Tuesday, 31 January 2017

Adaptations to dry habitats


Plants in different habitats are adapted to cope with different problems of water availability.
Mesophytes      plants adapted to a habitat with adequate water
Xerophytes        plants adapted to a dry habitat
Halophytes        plants adapted to a salty habitat
Hydrophytes      plants adapted to a freshwater habitat
Some adaptations of xerophytes are:
How it works
thick cuticle
stops uncontrolled evaporation through leaf cells
most dicots
small leaf surface area
less area for evaporation
conifer needles, cactus spines
low stomata density
fewer gaps in leaves

stomata on lower surface of leaf only
more humid air on lower surface, so less evaporation
most dicots
shedding leaves in dry/cold season
reduce water loss at certain times of year
deciduous plants
sunken stomata
maintains humid air around stomata
marram grass, pine
stomatal hairs
maintains humid air around stomata
marram grass, couch grass
folded leaves
maintains humid air around stomata
marram grass,

succulent leaves and stem

stores water
extensive roots
maximise water uptake

Describe the process of digestion of food from the mouth to the stomach The mouth

Define the following terms
 Ingestion: taking food into a living organism
 Digestion: Breaking down large insoluble food molecules into small soluble ones
 Absorption: The process by which food molecules enter the blood stream
 Assimilation: Making use of the absorbed food substances
 Egesting: Getting rid of undigested materials.

Describe the process of digestion of food from the mouth to the stomach
The mouth
Food is ingested and chewed. The teeth help to tear and grind the food into small pieces. This increases the surface area for the action of enzymes. The food is mixed with saliva which has two functions.
1. The saliva contains mucus which is a slimy substance which helps the food to be swallowed.
2. It contains the enzyme amylase which begins the digestion of starch into the sugar maltose. As food does not remain in the mouth for very long, only a small amount of starch is digested here. The food is then turned to a bollus shape by the action of the mouth and then swallowed.
This tube pushes the food to the stomach by way of rhythmic contractions. There are two sets of muscles in the oesophagus.
1. Circular muscles - these make the oesophagus narrower.
2. Longitudinal muscles - these make the oesophagus wider.
This is the way food is move all way along the alimentary canal. It is called peristalsis. The moment the food is swallowed the epiglottis closes so food isnt swallowed in the trachea.
When the food reaches the stomach gastric juice is released from the stomach lining. Gastric juice contains two substances.
1. Pepsin - an enzyme which breaks proteins down into polypeptides.
2. Hydrochloric acid - needed to activate pepsinogen to pepsin.also kills any ingested bacteria.

Nucleotide Metabolism

Roles of nucleotides in the cell:
1) Activated precursors of DNA and RNA
2) Nucleotide derivatives are activated intermediates in many biosynthetic pathways
e.g. UDP-glucose, CDP-diacylglycerol
3) Universal currency of cell (i.e. ATP)
4) Components of three major coenzymes: NAD
, FAD, and CoA
5) Metabolic regulators (i.e. cyclic AMP)
Nucleotide synthesis can either by de novo or by recycling preformed bases (salvage pathway).
Nucleotides are composed of three components:
1) nitrogenous base - pyrimidine (cytosine, uracil, thymine) or purine (adenine or guanine)
2) pentose sugar - ribose (RNA) or deoxyribose (DNA)
3) phosphate group
nucleoside - purine or pyrimidine base linked to pentose sugar
nucleotide - phosphate ester of nucleoside
Purine ring is synthesized de novo from 5 different precursors: aspartate (N-1 atom), CO2
(C-6 atom), glycine (C-4, C-5, N-7 atoms), tetrahydrofolate (C-2, C-8 atoms) and glutamine (
N-3, N-9).
Purine ring structure is synthesized from ribose 5-phosphate; PRPP then donates ribose 5-
phosphate for purine synthesis.
Purine ring is built onto the ribose 5-phosphate via a 10 -tep pathway: glutamine, glycine,
tetrahydrofolate, and glutamine make contributions to form 5-membered ring; construction
of 6-membered ring forms inosine 5’-monophosphate (IMP).
IMP can be converted into AMP or GMP
For AMP synthesis, aspartate amino group condenses with keto-group of IMP; GTPdependent
For GMP synthesis, C-2 is oxidized to form xanthosine monophosphate (XMP)
Amide nitrogen of glutamine replaces oxygen of C-2 to form GMP
ATP-dependent reaction
Synthesis of purine bases using the salvage pathway:
Free purine bases are formed by degradation of nucleic acids and nucleotides.
Purine nucleotides can be synthesized from preformed bases by salvage reactions (simpler
and less costly than de novo pathway).
Ribose phosphate portion of PRPP is transferred to purine to form the corresponding
purine PPi
PRPP purine nucleotide
Two salvage enzymes recover purine bases:
1) adenine phosphoribosyl transferase
