Exam 2

Question 1

Galactokinase Deficiency

Answer 1

Elevated Galactose in the blood (galactosemia)and urine (galactosuria). Elevated galactisol = cataracts. Treatment is dietary restriction

Question 2

Galactose 1 Phosphate uridylytransferase deficiency

Answer 2

Symptoms - Galactosemia, Galactosuria, vomiting and diarrhea
Effects- Liver damage , intellectual disability, cataracts
Treatment - Remove galactose from diet

Question 3

Galactose Metabolism

Answer 3

From lactose in milk, digested by lactase in intestinal brush-borders.
*Lactose Intolerance from lactase deficiency causes diarrhea, bloating and
abdominal cramps following milk ingestion.
*Galactosemias are autosomal recessive diseases due to a defect in the gene
encoding galactokinase or galactose 1-uridyltransferase (classic galactosemia –
more severe).
*Patients have elevated levels of plasma galactose.
*Signs and symptoms of Classical Galactosemia include lethargy, vomiting after
ingesting lactose, hypotonia, mental retardation, cataracts and failure to thrive.
They are prone to bacterial infections eg
E.coli
*Jaundice (hyperbilirubinemia) results from the accumulated galactose 1-
phosphate which inhibits phosphoglucomutase (converts glucose 1-phosphate to
glucose 6-phosphate). This inhibits recycling of UDP-glucose that is used for
UDP-glucuronate synthesis - UDP-glucuronate is used for bilirubin conjugation.
*Treatment involves a galactose free diet.
*In well fed states glucose 1-phosphate is
channeled into glycogenesis.
*In hypoglycemia, galactose administration
can increase blood glucose levels.
*Galactose accumulation in the blood can lead
to its conversion to galactitol in the lens by
aldolase reductase causing osmotic swelling
and cataract formation in the lens and nerve
damage.

Question 4

This is why
diabetics are
at risk.

Answer 4

These pathways occur in the
lens, kidneys and Schwann
cells. They lack sorbitol
dehydrogenase which
results in cataracts,
retinopathy and peripheral
neuropathy

Question 5

Fructose Metabolism

Answer 5

From fruits, honey, sucrose(table sugar),corn syrup and
sorbitol. Most tissues phosphorylate fructose through
hexokinase slowly but the liver and kidneys use
fructokinase.
*Because the DHAP and glyceraldehyde 3-phosphate are
downstream from the key regulatory step in glycolysis
(PFK1), fructose is a quick source of energy and can also be
readily used for triglyceride biosynthesis.

Question 6

Fructokinase deficiency (Essential Fructosuria)

Answer 6

mild disorder, Benign conditin, Auto Somal recessive , fructose not trapped in cells, no cataract (ketone) fructosuria. is an
autosomal recessive disorder with a mild phenotype
because fructose is not trapped within cells, there is no
cataract because fructose is a ketose not an aldose.

Question 7

Aldolase B deficiency

Answer 7

Fructose 1 accumulation = depletion of ATP
Inhibits production of dihydroxyacetone and glyceraldehyde to produce pyruvate = no glucose made
Symptoms : hypoglycemia , vomiting, jaundice , hemorrhage, hepatomegaly , renal dysfunction , hyperuricemia

Question 8

Primary Purposes for Pentose Phosphate Pathway

Answer 8

Biosynthetic:
NADPH
Ribose 5-phosphate and others

Protective:
NADPH
* Metabolism of
xenobiotics
* Removal of reactive
oxygen

Can operate in several different
modes depending on cellular
conditions

Two branches: Oxidative and non-
oxidative

Question 9

Pentose Phosphate Pathway key facts

Answer 9

NADH - has a phosphate group to allow certain molecule to bind like nucleotides

An alternate pathway of glucose metabolism

Occurs in the cytoplasm of all cells especially
lactating mammary glands, liver, adrenal cortex
and RBCs

Does not yield ATP

It leads to the formation of NADPH for fatty acid
biosynthesis and maintaining reduced glutathione
for antioxidant activity

It also leads to the formation of ribose sugars for
nucleic acid synthesis.

