What is the structure of fatty acids?

They are long unbranched chains of carbon atoms which are bound to hydrogen

Unsaturated fatty acids have ________

double bounds

monounsaturated (MUFA) has ____________

one carbon carbon double bond

polyunsaturated (PUFA) has _________

two or more double carbon

Where is unsaturated fatty acids found?

In vegetables oils, avocados, sunflower oil, walnuts, flax, canola oil and fish oil

Saturated fatty acids are _______ at room temperature

solid

Unsaturated fatty acids are _________ at room temperature

liquid

What is the melting point for saturated fatty acids?

relatively high

What is the melting point for unsaturated fatty acids?

relatively low

What is the source for saturated fatty acids?

animal fats, palm and coconut oil

What is the source for unsaturated fatty acids?

plant and vegetable oil, fish oil

What are the two essential fatty acids that your body cannot synthesized an must be obtained from food?

linoleic and aplha-liolenic

The basic fats are used to build _____________

specialized fats omega-3 and omega-6

The location of where the double bond is affects the ____________

naming of the fatty acids.

Omega-6 has a double carbon at the _________

sixth carbon

Omega-3 has a double carbon at the ___________

third carbon

Alpha-linolenic acid (ALA)

Eicosapentaenoic acid (EPA)

Docosahexaenoic (DHA)

are all _________

omega-3s

what does 18:3n-3 mean?

its has 18 carbons, 3 double carbon at (n-3) carbon

What is the scientific abbreviations for Eicosapentaenoic acid (EPA)

20:5n-3

What is the scientific abbreviations for Docosahexaenoic (DHA)?

22:6n-3

What is the scientific abbreviations for Alpha-linolenic acid (ALA)?

18:3n-3

EPA and DHA are considered to be derived from?

fishes cause that is where they are abundant

ALA is considered to be derived from?

plants

Omega-6s are precursors for _____________?

prostaglandins

What is prostaglandin, and what is its function?

they are a group of lipid compounds that are derived from fatty acids. they also play a role in the formation of blood clots and in the induction of labor. Also known for regulating the contraction and relaxation of smooth muscle tissue, controlling inflammation, and regulating blood flow.

What happens when you take aspirin and nonsteroidals ?

They block the synthesis of prostaglandin

What are the major sources of omega-6s?

vegatable oils, sunflower, safflower, and corn oil, meat, eggs and dairy

What can deficiency of omega-3's and omega-6 lead to?

failure to grow, alopecia, dermatitis

What happens when you consume more omega-6 then omega 3?

They compete with the omega-3 enzymes. So fewer enzyme are used to convert the omega-3 fats into anti-inflammatory chemical.

Glucose provides the ______?

primary substrate for lipogenesis

What is De novo synthesis?

It is the making of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation

Where does De novo synthesis occur?

In the cytosol liver, kidney, brain, lung, mammary glands and adipose tissues

How does fatty acid synthesis occur?

By combining eight two-carbon fragments to form a 16 carbon saturated acid

What is palmitate?

It is a 16-carbon saturated fatty acid, which is the major fatty acid found in palm oil.

Precursors for Fatty acid synthesis

Acetyl CoA, ATP, NADPH and CO2

Where are the sites of Fatty Acid synthesis?

Major:
-Liver
-Lactating Mammary Gland

Minor:
-Adipose Tissue
-Kidney

Where in the cell does FA synthesis take place?

Cytosol

first stage of fatty acid synthesis

when acetyl CoA is transferred out of the mitochondria and into the cytoplasm. citrate is also transported into the cytoplasm and it gets cleaved into oxaloacetate and acetyl CoA

second stage of fatty acid synthesis

acetyl CoA is activated to form malonyl CoA

third stage of fatty acid synthesis

there is repetitive addition and reduction of two carbon units to synthesize C16 fatty acids. this occurs on an acyl carrier protein, a molecular scaffold

how does citrate generate acetyl CoA?

it is transported into the cytoplasm and cleaved by ATP-citrate lyase to make acetyl CoA.