adenine + PRPP --------> adenylate + PPi
2) hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)
hypoxanthine + PRPP --------> inosinate + PPi
guanine + PRPP ---------> guanylate + PPi
Regulation of purine nucleotide synthesis:
Probably largely by feedback inhibition.
Glutamine-PRPP amidotransferase (in main pathway) is allosterically inhbited by IMP, AMP, GMP.
Those steps leading specifically to AMP or GMP synthesis work primarily by feedback inhibition
XMP and GMP inhibit IMP dehydrogenase
AMP inhibits adenylosuccinate synthetase
Pyrimidine ring is assembled first, then linked to ribose phosphate ---> pyrimidine
Requires fewer ATPs than purine synthesis ( 2 vs. 4).
Pyrimidine ring has three metabolic precursors: bicarbonate, amide group of glutamine,
PRPP is also required.
There is a 6-step pathway for de novo synthesis of UMP:
1) glutamine combines with bicarbonate ion + 2ATPs to yield carbamoyl phosphate +
2) carbamoyl phosphate combines with aspartate via aspartate transcarbamolyase to form
carbamoyl aspartate (product contains all the atoms necessary for pyrimidine ring).
3) carbamoyl phosphate is cyclized enzymatically to form L- dihydroorotate.
4) L-dihydroorotate is oxidized by dihydroorotate dehydrogenase to form orotate; eremoved
from substrate are transferred to ubiquinone ---> O2 to ETS.
5) Orotate replaces pyrophosphate group of PRPP to form orotidine 5’-monophosphate(OMP)
6) OMP is decarboxylated by OMP decarboxylase to form uridine 5’-monophosphate (UMP)
Dihydroorotate is produced in the cytosol, then passes through the outer mitochondrial membrane.
Enzyme dihydroorotate DH is on outer surface of inner mitochondrial membrane
Orotate then moves back into cytosol
Regulation of UMP synthesis:
asparate carbamoylase (ATCase)- main regulatory enzyme
Inhibited by UTP and CTP
Activated by ATP
Keeps purines and pyrimidines in equal amounts
Synthesis of CTP
Formation of CTP from UMP in three reactions (see pathway sheet).
Regulation of pathway is via CTP synthetase
- allosterically inhibited by CTP
Deoxyribonucleotides are formed from ribonucleotides by ribonucleoside diphosphate reductase.
Energy to fuel reduction comes from NADPH.
There are really three proteins involved:
1) thioredoxin reductase
2) thioredoxin
3) ribonucleotide reductase
Once dADP, dGDP, and dCDP are formed, they are phosphorylated by nucleoside diphosphate
Regulation of ribonucleoside diphosphate reductase is complex because there are 2 regulatory
1) Activity site - a.k.a. allosteric site - controls catalytic site
2) Specificity site - also allosterically regulated- controls substrate specificity
If ATP is bound in activity, enzyme is ACTIVE
If dATP or ATP is bound, reductase is pyrimidine specific
CDP --> dCDP
UDP --> dUDP
Binding of dTTP to specificity site causes enzyme to take GDP --> dGDP.
Binding of dGTP to specificity site causes enzyme to take ADP --> dADP.
Synthesis of Deoxythymidylate (dTMP) by Methylation of dUMP
dTMP is formed from dUMP, which is formed by any of the following:
dUDP + ADP dUMP + ATP enzyme is nucleoside monophosphate kinase
dCMP + H2O dUMP + NH4
dUMP is converted to dTMP by thymidylate synthase
Methyl group donor is methylene tetrahydrofolate
Many cancer drugs inhibit the activity of thymidylate synthase and dihydrofolate
reductase --> decreased levels of dTMP synthesis --> decreased DNA synthesis
Purine Catabolism
Many organisms convert purine nucleotides to uric acid (see pathway sheet)
AMP ---> IMP ---> hypoxanthine ---->
GMP --> xanthine ----->
High serum levels of uric acid may lead to gout
Inflammation of joints is due to precipitation of sodium urate crystals
Kidneys may also be damaged by deposition of crystals
Gout is thought to be an inherited metabolic disease
Some patients with gout have a partial deficiency of HGPRTase
- leads to reduced synthesis of GMP and IMP by salvage pathway
- causes increase in PRPP levels --> increased purine biosynthesis by de novo pathway
Gout can also be caused by increased levels of PRPP caused by a yperactive synthetase
Gout can be treated with allopurinol, an analog of hypoxanthine --> ultimately acts as an
inhibitor of xanthine oxidase; called suicide inhibition
Lesch-Nyhan syndrome
Total lack of HGPRTase.
Results in compulsive self-destructive behavior.
Self-mutilation, mental deficiency, spasticity.
Elevated levels of PRPP ---> increased rate of purine biosynthesis by de novo pathway --->
overproduction of uric acid.
Possible that brain may rely heavily on salvage pathway for IMP and GMP synthesis.
Shows that abnormal behavior can be caused by absence of a single enzyme.
Pyrimidine Catabolism
Begins with the hydrolysis of nucleosides and Pi from nucleotides.
Successive reactions produce ribose 1-phosphate or deoxyribose 1-phosphate.
nucleosides Pi
ribose 1-phosphate
OR + thymine OR uracil
deoxyribose 1-phosphate
Thymine is ultimately broken down to succinyl CoA.
Uracil and cytosine are broken down into alanine, then acetyl CoA.