Question 10

Pentose Phosphate Pathway main functions

Answer 10

Generate NADPH
Pentose Sugar Ribose

Question 11

Pentose Phosphate Pathway happens when

Answer 11

NADPH is low
Insulin triggered

Question 12

Oxidative

Answer 12

Stops at Ribose 5 Phosphate
Produced 2 NADPH
DNA formation

Question 13

Non Oxidative

Answer 13

Bring metabolites back into glycolysis to gluconeogenesis pathway to form intermediates

Question 14

Pentose Pathway Location

Answer 14

Cytoplasm of all cells especially lactating mammary glands , liver adrenal cortex and RBC

Question 15

Key Steps in the pathway

Answer 15

The rate-limiting step is catalyzed by Glucose 6-phosphate
dehydrogenase(G6PD)
It involves an irreversible oxidative phase involving G6PD and 6-
phosphogluconate dehydrogenase with the production of ribulose 5-
phosphate and the production of NADPH.
G6PD is induced by insulin and inhibited by NADPH and activated by NADP
This is followed by the reversible oxidative phase beginning with ribulose 5-
phosphate producing an equilibrated pool of sugars used in biosynthetic
reactions
Fructose 6-phosphate and glyceraldehyde 3-phosphate are intermediates
of this pathway and can be channeled into glycolysis directly.
Transketolase is important for these interconversions and is thiamine-
dependent. It is the only thiamine dependent enzyme in erythrocytes.
(can be used to evaluate a patient’s nutrituional status for thiamine

Question 16

USES OF
NADPH

Answer 16

1. Relax smooth muscles
2. Prevent platelet aggregation
3. Acts as a neurotransmitter in
   brain
4. Mediates tumoricidal and
   bactericidal actions of
   macrophages

Question 17

G6PD Deficiency

Answer 17

X-linked recessive disease, common in areas where malaria is
endemic.
Peroxides generated in RBCs are destroyed by glutathione
peroxidase/reductase system (which uses NADPH. Other cells
that produce NADPH by using alternate enzymes like malate
dehydrogenase are not susceptible to this oxidative damage
like RBCs are.
Patients have episodic acute hemolysis because of
accumulated ROS, protein denaturation and lipid peroxidation
– membrane fragility.
Fava beans(favism), Infections, moth balls (naphthalene) and
some drugs(primaquine, dapsone, isoniazid) predispose to
hemolysis in these patients – strong oxidizing agents!

Question 18

Carbohydrate
Catabolism

Answer 18

Key Point:
* The citric acid cycle IS the Engine that drives energy
production regardless of the source:
* Carbohydrate -> acetyl CoA
* Lipid -> acetyl CoA
* Protein -> acetyl CoA
* Certain nucleotides -> acetyl CoA

Question 19

How does NADH
get into the
mitochondria?

Answer 19

Very polar: ie cannot diffuse
through the mitochondrial
membrane.

• NADH doesn’t actually cross the
  membrane: The electrons are
  moved across the membrane:

Question 20

Organ specific transport
mechanisms:

Answer 20

Heart and Liver use a common transport
mechanism
* Brain and skeletal muscle use a different
mechanism

Question 21

Transport of NADH into the mitochondria

Answer 21

TCA occurs in the mitochondria: NADH is already inside
Glycolysis occurs in cytosol: NADH must be
transported

Question 22

Complex I

Answer 22

NADH + Q-> NAD+
+ QH2
* Electrons enter from the matrix
* H+ ions are “pumped” out of the mitochondria in
response to the electrons moving through the
complex from NADH to Q
* This transfer is highly favorable
* One arm extends
into the matrix
* The other is fully
membrane
bound
* CoQ: Eo’ = 0.045

