FORM & FUNCTION (Fat Synthesis)

Question 1

fatty acids (FA)

Answer 1

-simplest form of lipids
-long chains of aliphatic hydrocarbons with a carboxylic acid
-saturated (no double bonds) vs. unsaturated
-basic components of many things
-rarely ‘free’ (FFAs) in biological systems
*usually esterfied in storage

Question 2

FAs basic components of

Answer 2

-triglycerides (fat storage)
-lipoproteins (fat transporter molecules)
-glycerolphospholids (membrane constituents)
-ketone bodies (soluble fat for energy)
-cholesterol (hormone, vitamin, bile acids)
-eicosanoids (signalling molecules)

Question 3

FA stored

Answer 3

-commonly esterified
-stored as triacylglycerol (3FFA + 1 glycerol)
-can not form end to end like CHO

Question 4

Triacylglycerol (triacylglycerol)

Answer 4

-as close as lipids come to form polymers
-cannot join end to end
-can aggregate into large globules=storage depot for fat

Question 5

FFA

Answer 5

-free FA
-fatty acid not attached to glycerol (in an ester linkage)

Question 6

FA synthesis

Answer 6

-starting material is acetyl-CoA
*liver is major site of FA biosynthesis
1. Converts acetyl-CoA to FA
2. Exports them for storage in adipose

Question 7

Sources of Acetyl-CoA

Answer 7

-amino acids
-CHO
-lipid
*excess of these are synthesized and stored as fat

Question 8

Acetyl-CoA translocation

Answer 8

-FA synthesis takes place at the cytoplasm
-Acetyl-CoA is found in mitochondria
*utilize citrate shuttle to bring acetyl-CoA back into the cytoplasm
-change Acetyl-CoA to citrate, through citrate shuttle then back to Acetyl-CoA

Question 9

Carboxylation reaction

Answer 9

-first and rate-limiting step of of FA synthesis
*catalyzed by Acetyl-CoA carboxylase (ACC)
-reaction requires a carboxybiotin group that is formed by biotin carboxylase
*first intermediate product is Malonyl-CoA

Question 10

Acetyl-CoA carboxylase (ACC)

Answer 10

-first step is physiologically irreversible
-allosterically and hormonally controlled

Question 11

ACC allosterically controlled

Answer 11

-activated by citrate: starting material
-inhibited by palmitoyl-CoA: end product
*self regulated

Question 12

ACC hormonally controlled

Answer 12

*reversible phosphorylation
-dephosphorylated: active
>insulin (high nutrient state): protein phosphatase 1
-phosphorylated: inhibited
>glucagon/E, high AMP (low energy state): AMP kinase

Question 13

Fatty acid synthase (FAS)

Answer 13

-start with 1 acetyl-CoA + 1 malonyl-CoA: each attached to FAS
-cycle repeats (6x) until FA synthesis is complete, adds 1 malonyl-CoA (2C) each time

Question 14

Palmitate (16:0)

Answer 14

-common product of fatty acid synthesis
-basic precursor for other fatty acids
*free FA are esterified to from triglycerides (can form lipid bilayers: structural constituents of the cell)

Question 15

Basic FA precursor: modifications

Answer 15

1. Desaturase: addition of double bonds
2. Elongase: extension beyond 16 carbon

Question 16

FA biosynthesis summary

Answer 16

-excess nutrients (mostly CHO) are utilized as precursors
-regulated by acetyl-CoA carboxylase (hormone sensitive)
-palmitate (16:0) is the basic precursor for many FA derivatives
*all taking place in liver

Question 17

Triglycerides (TG)

Answer 17

-FFA are stored as TGs
-begins with glycerol-3-phosphate
-addition of 3 FA acyl-CoA to produce TGs

Question 18

Glycerol-3-phophate

Answer 18

-part of storing FFA as TGs
1. Phosphorylation of glycerol by glycerol kinase (liver & kidney)
2. Reduction of dihydroxyacetone phosphate from glycolysis (adipose)

Question 19

TG transport

Answer 19

-TG are mainly synthesized in the liver
-insoluble
-requires interaction with lipoprotein complexes to transport in plasma & between tissues

Question 20

Classes of lipoproteins

Answer 20

1. Chylomicrons (CM)
2. Very low density lipoproteins (VLDL)
3. Intermediate/low/high density lipoproteins

Question 21

chylomicrons

Answer 21

-transports exogenous fat (from diet)

Question 22

VLDL

Answer 22

-transports endogenous fat (made by body)

Question 23

IDL, LDL, HDL

Answer 23

-breakdown products of VLDL&CM

Question 24

Lipoprotein structure

Answer 24

-hydrophilic head and proteins make lipoproteins soluble

Question 25

Lipoprotein lipase (LPL)

Answer 25

1. Apoproteins on lipoproteins (VLDL or Chylomicron) interact with LPL anchored on endothelial surface of capillaries
2. LPL breaks down lipoproteins to release contents (ex. TG)
3. FFA binds to albumin in blood
4. VLDL transports TG away from liver, return as LDL or IDL (VLDL remnants)
   *LPL activity is activated by insulin

Question 26

FFA + albumin

Answer 26

-transported via CD36 (fat receptor) into adipose tissues (storage) or muscle (energy use)
-FFA + albumin cannot cross the blood brain barrier

Question 27

Density of lipoprotein

Answer 27

-density: protein to lipid ratio
-TG levels decrease as lipoproteins are catabolized
>increasing relative ratio of protein to lipid

Question 28

Lipoprotein sources

Answer 28

-CM: intestine
-VLDL: liver
-LDL: plasma
-HDL: liver, intestine

Question 29

Lipoprotein transport summary

Answer 29

1. TGs synthesized in liver are packaged into VLDL for export
2. VLDL circulate in blood and are cleaved by lipoprotein lipases on capillary wall to release FFA
3. FFA are bound by albumin (transported to muscle and adipose)
4. Cleaved VLDL become IDL and LDL is returned to liver

Question 30

FFA re-esterification (adipose)

Answer 30

-FFA (glycerol + FFA) are re-esterified to triacylglycerol in the adipose tissue for storage
-adipose tissues lack glycerol kinase
>glycerol-3-phosphate must come from plasma glucose

Question 31

Insulin: FFA re-esterification (muscle)

Answer 31

-insulin stimulates GLUT 4 which transports glucose into adipose tissue

Question 32

Insulin regulation of FA metabolism

Answer 32

1. Activate ACC via dephosphorylation
2. Activate LPL to increase lipoprotein breakdown in plasma: transports triglyceride into tissues
3. Activate GLUT4 to promote glucose uptake in adipose, required for triglyceride synthesis

Question 33

Hyperlipidemias: (excess lipid in blood)

Answer 33

-elevated levels of TG levels
-lactescent(milky) serum = elevation of TG (either CM or VLDL bound)
-caused by diabetes mellitus, hypothyroidism or Cushing’s disease
-common in miniature schnauzers
-LPL deficiency reported in inherited hyperlipidemia of New Zealand cats

Question 34

Hyperlipidemia observed after high fat diet

Answer 34

-cloudiness due to elevated chylomicron (fat from diet)

Question 35

If cloudiness persists after fasting

Answer 35

-due to high levels of VLDL (endogenous fat)