Amino Acid Metabolism

Will be interested in two things:
1) origin of nitrogen atoms and their incorporation into amino group
2) origin of carbon skeletons
Nitrogen fixation
Gaseous nitrogen is chemically unreactive due to strong triple bond.
To reduce nitrogen gas to ammonia takes a strong enzyme --> reaction is called nitrogen fixation.
Only a few organisms are capable of fixing nitrogen and assembling amino acids from that.
Higher organisms cannot form NH4
from atmospheric N2.
Bacteria and blue-green algae (photosynthetic procaryotes) can because they possess nitrogenase.
Enzyme has two subunits:
1) strong reductase - has Fe-S cluster that supplies e- to second subunit
2) two re-dox centers, one of which is a nitrogenase
Composed of iron and molybdenum that reduces N2 to NH4
Reaction is ATP-dependent, but unstable in the presence of oxygen.
Enzyme is present in Rhizobium, symbiotic bacterium in roots of legumes (i.e. soybeans)
Nodules are pink inside due to presence of leghemoglobin (legume hemoglobin) that binds to oxygen
to keep environment around enzyme low in oxygen (nitrogen fixation requires the absence of
Plants and microorganisms can obtain NH3 by reducing nitrate (NO3
-) and nitrite (NO2
) --> used to
make amino acids, nucleotides, phospholipids.
Assimilation of Ammonia
Assimilation into amino acids occurs through glutamate and glutamine.
-amino group of most amino acids comes from -amino group of glutamate by transamination.
Glutamine contributes its side-chain nitrogen in other biosynthetic reactions.
+ -ketoglutarate glutamate + H2O
glutamate dehydrogenase
Another reaction that occurs in some animals is the incorporation of ammonia into glutamine via
glutamine synthetase:
glutamate + NH4
+ ATP glutamine + ADP + Pi + H
When ammonium ion is limiting, most of glutamate is made by action of both enzymes to produce the
following (sum of both reactions):
+ -ketoglutarate + NADPH + ATP glutamate + NADP
+ ADP + Pi
Transamination Reactions
Having assimilated the ammonia, synthesis of nearly all amino acids is done via tranamination
Glutamate is a key intermediate in amino acid metabolism
Amino group is transferred to produce the corresponding -amino acid.
-amino acid1 -keto acid2 -keto acid1 -amino acid2
Origins of Carbon Skeletons of the Amino Acids
Amino acids that must be supplied in diet are termed essential; others are nonessential.
Although the biosynthesis of specific amino acids is diverse, they all share a common feature -
carbon skeletons come from intermediates of glycolysis, PPP, or citric acid cycle.
There are only six biosynthetic families:
1) Derived from oxaloacetate --> Asp, Asn, Met, Thr, Ile, Lys
2) Drived from pyruvate --> Ala, Val, Leu
3) Derived from ribose 5-phosphate --> His
4) Derived from PEP and erythrose 4-phosphate --> Phe, Tyr, Trp
5) Derived from a-ketoglutarate --> Glu, Gln, Pro, Arg
6) Derived from 3-phosphoglycerate --> Ser, Cys, Gly
Porphyrin Synthesis
First step in biosynthesis of porphyrins is condensation of glycine and succinyl CoA to form -
aminolevulinate via -aminolevulinate synthase.
Translation of mRNA of this enzyme is feedback-inhibited by heme
Second step involves condensation of two molecules of -aminolevulinate to form porphobilinogen;
catalyzed by -aminolevulinate dehydrase.
Third step involves condensation of four porphobilinogens to form a linear tetrapyrrole via
porphobilinogen deaminase.
This is cyclized to form uroporphyrinogen III.
Subsequent reactions alter side chains and degree of saturation of porphyrin ring to form
protoporphyrin IX.
Association of iron atom creates heme; iron atom transported in blood by transferrin.
Inherited or acquired disorders called porphyrias are result of deficiency in an enzyme in heme
biosynthetic pathway.
congenital erythropoietic porphyria - insufficient cosynthase (cyclizes tetrapyrrole)
Lots of uroporphyrinogen I, a useless isomer are made
RBCs prematurely destroyed
Patient’s urine is red because of excretion of uroporphyrin I
Heme Degradation:
Old RBCs are removed from circulation and degraded by spleen.
Apoprotein part of hemoglobin is hydrolyzed into amino acids.
First step in degradation of heme group is cleavage of -methene bridge to form biliverdin, a linear
tetrapyrrole; catalyzed by heme oxygenase; methene bridge released as CO.
Second step involved reduction of central methene bridge to form bilirubin; catalyzed by biliverdin
Bilirubin is complexed with serum albumin --> liver --> sugar residues added to propionate side
2 glucuronates attached to bilirubin are secreted in bile.
Jaundice - yellow pigmentation in sclera of eye and in skin --> excessive bilirubin levels in blood
Caused by excessive breakdown of RBCs, impaired liver function, mechanical obstruction of
bile duct.
Common in newborns as fetal hemoglobin is broken down and replaced by adult hemoglobin.
Excess amino acids (those not used for protein synthesis or synthesis of other macromolecules)
cannot be stored.
Surplus amino acids are used as metabolic fuel.
-amino group is removed; carbon skeleton is converted into major metabolic intermediate
Amino group converted to urea; carbon skeletons converted into acetyl CoA, acetoacetyl CoA,
pyruvate, or citric acid intermediate.
Fatty acids, ketone bodies, and glucose can be formed from amino acids.
Major site of amino acid degradation is the liver.
First step is the transfer of -amino group to -ketoglutarate to form glutamate, which is
oxidatively deaminated to yield NH4
(see pathway sheet).
Some of NH4
+ is consumed in biosynthesis of nitrogen compounds; most terrestrial vertebrates
convert NH4
+ into urea, which is then excreted (considered ureotelic).
Terrestrial reptiles and birds convert NH4
into uric acid for excretion (considered uricotelic).
Aquatic animals excrete NH4+ (considered ammontelic).
In terrestrial vertebrates NH4
+ is converted to urea via urea cycle.
One of nitrogen atoms in urea is transferred from aspartate; other is derived from NH4
; carbon
atom comes from CO2.
There are six steps of the urea cycle:
1) Bicarbonate ion, NH4
and 2 ATP necessary to form carbamoyl phosphate via carbamoyl
phosphate synthetase I (found in mitochondrial matrix).
2) Carbamoyl phosphate and ornithine (carrier or carbon and nitrogen atoms; an amino acid,
but not a building block of proteins) combine to form citrulline via ornithine
3) Citruilline is transported out of mitochondrial matrix in exchange for ornithine
4) Citruilline condenses with aspartate --> arginosuccinate via an ATP-dependent reaction via
arginosuccinate synthetase
5) Arginosuccinate cleaved to form fumarate and arginine via arginosuccinate lyase
fumarate --> malate--> oxaloacetate --> gluconeogenesis
oxaloacetate has four possible fates:
1) transamination to aspartate
2) conversion into glucose via gluconeogenesis
3) condensation with acetyl CoA to form citrate
4) conversion into pyruvate
6) Two -NH2 groups and terminal carbon of arginine cleaved to form ornithine and urea via
Ornithine is transported into mitochondrion to repeat cycle
Overall reaction:
CO2 + NH4
+ + 3 ATP + aspartate + 2 H2O ---> urea + 2 ADP + 2 Pi + AMP + PPi + fumarate
Inherited defects in urea cycle:
1) Blockage of carbamoyl phosphate synthesis leads to hyperammonemia (elevated levels of
ammonia in blood)
2) argininosuccinase deficiency
Providing surplus of arginine in diet and restricting total protein intake
Nitrogen is excreted in the form of argininosuccinate
3) carbamoyl phosphate synthetase deficiency or ornithine transcarbamoylase deficiency
Excess nitrogen accumulates in glycine and glutamine; must then get rid of these
amino acids
Done by supplementation with benzoate and phenylacetate (both substitute for urea
in the disposal of nitrogen)
benzoate --> benzoyl CoA --> hippurate
phenylacetate --> phenylacetyl CoA --> phenylacetylglutamine
Fate of Carbon Skeleton of Amino Acids
Used to form major metabolic intermediates that can be converted into glucose or oxidized by
citric acid cycle.
All 20 amino acids are funneled into seven molecules:
1) pyruvate
2) acetyl CoA
3) acetoacetyl CoA
4) -ketoglutarate
5) succinyl CoA
6) fumarate
7) oxaloacetate
Those that are degraded to acetyl CoA or acetoacetyl Coa are termed ketogenic because they give
rise to ketone bodies.
Those that are degraded to pyruvate or citric acid cycle intermediates are termed glucogenic.
Leucine and lysine are only ketogenic --> cannot be converted to glucose
Isoleucine, phenylalanine, tryptophan, tyrosine are both.
All others are glucogenic only.
C3 family (alanine, serine, cysteine) ---> pyruvate
C4 family(aspartate and asparagine) ---> oxaloacetate
C5 family (glutamine, proline, arginine, histidine) ---> glutamate ---> -ketoglutarate
Methionine, isoleucine, valine, threonine --> succinyl CoA
Leucine --> acetyl CoA and acetoacetate
Phenylalanine and tyrosine --> acetoacetate and fumarate
Tryptophan --> pyruvate
Regulation of the Urea Cycle
The main allosteric enzyme is glutamate dehydrogenase.
It is inhibited by high GTP and ATP levels.
It is stimulated by high GDP and ADP levels.