Question 23

Complex II

Answer 23

Succinate + Q -> Fumarate
+ QH2

Complex II
* Not a pump, so no contribution to the membrane
potential or ATP formation
* Like complex I, electrons are delivered to Q
* Both Complex I and II contribute to the pool of QH2
in the mitochondrial membrane

Question 24

Complex III

Answer 24

QH2 + 2Cytc(ox) -> Q + 2H+ + 2Cytc(red)
DEo’ = 0.19 V
DGo’ = -36.6 KJ/mol
contains high and low potential heme cofactors

• Stoichiometry changes: 1 QH2 reduces 2
  cytochrome c
• Cytochrome c is a peripheral membrane protein
  that migrates along the out surface of the inner
  mitochondrial membrane.
  Complex III is also a “pump” that moves H+ ions
  across the membrane from inside to outside and
  helps to generate the membrane potential.

Question 25

Complex IV

Answer 25

4 Cytcred + O2 + 4 H+--> 4 Cytcox + 2 H2O * Electrons finally reach their ultimate home. * Lowest energy state for the electrons is on oxygen in the form of water. * The movement of these electrons to their lowest energy state is coupled to the generation of a membrane potential (a charged battery) * The mitochondrial membrane is now ready to produce ATP by allowing a H+ “current” to pass through.

Question 26

How does electron flow drive H+ translocation and what is it’s significance?

Answer 26

Energy is stored in the proton gradient!

Question 27

ATP Synthase: Features

Answer 27

Lolipop structure F1 subunit extends into the matrix of the mitochondria This is where ATP is synthesized F0 unit is membrane bound

Question 28

Molecular Motion in ATPase

Answer 28

A look down the 3-fold axis of the F1 ATPase. Channel is lined with hydrophobic amino acids. Perfect for slippery surface for rotation

Question 29

Why is rotation important?

Answer 29

Binding change mechanism ATP release is key to catalysis In T-state, ATP synthesis occurs spontaneously

Question 30

Transport of Material

Answer 30

ATP has -4 charge ADP has -3 charge

Question 31

Proposed Rotary Action

Answer 31

Protons want to move from bottom to top. Only way to move is through rotation of the c ring with respect to the alpha3beta3

Question 32

Uncoupling: A source of Heat

Answer 32

Hibernating animals can generate heat this way. “Brown Fat” Honey bees and futile cycles

Question 33

HYPOPHOSPHATEMIA AND GLYCOLYSIS

Answer 33

May be caused by parenteral nutrition, malnourishment(refeeding syndrome), chronic alcohol abuse, diabetic ketoacidosis, sepsis, respiratory alkalosis, or primary hyperparathyroidism, Fructosemia and galactosemia In glycolysis, it inhibits; Glyceraldehyde 3-phosphate dehydrogenase Impairs mitochondrial ATP synthesis Diminishes 2,3BPG levels and impairs tissue oxygenation Increased hemolysis and impaired leukocyte function (sepsis)

Question 34

Nucleotide Kinase

Answer 34

: Forms UTP from UDP

Question 35

Myokinase

Answer 35

Creates ATP from 2 ADP: Also form AMP which is a key regulator , and also involved in the AMP cycle to boost TCA activity

Question 36

Creatine phosphate

Answer 36

High energy phosphate “buffer” in muscle cells to regenerate ATP immediately after exercise begins.

Question 37

Insulin Secretion

Answer 37

Insulin secretion in beta cells is triggered by rising blood glucose levels. Glucose uptake by the GLUT2 transporter leading to cell depolarization, calcium influx leading to the exocytotic release of insulin from their storage granule.

Question 38

3-Steps in Glycogen breakdown

Answer 38

I. release of glucose 1-phosphate by the phosphorylase (PLP-dependent) Vitamin B6 II. phosphoglucomutase III. debranching (transglycosylase and hydrolysis).