What is the major oxidation of fatty acids?

Mitochondrial beta

What is the minor oxidation of fatty acids?

alpha, omega and perxisomal beta

What happens during fasting to fatty acids?

They become the predominant substrate for energy production via oxidation in the liver, cardiac and skeletal muscle

How does mitochondrial beta oxidation occur in the liver?

acetyl-Coa is converted into ketone bodies

How does mitochondrial beta oxidation occur in the skeletal and cardiac muscle?

acetyl-Coa is completely oxidized in the tricarboxylic acid (TCA) pathway ultimately to CO2 and H2O

How many steps is the mitochondrial beta oxidation?

20 steps

how are fatty acids released?

By Insulin regulated lipase from stored triglyceride

Which cells are fatty acids carried by?

By albumin

How is fatty acyl CoA transported into the cell mitochondria?

Via the Carnitine Shuttle

What is mitochondrial beta oxidation?

catabolic pathway where fatty acids are broken down in mitochondria to produce acetyl-CoA

What is the first step in mitochondrial beta oxidation?

first oxidation
single c-c bond to a c=c bond.
reduction of FAD

What is the second step in mitochondrial beta oxidation?

hydration of the double bond between a and b carbon into a hydroxyl group

What is the third step in mitochondrial beta oxidation?

second oxidation
oxidation of the b carbon
hydroxyl group into a carbonyl group
Reduction of NAD

What is the fourth step in mitochondrial beta oxidation?

thiolytic cleavage that produces acyl-CoA and acetyl-CoA (2Cs) is released
Coenzyme A is linked to the new Acyl- CoA (14C)

FA are _________________ compared to glucose

highly reduced
(Can get more ATP out of a highly reduced molecule)

Alpha α- oxidation- Predominantly takes place in _____________

brain and liver, one carbon is lost in the form of CO2.

What is the substrate of α- oxidation?

Phytanic acids which is present in milk or derived from the phytol present in chlorophyll and animal fat

What does α- oxidation produce?

No ATP

Where does α- oxidation occur?

In the methyl group at the beta-carbons which blocks beta oxidation

peroxisome β-oxidation mainly happened in _________

mitochondria, but can also occur at peroxisome.

the oxidation in peroxisome occurs on ________________

very long fatty acids. For full oxidation to CO2 and H2O and NAD+

What is formed after peroxisome β-oxidation?

Formation of DHA

What are the two groups of inborn errors of metabolism?

They are acute sever manifestation and chronic progressive

Zellweger syndrome ___________

people with this syndrome cannot produce peroxisomes and therefore cannot oxidize such fatty acids.

X-linked adrenoleukodystrophy (XALD) ____________

peroxisomes cannot oxidize very long chains due to lucking functional transporter from them

What is the most common type of Fatty Acid Oxidation Disorders?

Medium chain acyl CoA dehydrogenase deficiency (MCADD)

Most Fatty Acid Oxidation Disorders are _________

Inherited

What is the treatment for Fatty Acid Oxidation Disorders?

Avoid fasting, some patients may require low fat diets

What is hyperammonemia?

is a metabolic condition characterized by the raised levels of ammonia, a nitrogen-containing compound.

What is hyperuricemia?

is when you have too much uric acid in your blood.

Acylcarnitine analysis is

helpful in the evaluation of hypoglycemia, hypotonia, cardiomyopathy, rhabdomyolysis, and metabolic acidosis

Acylcarnitine analysis is commonly performed by _______________

MS/MS directly after derivatization to either butyl or methyl esters.

A plasma acylcarnitine profile can aid in the diagnosis of _____________

organic acidemas in addition to fatty acid oxidation disorders (FAODs)

Plasma is the preferred sample type for ______________

acylcarnitine analysis

Peroxisomes are cell organelles which are found in all human cells except _________

Erythrocytes

Peroxisomes posses both _____________

Catabolic and anabolic functions.

Peroxisomes are considered to be ____________

"helpless" organelles because they very much rely on the interaction with other subcellular organelles especially mitochondria.