Lipid Metabolism

Fatty acids have four major physiologic roles in the cell:
Building blocks of phospholipids and glycolipids
Added onto proteins to create lipoproteins, which targets them to membrane
Fuel molecules - source of ATP
Fatty acid derivatives serve as hormones and intracellular messengers
Absorption and Mobilization of Fatty Acids
Most lipids are triacylglycerols, some are phospholipids and cholesterol.
Digestion occurs primarily in the small intestine.
Fat particles are coated with bile salts (amphipathic) from gall bladder.
Degraded by pancreatic lipase (hydrolyzes C-1 and C-3 ---> 2 fatty acids and 2-
Can then be absorbed by intestinal epithelial cells; bile salts are recirculated after
being absorbed by the intestinal epithelial cells.
In the cells, fatty acids are converted by fatty acyl CoA molecules.
Phospholipids are hydrolyzed by pancreatic phospholipases, primarily phospholipase
Cholesterol esters are hydrolyzed by esterases to form free cholesterol, which is
solubilized by bile salts and absorbed by the cells.
Lipids are transported throughout the body as lipoproteins.
Lipoproteins consist of a lipid (tryacylglycerol, cholesterol, cholesterol ester) core
with amphipathic molecules forming layer on outside.
Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids
and contain cell-targeting signals.
Lipoproteins classified according to their densities:
o chylomicrons - contain dietary triacylglycerols
o chylomicron remnants - contain dietary cholesterol esters
o very low density lipoproteins (VLDLs) - transport endogenous
triacylglycerols, which are hydrolyzed by lipoprotein lipase at capillary
o intermediate-density lipoproteins (IDL) - contain endogenous cholesterol
esters, which are taken up by liver cells via receptor-mediated endocytosis
and converted to LDLs
o low-density lipoproteins (LDL) - contain endogenous cholesterol esters,
which are taken up by liver cells via receptor-mediated endocytosis; major
carrier of cholesterol in blood; regulates de novo cholesterol synthesis at
level of target cell
o high-density lipoproteins - contain endogenous cholesterol esters released
from dying cells and membranes undergoing turnover
Storage of Fatty Acids
Triacylglycerols are transported as chylomicrons and VLDLs to adipose tissue;
there, they are hydrolyzed to fatty acids, which enter adipocytes and are esterified
for storage.
Mobilization is controlled by hormones, particularly epinephrine, which binds to -
adrenergic receptors on adipocyte membrane --> protein kinase A activated -->
phosphorylates hormone-sensitive lipase --> converts triacylglycerols to free fatty
acids and monoacylglycerols.
Insulin inhibits lipid mobilization (example of reciprocal regulation).
Monoacylglycerols formed are phosphorylated and oxidized to DHAP (intermediate
of glycolysis and gluconeogenesis).
glycerol glycerol 3-phosphate dihydroxyacetone
glycerol kinase glycerol phosphate
Can be converted to glucose (gluconeogenesis) or pyruvate (glycolysis) in the liver.
Fatty Acid Oxidation (-oxidation)
Fatty acids are degraded by oxidation of the carbon by -oxidation.
Pathway that removes 2-C units at a time --> acetyl CoA --> citric acid cycle --> ATP
There are three stages in -oxidation:
o Activation of fatty acids in cytosol catalyzed by acyl CoA synthetase; two
high energy bonds are broken to produce AMP
o 2) Transport of fatty acyl CoA into mitochondria via carnitine shuttle
o 3) -oxidation - cyclic pathway in which many of the same enzymes are used
repeatedly (see pathway sheet)
-oxidation of odd chain and unsaturated fatty acids
Odd chain fatty acids undergo -oxidation until propionyl CoA is formed.
Propionyl CoA is then converted to succinyl CoA, which then enters the Krebs cycle.
See pathway sheet for details
Unsaturated fatty acids need two additional enzymes besides those of -oxidation.
o enoyl-CoA isomerase
o 2,4-dienoyl-CoA reductase
How the pathway looks depends upon the location of the double bond, but there are
two possibilities.
See pathway sheets for details.
ATP generation from Fatty Acid Oxidation:
Can be estimated from the amount of acetyl CoA, QH2, and NADH produced.
See pathway sheet.
Regulation of Fatty Acid Oxidation
Already talked about fatty acid mobilization via epinephrine.
Net result is high concentrations of acetyl CoA and NADH via -oxidation.
Both molecules allosterically inhibit pyruvate dehydrogenase complex.
Most of acetyl CoA produced goes to Krebs cycle; during periods of fasting, excess
acetyl CoA is produced, too much for Krebs cycle.
Also in diabetes, oxaloacetate is used to form glucose by gluconeogenesis -->
concentration of oxaloacetate is lowered.
Result is the diversion of acetyl CoA to form acetoacetate and 3-hydroxybutyrate;
these two molecules plus acetone are known as ketone bodies.
Acetoacetate is formed via the following reactions:
CoA CoA acetyl CoA
2 acetyl CoA 3-hydroxy- acetoacetate
HMG-CoA lyase
3-methylglutaryl CoA
+ -hydroxy H
+ butyrate CO2
3-hydroxybutyrate acetone
The major site of ketone body synthesis is the liver, within the mitochondrial matrix
---> transported to the bloodstream.
Acetoacetate and 3-hydroxybutyrate are used in respiration and are important
sources of energy.
Cardiac muscle and the renal cortex perferentially use acetoacetate over glucose.
Glucose is used by brain and RBCs; in brain, ketone bodies substitute for glucose as
fuel because the brain cannot undergo gluconeogenesis.
Acetoacetate can be converted to acetyl CoA and oxidized in citric acid cycle only in
nonhepatic tissues.
Diabetes (insulin-dependent diabetes mellitus; IDDM)
Decreased insulin secretion by beta cells of pancreas; could be caused by viruses (?)
Juvenile onset
Patients are thin, hyperglycemic, dehydrated, polyuric (pee a lot), hungry, thirsty
In these patients, glycogen mobilization, gluconeogenesis, fatty acid oxidation occurs ---
> massive ketone body production; also, some of the glucose is in urine (tends to pull
water out of body) ----> diabetic ketoacidosis
Important features of this pathway:
1) Synthesis takes place in cytosol; -oxidation takes place in mitochondrial matrix.
2) Intermediates are bound to sulfhydral groups of acyl carrier protein (ACP);
intermediates of -oxidation are bonded to CoA
3) Growing fatty acid chain is elongated by sequential addition of two-carbon units
derived from acetyl CoA
4) Reducing power comes from NADPH; oxidants in -oxidation are NAD
+ and FAD
5) Elongation of fatty acid stops when palmitate (C16) is formed; further elongation and
insertion of double bonds carried out later by other enzymes
Fatty acid synthesis takes place in three stages:
1) Mitochondrial acetyl CoA is transported into cytosol via citrate transport system
Acetyl CoA is condensed with oxaloacetate to form citrate ---> antiported out with
inward movement of anion
Citrate cleaved by cytosolic citrate lyase --> oxaloacetate + acetyl CoA
