What is the main mineral in teeth? formed during mineralization - calcium, phosphate, and hydroxide ions combine to form it

Hydroxyapatite: Ca10(PO4)6(OH)2; a dimer and highly insoluble

Final Exam Flashcards by Rabera Ondieki

Outer to inner layers

Thick Peptidoglycan Cell Wall (This gets stained Purple by Gram Stains)
Periplasmic Space
Plasma Membrane

Gram Positive

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Outer to inner layers

Outer Membrane (Lipopolysaccharide and Protein)
Periplasmic Space
Thin Peptidoglycan Cell Wall
Plasma Membrane

Gram Negative

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This causes caries by dissolving the enamel and dentin

Lactate

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People who keep their teeth clean and have no periodontal diseases have more XXXX facultative anaerobes in their mouth.

Gram Positive

Thick wall of Gram +ve bacteria allows them to tolerate the low pH caused by lactate.

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These agents are used to stop hemorrhage from inflamed pulp and injured gingiva

Hemostatic agents

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These hemostatic agents shrink or constrict tissues

astringents

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What are the best Dental Astringents:

zinc, Iron, and Aluminum salts

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This astringent is Common in gingival retraction because of its astringent abilities
Can precipitate protein, constrict blood vessels, and extract fluid from tissues. Highly soluble in water

Aluminium Chloride

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This astringent on an open wound results in agglutination of surface proteins leading to quick and efficient hemostasis

Ferric Subsulfate solution (Monsel’s solution)

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Which coagulation pathway is this?

triggered when blood comes into physical contact with abnormal vessel wall (e.g from infection, bacteria in blood vessel, anything unusual)
Factor XII, XI, & IX becomes active which triggers factor X activation leading to the final common pathway

Intrinsic Pathway

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Which coagulation pathway is this?

initiated by factors released from injured tissues (tissue factors) into the blood
Factor VII becomes activated which triggers factor X to be activated as well leading to the final common pathway

Extrinsic Pathway

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Final coagulation common pathway in chronological order

Prothrombin (II) → Thrombin (II_a) (Pro- Before)
Fibrinogen (I) → Fibrin (I_a) (gen- Genesis> It makes Fibrin)
XIII_a aids form to cross-linked fibrin clot

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This protein is found in: Hair, wool, skin, horns and fingernails; composed of α-helical polypeptides

Keratin

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What type of keratin is this? these type of areas: outer surface of hard palate and gingival mucosa

Parakeratinized areas

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What type of keratin is this? cheeks, lips, ventral surface of tongue, soft palate; allows permeability of small fluids and molecules

Nonkeratinized regions:

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What type of collagen is this?

formed in the intracellular matrix
selected hydrolysine residues are glycosylated with glucose and galactose

Procollagen

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What type of collagen is this?

It is formed in the extracellular matrix
secreted by a golgi vacuole into the extracellular matrix
the n-terminal and c-terminal are cleaved by peptidases

tropocollagen

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This is not included in the synthesis of enamel

Collagen
ameloblasts
enamelin
amelogenin

Collagen

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What is the composition of ? 33% Glycine; ~30% Proline and Hydroxyproline

Collagen

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Which collagen oral disorder is this? fragile bones

33% Glycine; ~30% Proline and Hydroxyproline

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Which collagen oral disorder is this? opalescent or completely missing teeth

Detinogenesis imperfecta:

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Ascorbate cannot be made by humans as we lack L-gulonolactone oxidase
Protects macromolecules from oxidative damage by neutralizing ROS
Antioxidant property is more important extracellularly
Deficiency leads to periodontal disease (scurvy)
- Loss of gingival and periodontal membrane fibers → loosening of teeth
- Periodontal membrane fibers are removed but not replaced → slow turnover of collagen in bone

Ascorbate (vitamin C) is important in the hydroxylation (proline and lysine) of collagen

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What is the main mineral in teeth?
formed during mineralization - calcium, phosphate, and hydroxide ions combine to form it

Hydroxyapatite: Ca₁₀(PO₄)₆(OH)₂; a dimer and highly insoluble

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What are the hard tissues in the tooth?

