Fat Metabolism Flashcards
___ ___ ___ ____ can generate a lot of acetyl CoA. In the liver, Acetyl CoA from beta-oxidation can be used to synthesize ___ ____, which other tissues can use as a metabolic fuel.
Fatty acid beta-oxidation
Ketone bodies
Fatty acid beta-oxidation occurs in the ____. It has the the highest ____ generating potential compared to other metabolic pathways.
Mitochondria
Energy
Fatty acids consumed in the diet and synthesized de novo are stored in ____ as _____.
Adipocytes
Triacylglycerides
- Short chain fatty acids: ___ or less carbons
- Medium chain fatty acids: ___ to ___ carbons
- Long chain fatty acids: ___ to ___ carbons
- Very long chain: __ or more carbons
6
6 to 12
13 to 21
22
____ fatty acids are solid at room temperature. _____ (double bonds) fatty acids have a lower melting point.
Saturated
Unsaturated
____ and ___ fatty acids are essential in the diet.
Linoleic
Linolenic
____ ___ ____ cuts the first fatty acid from triglyceride to make diacylglyceride. ___ ___ ____ then cuts off the remaining fatty acids.
Adipocyte triglyceride lipase
Hormone sensitive lipase
Adipocyte triglyceride lipase cuts the first fatty acid, forming ___ which is transported into the cytoplasm by ___ ___. The fatty acid transporter is a complex with ____.
Palmitate
Serum albumin
CD36
Insulin ____ hormone sensitive lipase. Glucagon ____ it.
Inhibits
Activates
Fatty acids are transported into the cytoplasm by binding the extracellular Ligand domain of ____, this domain is composed of ____ amino acids to facilitate binding to fatty acids.
CD36
Hydrophobic
Palmitate is activated by linkage to _____. This reaction is catalyzed by ____ ____ ___ ____. There are different synthetases for different chain lengths
CoASH
fatty acyl CoA synthetase
palmitoylCoA must cross the impermeable ___ ____ ___ in order for Beta-oxidation to take place. This occurs via ____ ___.
Inner mitochondrial matrix
Carnitine shuttle
____ ____ is transported across the inner mitochondrial membrane
Fatty acylcarnitine
In the fasted and starved states, the body wants to ____ fatty acids and the carnitine shuttle is ___.
Burn
Active
____ ____ ____ I is a major regulator of fatty acid catabolism. Malonyl CoA is an Allosteric _____ of CPT I. Insulin promotes the production of malonyl CoA. ____ inhibits the production of malonyl CoA by inhibiting ___ ___ ___ (ACC).
Carnitine palmitoyl transferase
Inhibitor
AMPK
acetyl CoA carboxylase
CPT I deficiency is an inherited autosomal recessive disorder. It is the failure to import fatty acids into the ____, resulting in ____ ____ in the fasted state.
Diagnosis: increased free ___, ___, and free ___ ___ in the blood.
Mitochondria
Hypoketotic hypoglycemia
Carnitine, acyl-CoA, and fatty acids
CPT II is also an inherited autosomal recessive disorder. Three types:
1. Adult onset: characterized by ___ pain, ___, and ____ after prolonged exercise or fasting
2. Neonatal onset
3. Infant onset
Both are characterized by ____, ___, and often fatal.
Diagnosis: increased long chain ___ ___ ___ molecules in the blood.
Muscle
Weakness
Myoglobinuria
Hypoglycemia
Irritability
Fatty Acyl Carnitine
Beta oxidation of fatty acids is a multiple step process. In each cycle, two ___ of the fatty acid chain are oxidized to ___ ___.
4 steps:
___, ___, __, and ___
Carbons
acetyl-CoA
Oxidation, hydration, oxidation, cleavage
Palmitoyl CoA:
The ___ carbon is the first carbon away from the functional group. The ___ carbon is the second carbon away from the functional group.
Alpha
Beta
Beta oxidation of long chain fatty acids overview:
At the end of beta oxidation of long chain fatty acids, one acetyl CoA can be used in the ___ ___, producing a total of ___ ATP.
TCA cycle
10
There are a total of ___ acetyl CoA molecules made from 1 mol of palmitoyl. ___ FAD and ___ NADH are made. Leading to a total of ___ ATP.