2) Formation of malonyl CoA
Acetyl CoA carboxylase is key regulatory enzyme
Influenced by glucagon --> inactivates enzyme in liver
Epinephrine inactivates enzyme in adipocytes
Citrate allosterically activates enzyme
Fatty acyl CoA allosterically inhibits enzyme
3) Assembly of fatty acid chain via fatty acid synthase
Consists of five separate stages:
1) Loading - acetyl CoA and malonyl CoA are attached to acyl carrier protein
2) Condensation - both are condensed by fatty acid synthase to from
3) Reduction - NADPH is oxidized to form hydroxybutyryl ACP
4) Dehydration - formation of double bond
5) Reduction - NADPH is source of e
and H
to form butyryl-ACP
Last four steps are repeated, each time with malonyl-ACP to elongate chain, until palmitate
is produced.
Overall reaction:
acetyl CoA + 7 malonyl CoA + 14 NADPH + 20 H
---> palmitate + 7CO2 + 14 NADP
+ 8 HS-CoA + 6
Regulation of Fatty Acid Synthesis
Metabolism of fatty acids is under hormonal regulation by glucagons, epinephrine,
and insulin.
Fatty acid synthesis is maximal when carbohydrate and energy are plentiful.
Important points of control are release of fatty acids from adipocytes and
regulation of carnitine acyltransferase I in the liver.
High insulin levels also stimulate formation of malonyl CoA, which allosterically
inhibits carnitine acyltransferase I _ fatty acids remain in cytosol and are not
transported to mitochondria for oxidation.
Key regulatory enzyme is acetyl-CoA carboxylase (catalyzes first committed step
in fatty acid synthesis).
Insulin stimulates fatty acid synthesis and inhibits hydrolysis of stored
Glucagon and epinephrine inhibit fatty acid synthesis (enzyme is phosphorylated by
protein kinase A; removal of phosphate group catalyzed by protein phosphatase 2A).
Citrate is an allosteric activator, but its biological relevance has not been
Fatty acyl CoA acts as an inhibitor.
Palmitoyl CoA and AMP are allosteric inhibitors.
Synthesis of Eicosanoids
Precursors for eicosanoids are 20-carbon polyunsaturated fatty acids such as
Part of inner leaflet of cell membrane.
There are two classes of eicosanoids:
1) prostaglandins and thromboxanes
Synthesized by enzyme cyclooxygenase
Localized molecules such as thromboxane A2, prostaglandins, prostacyclin ae
Thromboxane A2 leads to platelet aggregation and blood clots _ reduced
blood flow in tissues.
Aspirin binds irreversibly to COX enzymes and prevents prostaglandin
2) leukotrienes
Produced by lipoxygenases.
Products were once called “slow-acting substances of anaphylaxis”,
responsible for fatal effects of some immunizations.
Synthesis of Triacylglycerols and Glycerophospholipids
Most fatty acids are esterified as triacylglycerols or glycerophospholipids.
Intermediate molecule in synthesis of these two molecules is phosphatidic acid or
There are two pathways:
1) de novo – “from scratch”
2) salvage pathway - uses “old” pieces and parts to make new molecules
Synthesis of phosphatidate:
Common intermediate in synthesis of phosphoglycerides and triacylglycerols
Formed from glycerol 3-phosphate and 2 acetyl CoA molecules
Enzyme is glycerol phosphate acyltransferase
Synthesis of triacylglycerols and neutral phospholipids:
Uses phosphatidate, which is dephosphorylated to produce 1,2-diacylglycerol
If acetylated ---> triacylglyerol
If reacted with nucleotide derivative --> phosphatidylcholine or
Synthesis of acidic phospholipids:
Uses phosphatidate and reacts it with CTP ---> CDP-diacylglycerol
Addition of serine --> phosphatidylserine
Addition of inositol ---> phosphatidylinositol
In mammals, phosphatidylserine and phosphatidylethanolamine can be interconverted
- base-exchange occurs in ER.
Decarboxylation occurs in mitochondria and procaryotes
Synthesis of Sphingolipids
All have C18 unsaturated alcohol (sphingosine) as structural backbone, rather than
Palmitoyl CoA and serine condense ---> dehydrosphinganine ---> sphingosine
Acetylation of amino group of sphingosine ---> ceramide
Substitution of terminal hydroxyl group gives:
sphingomyelin -- addition of phosphatidylcholine
cerebroside -- substitute UDP-glucose or UDP-galactose
gangliosides -- substitute oligosaccharide
Tay-Sachs disease = inherited disorder of ganglioside breakdown.
Deficient or missing enzyme is -N-acetylhexosaminidase, which removes the
terminal N-acetylgalactosamine residue from its ganglioside.
One in 30 Jewish Americans of eastern European descent are carriers of a
defective allele.
Can be diagnosed during fetal development by assaying amniotic fluid for enzyme
Causes weakness, retarded psychomotor development, blindness by age two, and
death around age three.
Synthesis of Cholesterol
Precursor of steroid hormones and bile salts.
Most cholesterol is synthesized in liver cells, although most animal cells can synthesize
Starts with 3 molecules of acetyl CoA to form 3-hydroxy-3-methyl-glutaryl CoA, which
is reduced to mevalonate (C6) by HMG-CoA reductase (first committed step of
cholesterol synthesis)
Amount of cholesterol formation by liver and intestine is highly responsive to cellular
levels of cholesterol.
Enzyme HMG-CoA reductase is controlled in multiple ways:
1) Rate of enzyme synthesis is controlled by sterol regulatory element (SRE); SRE
inhibits mRNA production
2) Translation of reductase mRNA is inhibited by nonsterol metabolites derived
from mevalonate
3) Degradation of the enzyme occurs at high enzyme levels
4) Phosphorylation of enzyme
If enzyme is phosphorylated via glucagon pathway --> decreased activity-->
cholesterol synthesis ceases when ATP levels are low
If enzyme is dephosphorylated via insulin pathway --> increased activity
Cells outside liver and intestine obtain cholesterol from blood instead of synthesizing it
de novo.
Steps in the uptake of cholesterol by LDL pathway:
1) apolipoprotein on surface of LDL particle binds to receptor on membrane of
nonhepatic cells
2) LDL-receptor complex internalized by endocytosis
3) vesicles formed fuse with lysosomes, which breaks apart protein part of lipoprotein
to amino acids and hydrolyzes cholesterol esters
4) released unesterified cholesterol can be used for membrane biosynthesis or be
reesterified for storage
Defects in LDL receptor lead to familial hypercholesterolemia (FH), in which
cholesterol and LDL levels are markedly elevated.
Result is deposition of cholesterol in tissues because of high levels of LDL-cholesterol in
Heterozygotes suffer from atherosclerosis and increased risk of stroke
Homozygotes usually die in childhood from coronary artery disease
Disease is the result of an absence (homozygotes) or reduction (heterozygotes) in
number of LDL receptors.
LDL entry into liver and other cells is impaired.
Drug therapy can help heterozygotes
1) can inhibit intestinal absorption of bile salts (which promote absorption of dietary
2) lovastatin - competitive inhibitor of HMG-CoA reductase ---> blocks cholesterol