Question 39

Glycogen Breakdown

Answer 39

Glycogen Phosphorylase Pyridoxal phosphate (B6) dependent Phosphorolysis (ie like hydrolysis) Energy conservation in the phosphate linkage. Produces glucose 1-phosphate

Question 40

Key enzyme in regulating breakdown is glycogen phosphorylase

Answer 40

Hormonal: Insulin and glucagon AMP activation G1P and G6P inhibition Regulation is tightly coordinated with the activity of the Glycogen Synthase, which regulates synthesis.

Question 41

Glycogen Synthesis

Answer 41

Different mechanism for synthesis than for breakdown. This was realized when the cause of McArdle’s disease was discovered. Defective phosphorylase Energy requirement: UTP used as an energy source DG under physiological conditions is +5 to +8 KJ/mol. Introduction to “energy coupling”

Question 42

Three activities required for synthesis from G1P

Answer 42

I. UDP-Glucose Pyrophosphorylase II. Synthase III. Branching enzyme

Question 43

UDP-glucose Pyrophosphorylase

Answer 43

Release of pyrophosphate for subsequent hydrolysis provides additional thermodynamic driving force.

Question 44

Branching Enzyme

Answer 44

7 residue fragment is transferred from one branch to start another Transferred branch must come from a chain of at least 11

Question 45

Regulation of Glycogen metabolism

Answer 45

Synthesis and breakdown are both spontaneous under normal cellular conditions. (Just like glycolysis and gluconeogenesis) Requires tight regulation Phosphorylase and Synthase are inversely regulated by the same cellular signal

Question 46

Hormonal regulation of Liver phosphorylase:

Answer 46

Key hormones: glucagon, epinephrine, Insulin

Question 47

Diabetes Melitus : Type I

Answer 47

: Autoimune disease resulting from destruction of pancreatic b-cells responsible for insulin production. Sometimes called insulin sensitive, because administration of insulin will restore blood glucose level.

Question 48

Diabetes Melitus : Type II

Answer 48

Adult onset: results from a continuing desensitization of cells toward insulin. Cannot be treated with insulin.

Question 49

Diabetes Melitus

Answer 49

Both cause hyperglycemic episodes, which can damage blood vessels and create a host of other medical conditions (glaucoma).

Question 50

underlying causes of diabetes melitus

Answer 50

Glut 1 moves glucose across to fetus A hyperglycemic mother will lead to hyperglycemic fetus Endocrine system of the fetus controls how the glucose is utilized Normal fetus has anabolic conditions (synthesis and storage) Hyperglycemic fetus produces more insulin Glut 4 is produced in late gestational stage in muscle and fat. This explains the large size of infants of diabetic mothers

Question 51

Normal transitioning after child-birth

Answer 51

At birth: Glucose supply is cut off Approximately 7 min worth of glucose Initial depletion of glucose results in mobilization of liver glycogen This results from hormonal changes Beyond 12 hours, gluconeogenesis is the primary source of glucose from amino acids that are glucogenic Fatty acids also provide energy to compensate as glucose falls: glucagon stimulate lipolysis and release of fatty acids Brain will switch to ketone bodies, heart turns to fatty acid

Question 52

Diabetic Problem

Answer 52

Endocrine environment of the newborn from diabetic mother is poised to remove glucose: Very high insulin: Double that of normal infant.

