Fatty acids

oxidation and
Ketogenesis
By :Razan Shawgi
1) Lipids are stored in the body mainly in
the form of
(A) Phospholipids (B) Glycolipids
(C) Triglycerides (D) Fatty acids
2) Lipid stores are mainly present in
(A) Liver (B) Brain
(C) Muscles (D) Adipose tissue
• 3) Which of the following regulates lipolysis
in adipocytes?
• (A) Activation of fatty acid synthesis mediated by
• CAMP
• (B) Glycerol phosphorylation to prevent futile
• esterification of fatty acids
• (C) Activation o f hormone sensative lipase as a result of
hormone stimulated increases in CAMP levels
• (D) Activation of CAMP production by Insulin
 4) Glycerol is converted into glycerol-3-
• phosphate by
• (A) Thiokinase (B) Triokinase
• (C) Glycerol kinase (D) All of these
• 5) Glycerol released from adipose tissue by
• hydrolysis of triglycerides is mainly
• (A) Taken up by liver
• (B) Taken up by extrahepatic tissues
• (C) Reutilised in adipose tissue
• (D) Excreted from the body
6)Free glycerol cannot be used for triglyceride
• synthesis in
• (A) Liver (B) Kidney
• (C) Intestine (D) Adipose tissue
7). Adipose tissue lacks
• (A) Hormone-sensitive lipase
• (B) Glycerol kinase
• (C) cAMP-dependent protein kinase
• (D) Glycerol-3-phosphate dehydrogenase
• 8)In adipose tissue, glycerol-3-phosphate
• required for the synthesis of triglycerides
• comes mainly from
• (A) Hydrolysis of pre-existing triglycerides
• (B) Hydrolysis of phospholipids
• (C) Dihydroxyacetone phosphate formed in
• glycolysis
• (D) Free glycerol
9) The subcellular site of the breakdown of long-chain fatty
acids to
acetyl-CoA via β-oxidation is:
• A. The cytosol
• B. The matrix of the mitochondria
• C. The endoplasmic reticulum
• D. The mitochondrial intermembrane space
• E. The Golgi apparatus
 10) Carnitine is needed for fatty acid oxidation BECAUSE:
• A. It is a cofactor for acyl-CoA synthetase, which activates fatty acids
• for breakdown.
• B. Long-chain acyl-CoA (“activated fatty acids”) need to enter the
• mitochondrial matrix to be oxidized, but cannot cross the outer
• mitochondrial membrane. Transfer of the acyl group from CoA to
• carnitine enables translocation to occur.
• C. Acylcarnitine, formed when long-chain acyl groups are transferred
• from CoA to carnitine is the substrate for the first step in the β-
• oxidation pathway.
• D. Long-chain acyl-CoA (“activated fatty acids”) need to enter the
• mitochondrial intermembrane space to be oxidized, but cannot
• cross the inner mitochondrial membrane. Transfer of the acyl
• group from CoA to carnitine enables translocation to occur.
• E. It prevents the breakdown of long-chain fatty acyl-CoA in the
• mitochondrial intermembrane space.
• Carnitine is..
• Carnitine can be obtained from the diet, where it is found
• primarily in meat products. Carnitine can also be synthesized
from the aminoacids lysine and methionine by an enzymatic
pathway found in the liver andkidney but not in skeletal or
heart muscle
• fatty acids shorter than 12 carbons can cross the inner
mitochondrial membrane without the aid of carnitine or the
CPT system. Once inside the mitochondria, they the activated
to their CoA derivatives by matrix enzymes, and are oxidized.
• 11). Carnitine acylcarnitine translocase is
• present
• (A) In the inner mitochondrial membrane
• (B) In the mitochondrial matrix
• (C) On the outer surface of inner mitochondrial
• membrane
• (D) On the inner surface of inner mitochondrial
• membrane
• 12)A 6-month-old baby was doing well until he developed viral gastroenteritis
and was unable to tolerate oral feeding for 2 days. He is admitted to the
hospital with encephalopathy, cardiomegally and heart failure, poor muscle
tone, and hypoketotic hypoglycemia. Bloodwork did not detect any medium-
chain dicarboxylic acids.Once this baby is diagnosed and treated, his diet will
need to be very restricted. Theoretically, which one of the following fatty acids
• will he be able to consume and metabolize?