- Lipids and Membranes

Lipids are water-insoluble that are either hydrophobic (nonpolar) or amphipathic (polar and nonpolar
There are many types of lipids:
1) fatty acids
The simplest with structural formula of R-COOH where R = hydrocarbon chain.
They differ from each other by the length of the tail, degree of unsaturation, and position
of double bonds.
pKa of -COOH is 4.5-5.0 --> ionized at physiological pH.
If there is no double bond, the fatty acid is saturated.
If there is at least one double bond, the fatty acid is unsaturated.
Monounsaturated fatty acids contain 1 double bond; polyunsaturated fatty acids have >2
double bonds.
IUPAC nomenclature =n represents where double bond occurs as you count from the
carboxyl end (see Table 9.1).
e.g. -enoate one double bond
-dienoate 2 “
-trienoate 3 “
-tetraenoate 4 “
Can also use a colon separating 2 numbers, where the first number represents the number
of carbon atoms and the second number indicates the location of the double bonds.
e.g. linoleate 18:29,12 or cis,cis -9,12octadecadienoate
Physical properties differ between saturated and unsaturated fatty acids.
Saturated = solid at RT; often animal source; e.g. lard
Unsaturated = liquid at RT; plant source; e.g. vegetable oil
The length of the hydrocarbon tails influences the melting point.
As the length of tails increases, melting points increases due to number of van der Waals
Also affecting the melting point is the degree of unsaturation.
As the degree of unsaturation increases, fatty acids become more fluid--> melting point
decreases ( kinks in tails decrease number of van der Waals interactions).
Fatty acids are also an important sources of energy.
9 kcal/g vs. 4 kcal/g for carbohydrates and proteins.
2) triacylglycerols
Also called triglycerides.
Made of 3 fatty acyl residues esterified to glycerol.
Very hydrophobic, neutral in charge ---> can be stored in anhydrous form.
Long chain, saturated triacylglycerols are solid at RT (fats).
Shorter chain, unsaturated triacylglycerols are liquid at RT (oils).
Lipids in our diet are usually ingested as triacylglycerols and broken down by lipases to
release fatty acids from their glycerol backbones
Also occurs in the presence of detergents called bile salts.
_ Form micelles around fatty acids that allow them to be absorbed by
intestinal epithelial cells.
_ Transported through the body as lipoproteins.
3) glycerophospholipids
Main components of cell membranes.
Are amphipathic and form bilayers.
All use glycerol 3-phosphate as backbone.
Simplest is phosphatidate = 2 fatty acyl groups esterified to glycerol 3-
Often, phosphate is esterified to another alcohol to form...
_ phosphatidylethanolamine
_ phosphatidylserine
_ phosphatidylcholine
Enzymes called phospholipases break down biological membranes.
_ A-1 = hydrolysis of ester bond at C-1.
_ A-2 = hydrolysis of ester bond at C-2; found in pancreatic juice.
_ C = hydrolysis of P-O bond between glycerol and phosphate to create
_ D = same
4) sphingolipids
Second most important membrane constituent.
Very abundant in mammalian CNS.
Backbone is sphingosine (unbranched 18 carbon alcohol with 1 trans C=C
between C-4 and C-5), NH3
+ group at C-2, hydroxyl groups at C-1 and C-3.
Ceramides are intermediates of sphingolipid synthesis.
There are three families of sphingolipids:
1) sphingomyelin - phosphocholine attached to C-1 hydroxyl group of ceramide;
present in the myelin sheaths around some peripheral nerves.
2) 2)cerebrosides - glycosphingolipid; has 1 monosaccharide (galactose) attached by
-glycosidic linkage to C-1 of ceramide; most common is galactocerebroside,
which is abundant in nervous tissue.
3) gangliosides - glycosphingolipid containing N-acetylneuraminic acid; present on all
cell surfaces.
Hydrocarbon tails embedded in membrane with oligosaccharides
facing extracellularly.
Probably used as cell surface markers, e.g. ABO blood group
Inherited defects in ganglioside metabolism --> diseases, such as Tay-Sachs disease.
5) steroids
Called isoprenoids because their structure is similar to isoprene.
Have 4 fused rings: 3 6-membered rings (A,B,C) and 1 5-membered ring (D).
Cholesterol is an important component of cell membranes of animals, but rare in plants and
absent in procaryotes.
Also have mammalian steroid hormones (estrogen, androgens) and bile salts.
Differ in length of side chain at C-17, number and location of methyl groups, double bonds,
Cholesterol’s role in membranes is to broaden the phase transition of
cell membranes ---> increases membrane fluidity because cholesterol
disrupts packing of fatty acyl chains.
6) other lipids not found in membranes
waxes - nonpolar esters of long chain fatty acids and alcohols
very water insoluble
high melting point --> solid at outdoor/RT.
Roles: protective coatings of leaves, fruits, fur, feathers,
eicosanoids - 20 carbon polyunsaturated fatty acids
e.g. prostaglandins - affect smooth muscle --> cause
constriction; bronchial constriction of asthmatics; uterine
contraction during labor
limonene - smell of lemons
bactoprenol - involved in cell wall synthesis
juvenile hormone I - larval development of insects
Biological Membranes
Central transport of ions and molecules into and out of the cell.
Generate proton gradients for ATP production by oxidative phosphorylation.
Receptors bind extracellular signals and transduce the signal to cell interior.
Glycerophospholipids and glycosphingolipids form bilayers.
Noncovalent interactions hold lipids together.
5-6 nm thick and made of 2 leaflets to form a lipid bilayer driven by hydrophobic
About 40% lipid and 50% proteins by mass, with about 10% carbohydrates.
Protein and lipid composition varies among membranes but all have same basic structure -->
Singer and Nicholson fluid mosaic model in 1972.
Membrane fluidity:
Lipids can undergo lateral diffusion; can move about 2 m/sec.
Can undergo transverse diffusion (one leaflet to another) but very rare.
Membrane has an asymmetrical lipid distribution that is maintained by flippases or
translocases that are ATP-driven.
In 1970, Frye and Edidin demonstrated that proteins are also capable of diffusion by using
heterocaryons, but occurs at a rate that is 100-500 times slower than lipids.
Most membrane protein diffusion is limited by aggregation or attachment to cytoskeleton.
Can examine distribution of membrane proteins by freeze-fracture electron microscopy.
Membrane fluidity is dependent upon the flexibility of fatty acyl chains.
Fully extended saturated fatty acyl chains show maximum van der Waals
When heated, the chains become disordered --> less interactions --> membrane
“shrinks” in size due to less extension of tails --> due to rotation around C-C
For lipids with unsaturated acyl chains, kink disrupts ordered packing and
increases membrane fluidity --> decreases phase transition temperature
(becomes more fluid at lower temperature).
Some organisms can alter their membrane fluidity by adjusting the ratio of
unsaturated to saturated fatty acids.
e.g. bacteria grown at low temperature increase the proportion of
unsaturated fatty acyl groups.
e.g. warm-blooded animals have less variability in that ratio because of
the lack of temperature fluctuations.
exception: reindeer leg has increased number of fatty acyl groups as
get closer to hoof --> membrane can remain more fluid at lower
Cholesterol also affects membrane fluidity.
Accounts for 20-25% of lipid mass of membrane.
Broadens the phase-transition temperature.
Intercalation of cholesterol between membrane lipids restricts
mobility of fatty acyl chains ---> fluidity decreases.
Helps maintain constant membrane fluidity despite changes in
temperature and degree of fatty acid saturation.