Question 53

Effects of Insulin: Summary

Answer 53

Inhibits ketogenesis Inhibits lipolysis Inhibits gluconeogenesis Inhibits glycogen breakdown Stimulates lipid synthesis Stimulates glycogen synthesis Stimulate glycolysis

Question 54

Pyruvate Carboxylase Deficiency

Answer 54

Symptoms range from benign to severe and include fasting hypoglycemia, hypothermia, hypotonia, neurologic dysfunction, vomiting, lactic/ketoacidosis. Pyruvate carboxylase catalyzes the formation of oxaloacetate from pyruvate and CO2 in the mitochondrial matrix. It’s biochemical significance involves gluconeogenesis, anaplerosis and lipogenesis. It is exported by the malate aspartate shuttle into the cytoplasm for conversion to phosphoenolpyruvate unto glucose Oxaloacetate is used for the generation of intermediates for the TCA cycle Aspartate is formed by transamination of oxaloacetate in the mitochondrial matrix but in PC deficiency, aspartate levels will be low – impaired gluconeogenesis and electron transfer for ATP generation. An impaired electron transfer lowers the redox equilibrium in the mitochondrial matrix lowers the β-hydroxybutyrate/acetoacetate ratio - ketoacidosis The cytoplasmic redox equilibrium promotes the formation of lactate from pyruvate leading to lactic acidosis and reducing the supply of acetyl-CoA to the TCA cycle. Low aspartate levels lead to hypercitrullinemia, hyperammonemia and low plasma glutamate levels. PC deficiency impairs lipogenesis due to the depletion of pyruvate, oxaloacetate and acetyl-CoA required for fatty acid biosynthesis – widespread demyelination of cerebral and cerebellar white matter characteristic of the disease.

Question 55

Alcohol and Hypoglycemia

Answer 55

In addition to poor nutrition, alcohol metabolism to acetyl-CoA generates a lot of NADH in the cytoplasm NADH favors the formation of lactate from pyruvate, malate from OAA and glycerol 3-phosphate from DHAP The large amounts of NADH inhibit gluconeogenesis and favor lipid accumulation in the liver and excessive storage of triglycerides(alcoholic steatosis). They also delay fatty acid oxidation So with exercise and accumulation of lactate, NAD+ is not available for conversion of lactate to pyruvate because it is used to metabolize alcohol. All these promote hypoglycemia!

Question 56

Lingual lipases

Answer 56

Act on TAGS in the saliva and into the stomach.

Question 57

Gastric Lipases

Answer 57

small amounts active at low pH

Question 58

enterogastrone hormones secreted by the duodenal mucosa:

Answer 58

inhibits HCl production and forward movement of gastric contents (ie, slows gastric emptying) allowing the churning action of the stomach

Question 59

Intestinal lipases

Answer 59

Small intestines Steapsin (a lipase) and cholic acids (other bile salts) Secreted by Pancreatic and Bile ducts

Question 60

Uptake and /or storage of fats

Answer 60

In adipose tissue, liver, muscle etc…. Lipoprotein Lipases in the blood vessel walls release FAs and glycerol (attached to vessel walls by Heparin-sulfate) Apolipo CII binds LPL, which activates the lipoprotein lipases on vessel walls FAs are taken up by the tissue. Glycerol is generated from glucose and TAGs are synthesized

Question 61

Steps in Fatty acid Metabolism

Answer 61

Hormone sensitive lipases release Free Fatty acids from adipose tissue Free fatty acids travel in the blood associated with plasma proteins (Albumin) Uptake by peripheral tissue is passive, thus dependent on concentration Free diffusion Fatty acid transport proteins

Question 62

Breakdown of fatty acids for fuel.

Answer 62

FAs are transported via a FA transport protein (along with Na+ into the cell). FAs are taken up in the cell and transported (chauffeured) by FA binding proteins. They are activated via attachment to CoA-SH Transported inside the mitochondria via Carnitine transporter and acyl transferase system b-oxidation cycle generates acetyl-CoA: No need to know a- or w-oxidation

Question 63

Fat metabolism includes the following processes

Answer 63

1. Digestion, absorption, and transport of dietary fat 2. Generation of metabolic energy from this fat 3. Storage of excess fat in adipose tissue 4. Significant Metabolic links between triglycerides and other biomolecules, including carbohydrates and ketone bodies