• (A) An 8-carbon fatty acid
• (B) A 14-carbon fatty acid
• (C) A 20-carbon fatty acid
• (D) Only unsaturated fatty acids, regardless of
• chain length
• (E) Only saturated fatty acids, regardless of
• chain length
• This baby has primary carnitine deficiency, an autosomal
recessive disorder. The lack of medium-chain dicarboxylic acids in
the blood rules out an MCAD deficiency.
• He is unable to transport blood-borne carnitine into the muscle and
liver, thereby blocking
• fatty acid oxidation in those tissues. Carnitine is required to
transfer most fatty acids from the
• cytoplasm to the matrix of the mitochondria. However, short- and
medium-chain fatty acids
• (up to 10 or 12 carbons) are sufficiently water-soluble such that
they can enter cells and be
• transferred into the mitochondria in the absence of carnitine
 oxidation of fatty acids
β-Oxidation of fatty acids
The major pathway for catabolism of fatty
acids is a mitochondrial pathway called β-
oxidation, in which two-carbon fragments are
successively removed from the carboxyl
end of the fatty acyl CoA, producing acetyl
CoA, NADH, and flavin adenine dinucleotide
(FADH2).
• It consists of a sequence of four reactions involving the β-carbon (carbon 3) that
• results in shortening the fatty acid chain by two carbons at the carboxylate end.
The
• steps include an oxidation that produces FADH2, a hydration step, a second
• oxidation that produces NADH, and a thiolytic cleavage that releases a molecule
of
• acetyl CoA. Each step is catalyzed by enzymes with chain-length specificity. These
• four steps are repeated for saturated fatty acids of even-numbered carbon chains
• (n/2) - 1 times (where n is the number of carbons), each cycle producing one acetyl
• CoA plus one NADH and one FADH2. The acetyl CoA can be oxidized or used in
• hepatic ketogenesis
• Very long chain FA oxidation occur in....
• 15) All the following can be oxidized by β-
• oxidation except
• (A) Palmitic acid
• (B) Phytanic acid
• (C) Linoleic acid
• (D) Fatty acids having an odd number of carbon
• atoms
 α-oxidation of FA
• Removal of one C atom at a time from the carboxyl end.
• The presence of alkyl group (CH3, CH2) on β carbon prevents β oxidation.
• Does not require CoA intermediates.
• Does not generate high energy phosphate
• Clinical aspects
• Refsum’s disease ↑ Phytanic acid ↓ α oxidation
• Hyopglycin inactivates medium & short chain acyl-CoA dehydrogenase.
• Dicarboxylic aciduria lack of mitochondrial medium chain acyl CoA
dehydrogenase (MCAD): ↑ ω oxidation.
• Zellweger’s syndrome absent peroxisomes
• Hypoglycaemic sulphonylureas ↓FA oxidation (CPT).
• Clofibrates (hypolipidimic drug that lower triacylglycerol) ↑peroxisomal
β.oxidat
16)Propionyl CoA is formed on oxidation of
• (A) Monounsaturated fatty acids
• (B) Polyunsaturated fatty acids
• (C) Fatty acids with odd number of carbon atoms
• (D) None of these
17)Which of the following products of
• triacylglycerol breakdown and subsequent
• β-Oxidation may undergo gluconeogenesis?
• (A) Acetyl CoA (B) Porpionyl CoA
• (C) All ketone bodies (D) Some amino acids
•  
• 18) Long chain fatty acids are first activated
to acyl CoA in the
• (A) Cytosol (B) Mitochodria
• (C) Ribosomes (D) Microsome
19)In β−oxidation of fatty acids which of the
• following are utilized as co-enzymes?