Depends upon substrate availability and energy demands in the cell.
Important substrates are NADH, O2, and ADP.
As ATP is used, more ADP is available, translocated through adenine nucleotide translocase
--> electron transport increases.
Known as respiratory control.
Helps to replenish ATP pool in the cell, which is kept nearly constant.
Rates of glycolysis, citric acid cycle, and electron transport system are matched to a cell’s
ATP requirements.
Proton gradient can be short-circuited to generate heat
Found in brown adipose tissue in newborn mammals and animals that hibernate, and animals
adapted to cold conditions
A protein called thermogenin forms a proton channel in inner mitochondrial membrane -->
dissipates proton gradient, but electrons still flow --> heat production
Pathway is activated by fatty acids from triacylglycerol catabolism from epinephrine
Superoxide Production
Even though cytochrome oxidase and other proteins that reduce oxygen have been designed not to
release O2
.- (superoxide anion), it still does happen.
Protonation of superoxide anion yields hydroperoxyl radical (HO2
.), which can react with another
molecule to produce H2O2.
Enzyme superoxide dismutase catalyzes this reaction
.- + O2
.- ----------------------------> H2O2 + O2
superoxide dismutase
Recent findings have indicated that superoxide dismutase mutations can cause amyotrophic lateral
sclerosis (Lou Gehrig’s disease), in which motor neurons in brain and spinal cord degenerate.
The hydrogen peroxide formed is scavenged by catalase:
H2O2 + H2O2 2H2O + O2
Peroxidases catalyze an analogous reaction:
ROOH + AH2 ROH + H2O + A

Monday, 30 January 2017

Kidneys Functions Excretion: nitrogenous wastes (urea, uric acid), excess salts, excess water. Osmoregulation: maintaining the blood at a suitable constant concentration. Homeostasis: maintaining a suitable constant internal environment to sustain efficient metabolism. Urinary System



Excretion: nitrogenous wastes (urea, uric acid), excess salts, excess water.
Osmoregulation: maintaining the blood at a suitable constant concentration.
Homeostasis: maintaining a suitable constant internal environment to sustain efficient metabolism.
Urinary System

Textbook Diagram: urinary system.

The kidneys are a pair of fist-sized red-brown bean-shaped structures.
The kidneys are attached to the back wall of the abdominal cavity.
They lie on either side of the backbone just above the pelvis.
Each kidney receives a good supply of oxygenated blood from the renal artery, a branch of the dorsal aorta.
The renal vein takes the deoxygenated blood from the kidneys to the inferior vena cava.
The blood in the renal vein has less oxygen, salt, urea and uric acid than the renal artery.
Urine is carried to the bladder along the ureter by peristalsis for temporary in the bladder.
A sphincter muscle at the junction of the bladder and urethra regulates the retention and release of urine.
Urine is channelled to the exterior along the urethra.

Kidney Structure

Textbook Diagram: longitudinal section of a kidney showing its internal structure.

A smooth thin protective cover called the capsule surrounds each kidney.
Below the capsule is a thick reddish granular layer, the cortex.
The central part of the series of triangular structures is reddish-brown, the renal pyramids, the tips of which project into the upper expanded end of the ureter known as the pelvis.


Textbook diagram: structure and blood supply of the nephron.