8
7
7
106
Summary of beta-oxidation of palmitate:
Beta oxidation of a twenty carbon fatty acid such as ___ ___ yields ____ ATP.
Stearic acid
134
Medium chain Acyl CoA dehydrogenase deficiency (____) is frequent in northwestern European ancestry. It presents in infants with fasting ____ ___, hepatic encephalopathy, and sudden death.
Diagnosis: elevated medium chain ____ in the blood.
Prognosis: if identified before severe hypoglycemic episodes it’s okay. Fasting tolerance improves with age.
MCAD
Hypoketotic hypoglycemia
Acylcarnitine
____ ___ ___ has a similar presentation to MCAD. It occurs after eating unripe ackee fruit which contains ____, which inhibits medium and short chain acyl CoA dehydrogenase.
Jamaican vomiting sickness
Hypoglycin
In summary, during fasting, the decreased insulin/glucagon ratio stimulates ___ ___ ___ to free fatty acids from triacylglycerols stores in adipose tissue. The free fatty acids then travel to energy requiring tissues where they undergo ___ ___ in the mitochondria to produce energy.
Hormone sensitive lipase
Beta-oxidation
The ____ cannot use fatty acids as fuel because they can’t cross the ___ ___ ___. Instead, the liver converts fatty acids into ___ ___, which can be used in the brain.
Brain
Blood brain barrier
Ketone bodies
Regulation of ketone body synthesis:
In the fasted state, hepatocytes do not consume much ___. Increased levels of beta-oxidation in the liver results in abundant ___ and ___ __.
ATP
NADH
acetyl CoA
Regulation of ketone body synthesis:
Elevated levels of NADH in the liver drives the TCA cycle ___, oxaloacetate is converted to ___ which is then used in gluconeogenesis. The reduction of oxaloacetate diverts the acetyl CoA into ___ ___ ___, rather than the TCA cycle.
Backwards
Malate
Ketone body synthesis
Ketone body synthesis in the liver requires three molecules of ___ ___ which form the branched ________ ___. Removal of one acetyl CoA leaves the ketone acid ____.
Acetyl CoA
3-hydroxy-3-methylglutaryl CoA
Acetoacetate
Acetoacetate is reduced to ____ which is the most abundant ketone body. Acetoacetate can also be decarboxylated to ____ non-enzymatically, which is responsible for the characteristic fruity breath in a person in ketoacidosis.
Hydroxybutyrate
Acetone
Ketone bodies produced by the liver can be used as fuel by the ___, ___, and ___ __. They are converted back into acetyl CoA and oxidized in the ____ ___.
Brain, heart, skeletal muscle
TCA cycle
Most dietary unsaturated fats have ___ double bonds. Enoyl CoA hydratase can only accept substrates with ___ double bonds. ____ ___ ____ converts cis to trans double bonds.
Cis
Trans
Enoyl CoA isomerase
Unsaturated fatty acid additional energy requiring step, indicated by the green arrow below:
Overview of peroxisomal oxidation of very long chain fatty acids (>22 carbons):
Picture compares beta oxidation to peroxisomal oxidation
w-oxidation:
If there is a disruption in beta oxidation, fatty acids can be metabolized on the ____ ___. Cytochrome p450 enzymes can oxidize the ___ terminal carbon to a carboxyl, producing a ____ fatty acid. Both ends terminate in ____. Acetyl CoA is cleaved from both ends until the ___ are broken down to medium chain ___, these may be used by other tissues or excreted in the urine.
Endoplasmic reticulum
w
Dicarboxyl
Carboxyls
Dicarboxyls
Dicarboxyls
Branched chain fatty acids:
Breakdown of phytanic acid, first the ___ carbon is oxidized to carbon dioxide. Then beta-oxidation occurs, alternately releasing ____ CoA and ___ CoA.
Alpha
Propionyl
Acetyl
Odd chain length fatty acids:
Beta oxidation occurs normally until the chain is ___ carbons long. Then ___ makes one molecule of acetyl CoA and one Propionyl CoA
Five
Thiolase
____ cut phospholipids at different locations. Phosphatidylinositol 4-5 bisphophate is a substrate for ____ __, the products are diacylglycerol and inositol 1,4,5 trisphosphate.