Enamel

Dentin

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What tissue formation is described below? * Formed in the extracellular matrix with _amelogenins_ and _enamelins_ (both are proteins) as building blocks * ***Ameloblasts*** secretes _amelogenins_ and _enamelins_; present only during development

Enamel formation

What tissue formation is described below? Formed around the pulp on an extracellular matrix of collagen and non-collagenous proteins secreted by ***odontoblasts***

Dentin formation

This process includes the following: * Scaffolding proteins (“rebars of teeth production”): collagen, amelogenins * High concentration of ions: calcium, phosphate * Process called *nucleation* * *calcium, phosphate, and hydroxide ions combine to form solid hydroxyapatite*

Mineralization

* What happens to the enamel at pH 5.5 * Protons diffuse into hydroxyapatite crystal to react with OH group to change the crystal into an amorphous calcium monohydrogen phosphate solid that slowly dissolves. * Ca10 (PO4)6 (OH)2 -\> CaHPO4 * Acids lower pH and strip Calcium and Phosphate off from tooth

Demineralization

These cells mineralize dentin in the presence of many factors on a scaffolding protein called collagen

Odontoblasts

These cells mineralize enamel in the presence of protein factors including a scaffolding protein class called amelogenins

Ameloblasts

This part of the tooth mineralizes towards the pulp

dentin

This part of the tooth mineralizes towards the crown and loses ameloblasts

enamel

In the oral cavity, what do bacteria metabolize aerobically?

CO2 and H2O

In the oral cavity, what do bacteria metabolize anaerobically?

lactic acid - we do not want this

* Made by ameloblasts * Only calcified tissue that does NOT contain collagen * 97% by weight mineral (hardest substance in the body) * Less than 1% by weight protein

Enamel

* Made by odontoblasts * Calcified over type 1 collagen fibers like bone * 70% mineral * 30% protein

Dentin

* Primary function is to form dentin (by the odontoblasts)

Pulp

Which genetic structure is this? * Polymer of deoxyribonucleoside monophosphates linked by 3’⇢5’ phosphodiester bonds * consists of two strands, arranged in a double helix. These strands are made up of subunits called nucleotides. Each nucleotide contains a phosphate, a 5-carbon sugar molecule and a nitrogenous base.

DNA

Which genetic structure is this? Single stranded helix * Ribonucleotides joined by phosphodiester bonds * ribose sugar * 3 classes 1. mRNA 2. rRNA 3. tRNA

RNA

* Begins at a site called the origin of replication by DnaA protein (Mainly A-T base pairs) * DNA Helicase unwinds the double helix while ssDNA-binding proteins keep the strands apart and protect DNA from nucleases * Primase adds an RNA primer with a free OH on the 3’ end * DNA Pol III synthesizes in 5’ -\> 3’ direction with leading and lagging strands until it reaches proximity to an RNA primer * Topoisomerase I (Cuts 1 strand) and Topoisomerase II (Cuts both strands) removes supercoils. Example. * RNA primer is excised and gap filled by DNA Pol I * DNA Ligase links the final phosphodiester linkage of DNA chain synthesized by DNA pol III with the chain made by DNA Pol I

DNA replication in prokaryotes

Which enzyme unwinds the double helix in DNA replication of prokaryotes?

DNA Helicase

what keeps the SNA strands apart and protects DNA from nucleases?

Single Stranded DNA binding proteins

This enzyme adds an RNA primer with a free OH on the 3' end

Primase

This DNA polymerase synthesizes in 5’ -\> 3’ direction with leading and lagging strands until it reaches proximity to an RNA primer

DNA Pol III

This enzyme cuts 1 strand of DNA during **DNA Replication in prokaryotes**

Topoisomerase I

This enzyme cuts both DNA strands and removes supercoils during DNA replication in prokaryotes

Topoisomerase II (Cuts both strands) removes supercoils

During DNA replication in prokaryotes, XXXX is excised and the gap is filled with XXXX

RNA Primer, DNA Pol I

This enzyme links the final phosphodiester linkage of DNA chain synthesized by DNA pol III with the chain made by DNA Pol I

DNA ligase

* RNA Polymerase attaches to TATAA Box (TATAAT sequence) (Doesn’t require primer) * Proceeds along DNA anti-sense strand with RNA growing 5’ -\> 3’ direction * Rho-independent termination - Generates sequence of self-complementary bases that causes it to fold on itself forming a hairpin loop. This facilitates separation of RNA from DNA * Rho-dependent termination - Rho uses its ATP-dependent helicase activity to separate RNA from DNA * RNA is used as unaltered primary transcript as soon as it is made. (Prokaryotes will often begin translation as transcription is taking place as they don’t have a nucleus to separate them)

This is the **Transcription in Prokaryotes process**

This type of termination in the transcription process in prokaryotes generates sequence of self-complementary bases that causes it to fold on itself forming a hairpin loop. This facilitates separation of RNA from DNA

Rho-independent termination

During this type of termination in the transcription process of prokaryotes, Rho uses its ATP-dependent helicase activity to separate RNA from DNA