• (A) NAD+ and NADP+
• (B) FAD H2 and NADH + H+
• (C) FAD and FMN
• (D) FAD and NAD+
•  
20)β-Oxidation of fatty acids requires all the
• following coenzymes except
• (A) CoA (B) FAD
• (C) NAD (D) NADP
21)During each cycle of β-oxidation
• (A) One carbon atom is removed from the
• carboxyl end of the fatty acid
• (B) One carbon atom is removed from the methyl
• end of the fatty acid
• (C) Two carbon atoms are removed from the
• carboxyl end of the fatty acid
• (D) Two carbon atoms are removed from the
• methyl end of the fatty acid
22)The breakdown of one molecule of a C16 fully saturated
fatty acid(palmitic acid) by β-oxidation lead to the formation of:
• A. 8 FADH2, 8 NADH, and 8 acetyl-CoA molecules
• B. 7 FADH2, 7 NADH, and 7 acetyl-CoA molecules
• C. 8 FADH2, 8 NADH, and 7 acetyl-CoA molecules
• D. 7 FADH2, 8 NADH, and 8 acetyl-CoA molecules
• E. 7 FADH2, 7 NADH, and 8 acetyl-CoA molecules
• Discuss‫؛‬
• Net energy yelid by comple oxidation of 1 mol of Palmitic
acid....
• 23). Malonyl-CoA, the first intermediate in fatty acid synthesis, is an important
regulator of fatty acid metabolism BECAUSE:
• A. Its formation from acetyl-CoA and bicarbonate by the enzyme
• acetyl-CoA carboxylase is the main rate-limiting step in fatty acid
• synthesis.
• B. It prevents entry of fatty acyl groups into the matrix of the
• mitochondria because it is a potent inhibitor of carnitine palmitoyl
• transferase-I.
• C. It prevents entry of fatty acyl groups into the matrix of the
• mitochondria because it is a potent inhibitor of carnitine palmitoyl
• transferase-II.
• D. It prevents entry of fatty acyl groups into the matrix of the
• mitochondria because it is a potent inhibitor of carnitine–
• acylcarnitine translocase.
• E. It inhibits the synthesis of fatty acyl-CoA.
24)All the following statements regarding
• ketone bodies are true except
• (A) They may result from starvation
• (B) They are formed in kidneys
• (C) They include acetoacetic acid and acetone
• (D) They may be excreted in urine
 
25)Ketone bodies are synthesized in
• (A) Adipose tissue (B) Liver
• (C) Muscles (D) Brain
26)An enzyme required for the synthesis of
• ketone bodies as well as cholesterol is
• (A) Acetyl CoA carboxylase
• (B) HMG CoA synthetase
• (C) HMG CoA reductase
• (D) HMG CoA lyase
27) After they are produced from acetyl-CoA in the liver,
ketone bodies
• are mainly used for which one of the following processes?
• A. Excretion as waste products
• B. Energy generation in the liver
• C. Conversion to fatty acids for storage of energy
• D. Generation of energy in the tissues
• E. Generation of energy in red blood cells
•  
• 28)A 14-year-old girl with Type 1 diabetes has had
• viral gastroenteritis for 5 days, and she has been
• vomiting, been nauseous, and had trouble taking
• fluids by mouth. Because she was not eating, she
• did not take any insulin during her illness. She becomes weak and confused and is taken to the
• emergency room (ER) by her parents. The ER doctor notices a fruity odor to her breath,
hyperventilation, and a blood glucose level of 600 mg/dL
• The patient is hyperventilating because of
• which one of the following?
• (A) The low pH of the blood
• (B) The elevated pH of the blood
• (C) The increased glucagon/insulin ratio in
• the blood
• (D) Lack of fluids in the body
• (E) Difficulty in breathing due to the lack of food
• 29)The fruity odor noticed by the ER physician is due to which one of the following?
• (A) Oxidation of acetoacetate
• (B) Reduction of acetoacetate
• (C) Conversion of acetoacetate to
• acetoacetyl-CoA
• (D) Decarboxylation of acetoacetate
• (E) Carboxylation of acetoacetate
• 30) Type 1 diabetes mellitus is caused by a
• decreased ability of the
• β cells of the pancreas to
• produce insulin. A person with Type 1 diabetes
• mellitus who has neglected to take insulin injections will exhibit which one of the
following?
• (A) Increased fatty acid synthesis from glucose
• in liver
• (B) Decreased conversion of fatty acids to
• ketone bodies
• (C) Increased stores of triacylglycerol in
• adipose tissue
• (D) Increased production of acetone
• (E) Increased glucose transport into
• muscle cel