Phospholipases
Phospholipase C
Triacylglycerol synthesis:
____ are the main storage form of fatty acids in the body.
Fatty acids are synthesized from ____ derived carbon in the liver and adipose cells whenever ingested calories ___ the requirement for energy.
Triacylglycerols
Carbohydrate
Exceed
The pyruvate/Malate cycle has two functions in lipogenesis:
1. Transports acetyl CoA from the ___ to the ____
2. Malic enzymes generate ____ to power fatty acid synthesis
Mitochondria
Cytosol
NADPH
When carbohydrate energy is abundant, the ___ ___ ____ is active and also contributes NADPH reducing power for fatty acid synthesis.
Pentose phosphate pathway
Fatty acid synthesis overview:
First step of fatty acid synthesis:
Cytoplasmic acetyl CoA is converted to ___ ___ by the addition of carbon dioxide. ___ ___ ____ catalyzes this reaction using biotin as a cofactor.
Malonyl CoA
Acetyl CoA carboxylase
Acetyl CoA carboxylase regulation:
The product of acetyl CoA carboxylase reaction, ___ __, allosterically inhibits Carnitine palmitoyl transferase (CPT1), which stops ___ ___ of fatty acids while fatty acid synthesis is occurring.
Malonyl CoA
Beta-oxidation
____ ___ ____ activity fine tunes the regulation of fatty acid beta oxidation. It is activated by ____ phosphorylation.
Malonyl CoA decarboxylase
AMP-K
Fatty acid synthesis sequence compared to beta-oxidation sequence:
FAS:
One sulfur atom is from a ____ side chain on another protein subunit of FAS. The other sulfur is _____ group covalently linked to a serine residue on the Acyl carrier protein subunit of FAS.
Cysteine
Phosphoantetheinyl
Fatty acid synthesis: first step is bond formation:
Two ____ units from ___ ___ are first added to the phosphopantetheinyl sulfur and then transferred to the cysteine sulfur.
Carbon
Acetyl CoA
Fatty acid synthesis: first step is bond formation:
Two carbons units from __ ___ are added after the carbons from acetyl CoA. The acetate from the cysteine carbon is transferred to the ____ and is ___.
Malonyl CoA
Malonyl
Decarboxylated
Fatty acid synthesis: second step is reduction:
The keto group is reduced to an ___. ____ oxidation powers the reaction.
Alcohol
NADPH
Fatty acid synthesis: third step is dehydration:
Water is removed and a carbon carbon ___ bond is formed.
Double
Fatty acid synthesis: fourth step is reduction:
The carbon carbon double bind is reduced. Oxidation of _____ powers the reaction.
NADPH
All three reactions of reduction, dehydration, and reduction again are catalyzed by ___ ___ ___, a multisubunit cytosolic enzyme. Two ____ are oxidized each cycle.
Fatty acid synthase
NADPH
Fatty acid synthase:
The four carbon fatty acid chain is transferred from the _____ to the ____. A new ___ ___ can bind the phosphopantetheinyl and the process of chain ____ continues for another cycle. Cycles continue until the Acyl chain is ___ carbons long- ____.
Phosphopantetheinyl
Cysteine
Malonyl CoA
Elongation
16
Palmitate
Overview of lipogenesis:
Overview of fatty acid synthesis:
___ ___ ____ generates Acetyl CoA and helps fine tune the pool of malonyl CoA, which coordinately regulates ___ ___ ___ and serves as substrate for ___ ___ ___.
Malonyl CoA decarboxylase (MCD)
Fatty acid oxidation
Fatty acid synthesis
In the fasted state, malonyl CoA decarboxylase (MCD) is ____ by AMPK. Acetyl CoA carboxylase (ACC) is ____ by AMPK.
Activated
Inactivated
In the absence of malonyl CoA decarboxylase (MCD), cells can not turn on ___ ___ ___ ___ in response to low energy conditions. Deficiency is associated with metabolic ___, ____, developmental delays, seizures, and cardiomyopathy.
Fatty acid beta oxidation
Acidosis
Hypoglycemia
