Exam 2 Medical Botany 3850 USF

Mycotoxins

low-molecular weight natural products produced as secondary metabolites by filamentous fungi

Mycotoxicoses

Diseases produced by the exposure to toxic fungal metabolites

Dietary, Respiratory, Dermal......

Endophyte Life Cycle

Mycotoxin "Gold Rush" 1960-1975

Many scientists joined the well-funded search for toxigenic agents produced by fungi

300-400 compounds now recognized as mycotoxins; 12+ groups

The biggest problems with mycotoxicoses

-Heighten vulnerability to microbial diseases

-Worsen the effects of malnutrition

-Interact synergistically with other toxins.

not all toxic compounds produced by fungi are called mycotoxins

Mycotoxins versus vertebrates and other animals

Mycotoxins - LOW conc. vs Ethanol - HIGH conc.

Antibiotics versus Bacteria

Phytotoxins versus Plants

Mushroom Poisons - macroscopic fungi, ingestion because of misidentification

Control of Mycotoxins

Sufficient drying of crops after harvest before storage

Plant breeding

Genetic engineering - enhance antifungal genes

Use of biocontrol agents that target regulatory genes in the mycotoxin development

Improved government screening and regulation programs

Which foods are aflatoxins found in?

peanuts, corn, Brazil Nuts, pistachios, pumpkin seeds, cotton seeds, and watermelon seeds

What common disease is aflatoxin associated with?

Isolated after Turkey X Disease

Consumption of a mold-contaminated peanut meal

What are the four major aflatoxins?

B1, B2, G1 and G2

Which type of aflatoxin is the most potent?

B1 is the most potent natural carcinogen known, unfortunately major aflatoxin produced by toxigenic strains

Which fungi are major producers of aflatoxin?

Aspergillus flavus and Aspergillus parasiticus

What family do Aspergillus flavus and Aspergillus parasiticus belong to?

Trichocomaceae

Problems aflatoxin is causing

Contamination of grain causes:Increased mortality in farm animalsIncreased mortality in farm animalsLowers the value of exported grain as animal feeds

Lowers the value of exported grain as animal feeds

Location of biggest problem is countries where the

- population is facing starvation or regulations the

-population is facing starvation or regulations non-existent or not enforcednon-existent or not enforce

Mechanism of action of aflatoxin

Cytochrome enzymes convert to an epoxide that binds to N7 of guanine.

Guanine is now only able to make 2 hydrogen bonds instead of 3 hydrogen bonds.

Eventual mutation of G/C to A/T

Is aflatoxin a carcinogen?

Human carcinogen- liver cancer

China, Philippines, Thailand, and many African countries

nRisk factor: Hepatitis B

Aflatoxin Structure

Ergot alkaloids

Produced by Claviceps, primarily

a grass pathogen

Claviceps purpurea Family?

(This is a mold that causes food to rot and it makes a hallucinogenic toxin.)

Clavicipitaceae

Ergot Alkaloids History

Common in Europe during Middle Ages

"..noxious pustule in the ear of grain"

Eating cereals infected with a toxic cocktail of alkaloids with ergoline ring systems

St. Anthony's Fire (ergotism)

St Anthony's Fire - bread from contaminated flour

Gangrenous - blood supply to the extremities

Convulsive - affect CNS

195-Last break out in Pont-saint-esprit France

Rye Scientific Name and Family

Secale cereale

Family: {Poaceae}

What is the current state of ergot alkaloid problem?

It is a veterinary problem. Cattle, sheep, pigs, chicken

Ergot Alkaloids Mechanism of Action and Symptoms

Mechanism of action:

-Induce smooth muscle contraction

-Midwives administer to women in labour as a natural product to accelerate uterine contractions

Other Symptoms:

Gangrene, abortions, convulsions, suppression of lactation, hypersensitivity

Sclerocia

Ergot Alkaloids and LSD

1943 - Birth of LSD

-Hoffman - research involved varying the amino alcohol of lysergic acid

-Developed Methergine - control hemorrhaging after childbirth

Continued research...