Question 64

FATTY ACIDS: Structure review

Answer 64

Fatty acids are long-chain carboxylic acids (R-COOH) The carboxyl carbon is number 1 and carbon number 2 is the α carbon. When naming fatty acids, the number of carbon atoms and double bonds are used together eg palmitic acid (C16:0), Linoleic acid (C18:2) Saturated fatty acids do not have double bonds while unsaturated fatty acids have double bonds. Saturated fatty acids in plasma membranes restrict membrane fluidity unlike unsaturated fatty acids

Question 65

Defects related to FA metabolism

Answer 65

Systemic Carnitine Deficiency Zellweger’s syndrome (spectrum Disorder) X-linked adrenoleukodytrophy C-P transferase deficiency (Type I and II) Jamaican Vomiting Sickness: (ACDH) Hypoglycin A SIDS (MCACDH)

Question 66

Fatty acid – glucose relationship

Answer 66

Glucose can be converted to Fatty Acids via production of acetyl CoA through Glycolysis and PDH Fatty Acids cannot be converted to glucose because the PDH reaction is irreversible and there is no other metabolic route in humans. Exception: Odd chain Fatty acids: BECAUSE

Question 67

Synthesis of fatty acids from Acetyl CoA

Answer 67

Occurs in the cytosol mitochondrial conditions influence synthesis

Question 68

Fatty Acid Regulation

Answer 68

NADH, ATP: internal Insulin: external High ATP -> low ETC -> High NADH -> Low TCA -> High Citrate

Question 69

Citrate shuttle and Malic enzyme

Answer 69

The citrate shuttle transports acetyl-CoA groups (as citrate) from the mitochondria to cytoplasm for fatty acid synthesis. This is promoted by high NADH, ATP and insulin. In the cytoplasm, ATP-citrate lyase splits citrate into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondria: malic enzyme supports this by converting malate into pyruvate This generates NADPH supplementing HMP shunt (PPP). Acetyl-CoA carboxylase activates acetyl-CoA and catalyzes the rate-limiting step in fatty acid biosynthesis. It requires biotin, ATP and CO2. Its controls include insulin and citrate activation. The CO2 in not incorporated into the fatty acid but removed by the subsequent step (fatty acid synthase)

Question 70

Acetyl-CoA Carboxylase

Answer 70

Acetyl-CoA Carboxylase catalyzes the rate-limiting step in FA synthesis Sources of acetyl-CoA include pyruvate, isoleucine, lysine, leucine, tryptophan (? High protein diet) It uses biotin as a co-factor.  The ATP-dependent carboxylation of the biotin is followed by a transfer of the carboxyl group to acetyl-CoA to form malonyl-CoA. It is induced by insulin (dephosphorylation), citrate and ATP but inhibited by Palmitoy-CoA, AMP, glucagon and epinephrine The summary is: HCO3- + ATP + acetyl-CoA  ADP + Pi + malonyl-CoA

Question 71

METFORMIN

Answer 71

Oral hypoglycemic agent used in Insulin-independent diabetes mellitus and insulin-resistance (Polycystic Ovarian Syndrome) Reduces blood glucose levels and promotes weight loss Inhibits Complex I of the ETC leading to increased AMP/ATP ratio Increased AMP inhibits F1,6 bisphosphatase and activates PFK-1 AMP activates AMPK which increases GLUT4 expression, It also inhibits triglyceride synthesis and lipolysis

Question 72

Acetyl-CoA Carboxylase:

Answer 72

Acetyl-CoA Carboxylase catalyzes the rate-limiting step in FA synthesis Sources of acetyl-CoA include pyruvate, isoleucine, lysine, leucine, tryptophan (? High protein diet) It uses biotin as a co-factor.  The ATP-dependent carboxylation of the biotin is followed by a transfer of the carboxyl group to acetyl-CoA to form malonyl-CoA. It is induced by insulin (dephosphorylation), citrate and ATP but inhibited by Palmitoy-CoA, AMP, glucagon and epinephrine The summary is: HCO3- + ATP + acetyl-CoA -> ADP + Pi + malonyl-CoA