The nephron or renal tubule is the functional unit of the kidney.
The nephron has a number of functionally distinct parts.
Each human kidney has about one million nephrons.
Urine is manufactured by the nephrons.
Production of Urine: Filtration and Selective Reabsorption

Details of Urine Formation


The glomerulus functions as a filter.
The glomerular capillary walls are porous.
The red blood cells, white cells, platelets and plasma proteins are too big to pass through the pores.
Therefore the glomerulus filters the blood.
The filtrate passing into Bowman’s Capsule.
Glomerular filtrate composition is water, glucose, amino acids, vitamins, salts, urea, and uric acid.
About 20% of the plasma volume passes out of the glomerulus.
The filtration is much higher than expected.
The blood pressure is unusually high in the glomerulus.
The blood pressure is generated by the pumping action of the heart.
The high blood pressure in the glomerulus is due to:

The arrangement of blood vessels: arteriole —> capillaries —> arteriole
This arrangement is unusual - normally low-pressure venules follow capillaries.
The efferent arteriole is narrower than the afferent arteriole.
The higher than normal filtration at the glomerular capillaries is known as ultrafiltration.

Selective Reabsorption

Much useful material was lost from the blood into Bowman’s Capsule.
The ‘useful’ materials are taken back into the blood from the nephron.
By de-selection, urea and uric acid remain in the nephron and are excreted in the urine.
Urine is the unabsorbed glomerular filtrate.
Proximal Convoluted Tubule (PCT)

Total reabsorption of glucose and amino acids.
Four fifths of the salts and water are reabsorbed.
Glucose, amino acids and salts are reabsorbed by active transport.
Water is reabsorbed by osmosis.
The cells lining the PCT are rich in mitochondria, which supply the ATP for active transport.
The Loop of Henle

This structure allows the kidney to reabsorb extra water in times of water stress. As a result it is possible for the kidney to produce hypertonic urine, i.e., more concentrated than blood plasma. A Loop of Henle is only present in mammals and birds — the only animals able to produce hypertonic urine.

About 5% of the water from the glomerular filtrate is reabsorbed from the Loop of Henle by osmosis.

The main function of the Loop is to develop an increasingly concentrated medulla. It accomplishes this by acting as a ‘hairpin counter current multiplier’. This allows extra water, if needed, to be absorbed from the collecting duct under the influence of ADH hormone.

Distal Convoluted Tubule (DCT)

Reabsorption of water is by osmosis.
The amount varies depending on the need of the body.
Water reabsorption by the DCT is under the influence of ADH (antidiuretic hormone).
Reabsorption of salt is by active transport.
The amount of salt reabsorbed depends on the needs of the body.
The role of the DCT is crucial in osmoregulation.
Osmoregulation is a major process in homeostasis.


Blood concentration is kept in check by varying the amount of water and salt reabsorbed by the kidneys nephrons.

Blood Concentration Rising

Cause: salty food, water loss due to sweating, inadequate water intake.
Response: increases water reabsorption, decreases salt reabsorption.
Blood Concentration Falling

Cause: excessive water intake, cold weather (sweating less than usual), diet very low on salt.
Response: decreases water reabsorption, increases salt reabsorption.
Note: the greater the excess protein in the diet the greater is the urea content of the urine.

Regulation of Body Fluids by the Kidney
The kidney maintains the blood at the correct composition and concentration by excretion and osmoregulation.

As a result all the other body fluids are kept at optimum condition i.e. tissue fluid and cell cytoplasm.

Role of ADH (antidiuretic hormone)

ADH is secreted to increase water reabsorption by the DCT and collecting duct when blood concentration rises.
Osmoreceptors in the brain’s hypothalamus detect the increase in osmotic pressure of the blood.
This stimulates the pituitary to increase the secretion of ADH into the blood.
ADH is transported everywhere throughout the body in the blood.
The DCT and collecting duct are the target tissues of this hormone.
ADH causes these parts of the nephron to become more permeable to water.
Extra water is now reabsorbed into the blood reducing its concentration back to normal.
The loss of extra water from the filtrate reduces the volume but increases the concentration of the urine.
Major Homeostatic Organs: kidneys, liver, lungs, skin and brain.

Normal distribution about the mean Mode (most frequent) = median (mid) = mean (average value) Bell-shaped/ even distributions of values above and below mean Standard error (SE)

True mean of SE is ±1.96
In a number of samples each sample will have its own mean
Standard error measures how much the value of a sample mean is likely to vary
The greater the standard error, the greater the variation of the mean
Standard deviation (σ)
Measure of the spread of results about the mean of a normal distribution curve
Thinner bell-shape / smaller standard deviation / less variation
Same pattern with bigger bell-shape
Causes of variation
Independent assortment of bivalents at the equator during anaphase I
Chromosomes of bivalents pulled to opposite poles at random
2n different combinations of chromosomes in four haploid cells produced where n is the haploid number of chromosomes
Crossing over between non-sister chromatids during prophase I
At synapsis, non-sister chromatids of homologous pairs cross over at chiasmata
Homologous chromatids (corresponding pieces of genetic material) break and exchange equivalent segments between maternal and paternal chromatids
Results in new combination of genes from the two parents
Fertilization / random fusion of gametes
Genetic difference amongst the zygote
New combinations of alleles
Gene mutation / increased by environmental factors (eg radiation)
Addition / at least one base is added during DNA replication
Deletion / at least one base is not copied (frameshift)
Substitution / at least one base is copied wrongly
Interferences with normal base pairing (A-T;C-G)
Degenerate code / different triplets can code for same amino acids
Discontinuous variation
IMG 5-14-2
Limited number of distinct phenotypes / categories (e.g. blood group)
Strong genetic factor controlled by alleles on one gene
Frequency histogram has separate bars
Unaffected by the environment
Continuous variation
Continuous range of values / class intervals (e.g. human height)
Alleles on many genes located on different chromosomes / polygenic inheritance
Frequency histogram is a smooth (normal distribution) curve
Phenotype is affected by environmental factors
Lower skin temperature activates a gene for pigment production
Diet affects individual's size and health. Malnourishment results in shorter height
Therefore, genes + environment → phenotype (continuous variation)
Advantageous of variation to species
Allows different adaptations / some better adapted
Some survive / reproduce / pass on gene/allele
Allows for changing environment / different environment


Five Kingdoms
Human Activity
Nutrient Cycle

Normal distribution about the mean
Causes of variation
Discontinuous variation
Continuous variation
Advantageous of variation to species