-Intentionally Ergot Alkaloids and LSD ingested compound #25 and discovered the hallucigenic properties of lysergic acid diethylamide (LSD)

-Marketed as Delysid - unsuccessful treatment of schizophrenia

Ergot Alkaloids Uses in War

MK-ULTRA code name

-After WWII - CIA used as a truth serum for interrogating suspected communists

Ergot Alkaloid Uses in Witchcraft

Hypothesized Salem witchcraft affair probably the result of convulsive ergotism related to consumption of rye with Claviceps ergot alkaloids cocktail

Ergot Alkaloid Uses in Headaches

Ergotamine - used to treat migraine headaches

Ergot Alkaloid Uses in Parkinsons

Ergot derivatives - used in the treatment of Parkinsonism

Ergot Alkaloid Structure

Look for the nitrogens

Fumonisin Structure

The fungal species that produce fumonisin

Fusarium spp.

Alternaria alternata

What family does Fusarium spp. belong to?

Nectriaceae

Sclerotia

A sclerotium (/skləˈroʊʃəm/; pl. sclerotia (/skləˈroʊʃə/),[help 1] is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant until favorable growth conditions return. Sclerotia initially were mistaken for individual organisms and described as separate species until Louis René Tulasne proved in 1853 that sclerotia are only a stage in the life cycle of some fungi.[1] Further investigation showed that this stage appears in many fungi belonging to many diverse groups. Sclerotia are important in the understanding of the life cycle and reproduction of fungi, as a food source, as medicine (for example, ergotamine), and in agricultural blight management.

What family does Alternia alternata belong to?

Pleosporaceae

Fumonisin mechanism of action

- Interferes with sphingolipid biosynthesis (Sphingolipid is a major lipid in the cell membranes of nerve and liver cells)

- Toxin blocks enzymes involved in formation of intermediate lipid ceramide

- Results in an accumulation of sphinganine which has toxic effects

-Cause leukoencephalomalacia (hole in head syndrome) in birds and rabbits

Humans:

Can cause neural tube defects

Linked to esophageal cancer

-Charleston, SC - 7 samples

nIsolated high concentration in corn meal and corn grits

-US city with highest incidence of esophageal cancer among African-Americans

Trichothecene (Type A Group)

T-2 toxin {Non macro cyclic}

Trichothecene (Type B Group)

deoxynivalenol (vomitoxin) {non macrocyclic}

Trichothecene (Macrocyclic)

Satratoxin H. {macrocyclic}

What organisms produce trichothecenes?

Over 60 compounds produced by:

-Fusarium, Phomopsis, Trichoderma, Myrothecium, Stachybotrys, Trichothecium...

stachybotyrs are the most famous and are involved in hurricances etc.

Syptoms of trichothecenes

-Common food & feed contaminants

-Consumption:

Alimentary hemorrhaging and vomiting

-Skin contact:

Dermatitis

Trichothecenes Mechanism of Action

-Extreme potent inhibitors of eukaryotic protein synthesis, specifically peptidyl transferase. Interferes with process of transalation.

Compare to ricin which also affects protein synthesis but target the ribosomes. It inactivates 90,000 ribosomes in one minute.

Trichothenes, Deoxynivalenol

Most common mycotoxin found in grain

-Especially barley

A.k.a. Vomitoxin or food refusal factor

-Farm animal - nausea, vomit, diarrhea, weight loss and food refusal

Trichothecenes, T-2 & diacetoxyscirpenol

Cytotoxic activity

Immunosuppressive effect

Human disease:

-Alimentary toxic aleukia

---Inflammation of skin, vomiting, necrosis of oral cavity, bleeding (nose, mouth & vagina), and CNS problems

Trichothecenes, Stachybotrys

Wet building material harbor organism

--Gypsum board, ceiling tiles, wood fiber board, dust lined A/C vents

Mycotoxin people talk about when referring to Sick-building Syndrome

Shown to cause pulmonary bleeding in infants when exposed for prolonged times

Described as the 10th plague visited on Egypt

which organism produces the mycotoxin that causes the sick-building syndrome? Caused the 10th plague in Egypt?

stachybotrys

Cucurbitaceae (Gourd family)

-Vines (often with tendrils)

-Palmately, 5-lobed leaves

-Imperfect flowers

-Female flowers with 3 carpels

-Pepo fruit

-1000 species

-Highest Portion Used for Food

Example Genus in the Cucurbitaceae Gourd Family

Cucurbita

Citrillus

Trichosanthes

Ecballium

Luffa

Cucurbita genus

Squash, Pumpkin, Gourd

Citrillus Genus

Watermelon

Trichosanthes Genus

Snake Gourd, Gualou (used in medicine in ancient china to break down phlegm)

Ecballium Genus

Squirting Cucumber

Luffa Genus

Loofah fruit and can be used as a scrubbing sponge as well

What are the effects of toxins in the Cucurbitaceae family?