Question 73

Fatty acid Synthase (FAS)

Answer 73

Also called palmitate synthase because palmitate is the first fatty acid synthesized de novo in humans. It contains an acyl carrier protein(ACP) that requires pantothenic acid. It has 2 sulfhydryl groups at Pantothenate and cysteine Malonyl-CoA is the substrate/primer for FAS, but only the carbon from acetyl-CoA is incorporated into the fatty acid. Acetyl-CoA is used as a primer then malonyl-CoA is used to add subsequent C2 to form even-numbered fatty acids while propionyl-CoA is used to form odd-chain fatty acids(in ruminant fats and milk) NADPH is the electron donor and is used to reduce the acetyl groups added to fatty acid (from PPP and malic enzyme) Eight acetyl-CoA groups are required to produce palmitate(16:0) (7 converted to Malonyl and 1 acetyl) The sequence of elongation reactions is repeated until a saturated 16-carbon acyl CoA has been assembled. Finally: When the fatty acid is 16 carbon atoms long, a Thioesterase domain catalyzes hydrolysis of the thioester linking the fatty acid to phosphopantetheine. The 16C saturated fatty acid palmitate is the final product of the Fatty Acid Synthase complex.

Question 74

fatty acid summary

Answer 74

The equation for synthesis of palmitate from acetyl-CoA, listing net inputs and outputs: 8 acetyl-CoA + 14 NADPH + 7 ATP  palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi Summary based on malonate as an input: acetyl-CoA + 7 malonyl-CoA + 14 NADPH  palmitate + 7 CO2 + 14 NADP+ + 8 CoA Fatty acid synthesis occurs in the cytosol. Acetyl-CoA generated in mitochondria is transported to the cytosol via a shuttle mechanism involving citrate.

Question 75

Elongation beyond the 16-C length of the palmitate product of Fatty Acid Synthase is mainly catalyzed by enzymes associated with the

Answer 75

endoplasmic reticulum (ER). ER enzymes lengthen fatty acids produced by Fatty Acyl Synthase as well as dietary polyunsaturated fatty acids.

Question 76

Fatty acids esterified to

Answer 76

coenzyme A serve as substrates.

Question 77

is the donor of 2-carbon units in a reaction sequence similar to that of Fatty Acid Synthase except that individual steps are catalyzed by separate proteins.

Answer 77

Malonyl-CoA

Question 78

introduce double bonds at specific positions in a fatty acid chain.

Answer 78

Desaturases

Question 79

Mammalian cells

Answer 79

are unable to produce double bonds at certain locations, e.g., ∆12

Question 80

some polyunsaturated fatty acids are dietary essentials, e.g.,

Answer 80

linoleic acid, 18:2 cis ∆9,12 (18 C atoms long, with cis double bonds at carbons 9-10 & 12-13).

Question 81

Formation of a double bond in a fatty acid involves the following endoplasmic reticulum membrane proteins in mammalian cells:

Answer 81

NADH-cyt b5 Reductase, a flavoprotein with FAD as prosthetic group. Cytochrome b5, which may be a separate protein or a domain at one end of the desaturase. Desaturase, with an active site that contains two iron atoms complexed by histidine residues.

Question 82

The desaturase catalyzes a mixed function oxidation reaction.

Answer 82

There is a 4-electron reduction of O2  2 H2O as a fatty acid is oxidized to form a double bond. 2e- pass from NADH to the desaturase via the FAD-containing reductase & cytochrome b5, the order of electron transfer being: NADH  FAD  cyt b5  desaturase 2e- are extracted from the fatty acid as the double bond is formed. E.g., the overall reaction for desaturation of stearate (18:0) to form oleate (18:1 cis D9) is: stearate + NADH + H+ + O2  oleate + NAD+ + 2H2O