Neonatal adrenoleukodystrophy

Most present with early infantile hypotonia & seizures

Similar findings can be seen in the isolated deficiency of peroxisomal straight-chain acyl-CoA oxidase

Disorder of peroxisome biogenesis due to mutated PEX

Zellweger syndrome spectrum
- zellweger syndrome
- neonatal adrenoleukodystrophy
- infantile refsum disease

Rhizomelic chondrodysplasia punctata

Rhizomelic Chondrodysplasia Punctata Type 1

marked reduction of plasmalogen levels and impairment of plasmalogen synthesis

increased levels of phytanic acid, impaired ability to oxidize

Zellweger syndrome symptoms

dysmorphic face, eye abnormalities, severe weakness and hypotonia, neonatal seizures, renal cortical cysts, hepatomegaly and impaired liver function, severe psychomotor retardation

Zellweger syndrome life span

autosomal recessive
most common in childhood
apparent at birth - death by 1-2yo

Neonatal adrenoleukodystrophy symptoms

Developmental delay, neuromigration defect, hearing loss, vision impairment, liver dysfunction,

What is elevated in the Zellweger syndrome when diagnosing in plasma assay?

Very long fatty acid chain

phytanic, peristanic, pipecolic acid

What is decreased in the Zellweger syndrome when diagnosing in red cell membrane assay?

plasmalogens

What is PEX1?

It is the gene associated with the Zellweger syndrome occurs in about 68% of individuals

RHIZOMELIC CHONDRODYSPLASIA PUNCTATA (type 1) defect is in ________

PEX 7 gene = PTS2 receptor; AUTOSOMAL RECESSIVE

Rhizomelic Chondrodysplasia Punctata Type 1 health problems

The health problems are severe and apparent either at birth or in early infancy. Some children will reach childhood but it is rare that they make it past the first decade.

Rhizomelic Chondrodysplasia Punctata Type 1 symptoms

The major features that are noticed with these patients are the skeletal abnormalities, distinctive facial features, ID, and respiratory problems.

What is elevated in Rhizomelic Chondrodysplasia Punctata?

Plasma phytanic acid

What is defected in Rhizomelic Chondrodysplasia Punctata?

Red cell plasmalogens

Rhizomelic Chondrodysplasia Punctata defect is in __________

The PEX7 receptor. It is autosomal recessive

Adrenoleukodystrophy (ALD)

insufficiency of a persons adrenal glands and growth of myelin

Three phenotypes of ALD

1. Cerebral ALD- most devastating
2. Adrenomyeloneuropathy- most common
3. Adrenal insufficiency

What are the signs and symptoms childhood Cerebral form (CCALD)

Affects children between 3-10
Mistaken for learning disability
Seizures, hyperpigmentation, vision loss

How do you diagnoses for childhood Cerebral form (CCALD)?

Brain MRI is always abnormal in neuralgically symptomatic males.

What are the signs and symptoms childhood Cerebral form (Adrenomyeloneuropathy)

Affects all men and some women in 40s
Average age is 28
Caused by slow and progressive damage to myelin and axons due to VLCFA accumulation
Stiffness/tingling in legs, incontinence, cerebellar disorders (coordination/balance issues), sexual dysfunction and impaired adrenocortical function

What are the signs and symptoms childhood Cerebral form (Adrenal Insufficiency)

Cells that produce hormones are damaged and cause... weakness/fatigue, nausea, low bp, hyperpigmentation

What is elevate in x-linked Adrenomyeloneuropathy?

abnormally elevated very long-chain fatty acids (VLCFAs)

What is the gene defected in x- linked Adrenomyeloneuropathy?

is s a gene called ABCD1.

What is the treatment for x- linked Adrenomyeloneuropathy?

Supportive symptomatic such as steroid treatment.

Hemopoietic stem cell transplantation (HSCT) may

Presymptomatic treatment for x- linked Adrenomyeloneuropathy?

Newborn screening program including CA to screen X-ALD