-stomach cramps

-salivation

-diarrhea

-death

Cucurbitacin Toxin

-steroid compound

-antifeedant

-Cucurbitacin A---> Image

-Cucurbitacin E--> Induces apoptosis in human cervical cancer cell lines by upregulating death receptor 5

Trichosanthes cucumerina

Snake Gourd (eat when green and not ripe/red)

Cucurbitacin and Cancer Connection?

Cucurbitacin E--> Induces apoptosis in human cervical cancer cell lines by upregulating death receptor 5

Amaryllidaceae Family (below ground structures to consider)

Allium Genus (onion, garlic, scallion, shallot, leek, chives)

Classified as a true bulb, MONOCOTS

What is a true bulb?

The definition of a bulb is any plant that stores its complete life cycle in an underground storage structure. Bulbs or bulb-like plants are usually perennials. They have a period of growth and flowering. This is followed by a period of dormancy where they die back to ground level at the end of each growing season.

A bulb is comprised of a plant's stem and leaves. The bottom of the bulb is a compacted stem, and roots grow from this part of the bulb. Layers of nutrient-filled leaves sit at the bottom of the bulb and surround a bud that eventually becomes the flower.

FOUND IN MONOCOTS

Solonaceae Family (below ground structures to consider)

Solanum Genus: Potato, Eggplant, Tomato Plants.

This family has tubers which are underground stems that function as food reserves and can bear buds from which new plants can arise.

What is a tuber?

a much thickened underground part of a stem or rhizome, e.g. in the potato, serving as a food reserve and bearing buds from which new plants arise.

Apiaceae Family (below ground structures to consider)

carrot(daucus), parsley, celery. Carrots involve true roots or tap roots.

What is the difference between tap root and fibrous root?

A tap root system has a single main root that grows down. A fibrous root system forms a dense network of roots that is closer to the soil surface. An example of a tap root system is a carrot. Grasses such as wheat, rice, and corn are examples of fibrous root systems.

Convolvulaceae Family (below ground structures to consider)

Ipomea genus (Sweet Potato, morning glories)

Sweet Potato involves enlarged roots which are known as tuberous roots.

What is a tuberous root? How does it differ from a tuber?

A tuberous root is an enlarged fleshy root modified as a storage organ with shoots produced at one end and roots produced at the other. Dahlia. Sweet potato is produced from a tuberous root. Botanically, tuberous roots differ from true tubers because tubers are modified stem tissue.

Araceae Family (below ground structures to consider)

Colocasia genus (taro plant)

Taro has structures called corms which are essentially modified underground stems (corms) that look like a bulb and can give rise to a whole plant. MONOCOTS

What is a corm?

Corms are actually enlarged underground stems that store nutrients, surrounded by papery outer layers. After stems sprout from the corm, buds form on top of the stem. Corms at their center are solid tissue, whereas Bulbs are immature layers of leaves. At the end of the growing season, a new corm typically grows on the base of the spent one, and plants regrow from new corms each season. Usually MONOCOTS

What is a Rhizome?

a continuously growing horizontal underground stem which puts out lateral shoots and adventitious roots at intervals. Ex. Ginger

What toxins do the Amaryllidaceae family produce?

Alkaloids- Lycorine

Raphides- Sharp calcium oxalate structures

Lycorine Structure

Alakloid cotains nitrogen. Search up image unable to put in quizlet

Raphide

a needle-shaped crystal of calcium oxalate occurring in clusters within the tissues of certain plants. Poke mucous membranes and cause large inflammatory response.

What are some toxins found in Daffodils? Explain!

Galantamine- Galantamine has been used for decades in Russia and Eastern Europe for treatments of myasthenia, myopathy, and sensory and motor dysfunction associated with disorders of the central nervous system, and it is now FDA approved in the US for the treatment of Alzheimer's disease and other memory impairments (vascular ones in particular)

Lycorine- Conversely, lycorine isn't used for medicinal purposes - in fact, it has the opposite effect because it's toxic, causing severe vomiting and diarrhoea when ingested. It is present in the daffodil's bulb and therefore is usually consumed accidentally when the bulbs are confused with onions.

Lycorine

-inhibits protein synthesis

-inhibits ascorbic acid synthesis

-inhibts acetylcholinesterase

No good, just a toxin

What are some common Amaryllidaceae family members that flower, are in florida, and are called "lilies"?

Swamp Lily and Garden Lily

What are some dangers for pets in the allium genus?