* Rho-dependent termination

T/F RNA is used as unaltered primary transcript as soon as it is made. (Prokaryotes will often begin translation as transcription is taking place as they don’t have a nucleus to separate them)

True

T/F ## Footnote RNA Polymerase attaches to TATAA Box (TATAAT sequence) (Doesn’t require primer)

True

T/F During transcription in prokaryotes, the process proceeds along DNA anti-sense strand with RNA growing 5’ -\> 3’ direction

True

RNA primers during DNA replication in eukaryotes are removed by? * DNA Pol I * RNase * DNA Pol III * DNA Ligase

RNase

T/F DNA replication in prokaryotes has multiple origins of replication because it has larger DNA

F; DNA replication in prokaryotes has one origin of replication because it has small DNA, Eukaryotes have multiple origins of replication because they have large DNA

What happens in transcription of eukaryotes? 1. Similar to prokaryotes except it involves separate polymerases along with transcription factors 2. Undergoes modification of RNA through capping at 5’ end, addition of Poly(A) tail at 3’ end, and removal of introns 3. RNA Polymerase attaches to TATAA Box (TATAAT sequence) (Doesn’t require primer) 4. 1&3 5. All the above

1. Similar to prokaryotes except it involves separate polymerases along with transcription factors 2. Undergoes modification of RNA through capping at 5’ end, addition of Poly(A) tail at 3’ end, and removal of introns

* DNA polymerase that Elongates okazaki fragments of lagging strand

DNA Pol 𝛿 (delta)

DNA polymerase that Elongates the leading strand

DNA Pol ɛ (epsilon)

* DNA polymerase that Synthesizes rRNA (rRNA is 80% of RNA in cell)

RNA Pol I

DNA polymerase that Synthesized mRNA

RNA Pol II -

DNA polymerase that - synthesized tRNA and 5S rRNA

RNA Pol III

Which type of mutation is this? One amino acid is swapped for another. _(Effects on RNA)_ Purine with Purine or Pyrimidine with Pyrimidine. (A\>G)

Transition

Which type of mutation is this? One amino acid is swapped for another. _(Effects on RNA)_ Purine with Pyrimidine or the other way. (A\>T/U)

Transversion

Substitution can lead to 3 different types of mutations. _(Effects on Protein)_ * No change to Protein because some Codons are redundant.

Silent Mutation

Substitution can lead to 3 different types of mutations. _(Effects on Protein)_ * Different Amino Acid. (This protein might still work if the change was to a similar size and type of AA)

Missense Mutation

Substitution can lead to 3 different types of mutations. _(Effects on Protein)_ * Forms a Stop codon. (This protein will most likely not work at all)

Nonsense Mutation

DNA mutation where an insertion or deletion happens leading to huge changes in the reading frame. This protein is also going to be garbage as every codon after the mutation will be ruined)

Frameshift mutation

DNA Damage can be caused by the following

1. Hydrolysis 2. Oxidation 3. Methylation 4. UV Light: 1. Forms Pyrimidine Dimers (THYMINE) 5. Ionizing Radiation: 1. Damages DNA Directly 2. Forms _Strand Breaks_ in the Double Helix.

DNA damage that Forms Pyrimidine Dimers (THYMINE)

UV Light

DNA damage that causes 1. Damages DNA Directly 2. Forms _Strand Breaks_ in the Double Helix.

Ionizing Radiation

Which type of DNA repair disease is this? * Pyrimidine dimers formed in skin cells exposed to UV light * Defects in excision repair due to mutant UV specific endonuclease

Xeroderma pigmentosum

Which type of DNA repair disease is this? * Defects in excision repairs * Neurodegenerative disease * Poor coordination

Ataxia Telangiectasia

Which type of biotechnology is this? separate macromolecules based on charges and size (Gel separates the size and Electricity separates by charge)

Gel Electrophoresis

Which type of biotechnology is this? detect specific proteins.

Western Blotting

Which type of biotechnology is this? detects specific DNA sequences

Southern Blotting

Which type of biotechnology is this? detects specific RNA sequences

Northern Blotting

Which type of biotechnology is this? amplify small samples of DNA

polymerase chain reaction (PCR)

Which type of biotechnology is this? separate components of mixture via columns

High Performance Liquid Chromatography (HPCL)

Which type of biotechnology is this? determine molecular 3D structures

X-ray Crystallography and Nuclear Magnetic Resonance

Which type of biotechnology is this? ## Footnote - determine amino acid sequence of peptide

Edman Degradation

Which type of biotechnology is this? determine amino acid sequence of peptide

Mass Spectrometry (more modern)

_SNOW DROP mnemonic_ Southern blot Northern blot O Western blot

DNA RNA O Protein

Start Codon is AUG and codes for

Methionine

* Stop Codons are

* Stop Codons are UAG, UAA, UGA.

