidize the beta
87
beta ox
1:16
88
Which will yield more ATP: | an 18C FA with unsat (double bond) at position 9 or position 6?
Unsat at Position 9 (bc unsat at even posiiton results in loss of 3 ATP)
89
What enzyme is required to absorb biotin in diet?
biotinase (remove covalently bound biotin from proteins in diet)
90
How does Biotin deficincy slow FA production?
The formation of malonyl-CoA via acetyl-CoA carboxylase requires biotin as a cofactor NB: citrate lyase, malic enzyme, FA synthase do not require biotin for their activity

GI (17 decks)

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