Allium sativum (garlic)

Allium cepa (onion)

Sulfur compounds: impact on hemoglobin

Discoreaceae Family (below ground structures to consider)

Discorea genus (yams)- They are tubers like potatoes

Euphorbiaceae Family (below ground structures to consider)

Manihot esculenta (Cassava), Ricinus communis (castor bean)

Cassava is classified as a tuberous root.

Solanaceae (Nightshade Family)

tomatoes, potatoes, eggplant, peppers, tomatillo

What are some deadly members of the Solonaceae family?

Brugmansia

•angel's trumpet

Atropa belladonna

•deadly nightshade

Datura

•jimsonweed

Mandragora

•mandrake

Brugmansia- angel's trumpet Picture

Deadly member of the solanaceae family

Atropa belladonna (deadly nightshade)

Deadly member of the solanaceae family

Datura (jimsonweed)

Deadly member of the solanaceae family

mandragora (mandrake)

Deadly member of the solanaceae family

What toxins does the solanaceae family produce?

Tropane Alkaloids (Nitrogen Reading a Book)

Hyoscyamine, Atropine (racemic Mixture of hyoscyamine), Scopolamine (an extra eposide group)

Tropane alkaloids

What are the symptoms caused by tropane alkaloids? What is the mnemonic?

dryness, tachycardia, severe hallucinations, confusion, nonsense speech, amnesia, coma, death

mnemonic for the clinical signs of tropane alkaloid poisoning: "hot as hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter

What is the mechanism of action of tropane akaloids?

•antagonist of muscarinic acetylcholine receptor

•prevent acetylcholine binding

-effects on the parasympathetic nervous system

-increases heart rate cause it prevents hyperpolarization of heart muscle that is required for a slow heart rate.

-inhibits digestion which should be occuring in the parasympathetic response

Acetylcholine (ACh)

A neurotransmitter that enables learning and memory and also triggers muscle contraction. Involved at nicotnic and muscarinic junctions

Is potato and tomato in the same genus?

Yes, they are in the same genus. Potato is Solanum tuberosum and tomato is Solanum lycopersicum.

Describe the effect of light on the toxicity of potato

when light hits the potato, it green because it is producing cholrophyll and sprouts since it is trying to grow a new plant. This process however releases a lot of toxins and therefore green or sprouted tubers of potato should never be consumed. toxins that they create are called glycoalkaloids.

what are the parts of the potato plant that makes abundant glycoalkaloid toxins? List them from high to low

For the plant: Flowers, sprouts, leaves

If you just look at the tuber in isolation: Peel, skin, flesh

what exactly are the toxins that the potato produces?

•Glycoalkaloids:

α-solanine & α-chaconine

•synergistic

•cell lysis (membrane disruption)

•inhibits acetylcholinesterase

which is involved in hydrolyzing acetylcholine.

gastrointestinal discomfort

•rapid & weak pulse, breathing

Herbivore defense

α-solanine and α-chaconine structure

this was the best image I could add using free quizlet. Both of these molecules basically have an indolizidine ring, steroid molecule, and then three monosacchardies connected with glycosidic linkages

what are the toxic effects of solanine glycoalkaloids?

-all the effects of a typical glycoalkaloid

-inhibits cholinesterase

-disrupt cell memebranes (likely because of its cholesterol structure)

-cause birth defects

-cause apoptosis by affecting mitochondrial membranes and relasing so much caclium into the cell that apoptosis is triggered.

what are the toxic effects of chaconine glycoalkaloids?

-all the effects of a typical glycoalkaloid

-natural toxicant that produces a bitter taste

-produced in response to stress and has insecticidal and fungicidal properties.

What are the five major categories of toxins/irritants that affect the skin?

1. Raphide oxalates

2. Stinging hairs

3. Chemical irritants

4. Phototoxins

5. Allergens

Structure of the Skin

epidermis, dermis, hypodermis(fat layer or subcutaneous layer)

What families are raphide oxalates associated with? What are the raphides made of?

Araceae

Polygonaceae (buckwheat family)

They are made of calcium oxalate.

Name some plants in the Araceae family

Wide variety of attractive house plants are involved in this family.

Peace Lily (Spathiphyllum)

Dumb Cane (Dieffenbachia)

syn pothos (Epipremnum)

Monstera

Philodendron

Elephant Ears, Taro (Colocasia)

What are the benfits of calcium oxalate crystals in plant cells?

-pH balance

-defense against herbivores (immediate stinging and edema)

-remove excess oxalic acid