* Generic code is XXX or XXX. eg: Valine is coded by GUU, GUC, GUA and GUG. * This means the third AA is allowed to be anything and it will still code for the same thing (Called a silent mutation!)

**protein that provides structural support for a chromosome**

histone ## Footnote Each chromosome contains a long molecule of DNA, which must fit into the cell nucleus. To do that, the DNA wraps around complexes of histone proteins, giving the chromosome a more compact shape

* Eukaryotic DNA is packaged with histones into nucleosomes which also pack into chromosomes. * DNA\> Nucleosome beads (Histone core + DNA) \> Chromosomes

Histones

* Nucleosomes are made up of 4 types of histones (2 of teach per nucleosome)

* H2A, H2B, H3, H4 * H1 is also there but he hangs out outside of nucleosome cores.

* _General components_: central chiral carbon, amino group, carboxyl group, r-group * Exceptions: glycine with 2 hydrogen groups

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arginine, lysine, histidine (HAL)

_Basic amino acids_:

glutamate, aspartate (ates)

_Acidic amino acids_:

_Sulfur-containing amino acids_:

methionine, cystine

contains a secondary amino because its R-group loops back and connects to the backbone

_Proline_:

* R-group is hydrogen so it is not a chiral carbon.

_Glycine_:

Which type of amino acids cannot be created by our bodies, so we need to take them in from our diet

Essential amino acids

Non Essential Amino Acids ACGT PS

* List to memorize (non-essential) ACGT PS * Alanine, Asparagine, Aspartate, Arginine (only essential in infants) * Cystine * Glycine, Glutamine, Glutamate * Serine * Proline * Tyrosine

**Protonated or Deprotonated: pH in relation to pKa** * pH\>pKa :

Deprotonated

**Protonated or Deprotonated: pH in relation to pKa** * pH

Protonated

This is the composition of which protein? * 1) ⅓ Glycine * 2) 30% Proline and 4-Hydroxyproline * 3) 3-hydroxyproline and 5 hydroxylysine in small amounts. * Hydroxyproline and hydroxylysine are not present in other proteins and can be used to identify this protein

Collagen

Which type of protein : composes 90% of human collagen; found in teeth, bone, skin, and tendons

Type 1 Collagen

Which are the structural/fibrous proteins? 1. Collagen 2. Keratin 3. Elastin 4. Hemoglobin

1. Collagen 2. Keratin 3. Elastin

what are the globular/functional proteins? 1. Hemoglobin 2. Myoglobin 3. Collagen 4. Keratin 5. Elastin

1. Hemoglobin 2. Myoglobin

Which globular protein is this? * Binds oxygen _reversibly_. 4 subunits. Each subunit has alpha helices structure + heme binding pocket similar to myoglobin. Can bind 4 O2 molecules at a time. * Found in RBC, the main function is to transport O2 from the lungs to the capillaries of tissues. * Transport H+ and CO2 from tissues to lungs * 2 alphas and 2 betas held together non-covalently * Deoxygenated = T taut state * Oxygenated = R relax state * Sigmoidal Bohr Curve due to cooperative binding.

Hemoglobin

Which globular protein is this? * Binds oxygen reversibly. Only binds a 1 O2 molecule at a time. * Higher affinity to oxygen than normal Hemoglobin (To allow transfer, esp in muscle) * Found mainly in heart and skeletal muscle * Acts as a reservoir for oxygen * Hyperbolic Bohr curve.

Myoglobin

Binding affinity for O2 increases/decreases due to ligand binding

Bohr effect

T/F The Bohr Effect decreases affinity, right shift, increase in protons: H+, 2,3-BPG, CO2

* _Peptide bonds_ link A.A’s together, linear, _trans-bond_ to avoid steric hindrance.

Primary protein structure

* _Hydrogen bond_s formed between carbonyl and amino groups.

Secondary protein structure

* R groups form _hydrogen, disulfide, ionic interactions, and hydrophobic interactions._

Tertiary protein structure

* bonded by _multiple polypeptide chains_ through many interactions (non covalent)= hydrophobic interactions, H-bonds, ionic bonds.

Quaternary protein structure

**Protein Misfolding Diseases** * accumulation of insoluble, spontaneously aggregating misfolded proteins consisting of β-pleated sheets * Ex: Alzheimer, Parkinson

_Amyloid diseases_:

**Protein Misfolding Diseases** * caused by a _protein (PrP)_. 1. Creutzfeldt Jakob disease (humans) 2. Scrapie (sheep) 3. Bovine spongiform encephalopathy (Mad cow disease)

_Prion diseases_:

**Enzyme Inhibition on K_m and V_max** * Km increases and Vmax stays the same.

_Competitive inhibitor_:

**Enzyme Inhibition on K_m and V_max** * Km is unaffected (because the substrate binds to a different site) and Vmax decreases.

_Noncompetitive inhibitor_:

**Electron Transport Chain Complexes** * this transmembrane protein serves as the offloading site where NADH dumps off its electrons. This complex pumps 4 electrons per NADH offloaded.

_Complex I_:

**Electron Transport Chain Complexes** ## Footnote also known as succinate dehydrogenase, this peripheral protein (not a proton pump) also plays a key role in the Krebs Cycle through generating FADH₂ and providing it directly to the ETC.

_Complex II_:

**Electron Transport Chain Complexes** * after it receives its electrons from complexes I or II, this complex pumps 4 protons into the intermembrane space.

_Complex III_:

**Electron Transport Chain Complexes** * this complex reduces oxygen into water as a way to cycle the electrons out of the ETC. This complex pumps 2 protons per cycle.

_Complex IV_:

**Electron Transport Chain Complexes** also known as ATP synthase, this structure utilizes the energy released from the proton gradient created in complexes I through IV to create ATP.

_Complex V_:

* Carrier proteins in the ETC that allow the protons to go from the inner membrane space to the mitochondrial matrix without being captured as ATP. It does not re-enter via complex V

**Protein Uncouplers:**

Enzymes that hydrolyze glycosidic bonds to form monosaccharides

*Glycosidases*

* Digestion starts in the mouth where salivary XXX starts hydrolyzing random 𝛂(1-4) bonds if polysaccharide chains * Carbohydrates digestion is halted in the stomach temporarily where the acidity inactivates XXX * After the acidic stomach contents are neutralized by bicarbonate in the small intestine, pancreatic 𝛂-amylase continues the process of starch digestion * End products: glucose, galactose, fructose (monosaccharides)

salivary 𝛂-amylase

**Forms of Polysaccharides** _Plants_: (straight chain)

amylose

**Forms of Polysaccharides** _Plants_: (branched chain)

amylopectin

**Forms of Polysaccharides** * _Animals_: It is branched and made out of a-1,4 and a-1,6, but mostly a-1,4.

glycogen

* Humans cannot digest cellulose because we lack the enzyme which helps hydrolyze the beta (1-4) glycosidic bonds that cellulose has.

endoglycosidase

Pathway: * Abundant in pancreatic beta cells, liver, and kidney. * Glucose and fructose leave through GLUT2 in the small intestinal cells (enterocytes).

GLUT2

Pathway * Abundant in adipose tissue and skeletal muscle. * Insulin dependent. * The receptor is found inside of the cell and not on the surface like the others.

GLUT4

**Sugar Movement In and Out of Enterocytes**

**Glucose** Enter: SGLT-1: Cotransport with Na+ gradient Exit: GLUT-2 **Galactose** Enter:SGLT-1: Cotransport with Na+ gradient Exit: GLUT-2 **Fructose** Enter: GLUT-5 Exit GLUT-2

T/F If you have no Na+ gradient. SGLT will not be able to transport Glucose and Galactose.

Which enzyme deficiency is this? * Unable to breakdown lactose (galactose + glucose) * Asians and African Americans(Not people from Africa though??) are lactase deficient.

Lactase deficiency

How much Gross ATP is generated during glycolysis:

4 ATP

How much Net ATP is generated during glycolysis

2 ATPs

**Important Glycolysis Steps** * _Irreversible steps_: starred in red * _ATP produced_: starred in blue * _ATP used_: starred in orange

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What enzyme catalyzes the rate-limiting step of glycolysis (Also known as the _Committed_ Step)

PFK-1

* Up-regulators of PFK1 are

AMP and fructose 2,6- bisphosphate

Down regulators of PFK-1 are

Citrate and ATP

* Which enzyme is responsible for splitting Fructose 1,6 bisophophate (6C) into DHAP and G3P (2 x 3C)

Aldolase

Which enzyme is able to be inhibited by fluoride, this enzyme is responsible for transforming 2-phosphoglycerate (2PG) to phosphoenolpyruvate (PEP)

Enolase

Which enzyme_:_ interconverts DHAP and G3P (G3P continues down glycolysis)

_Triose phosphate isomerase_

* Aerobic metabolism * Pyruvate → oxaloacetate via?

pyruvate carboxylase (enters Krebs cycle)

* Aerobic metabolism * Pyruvate → acetyl CoA via?

pyruvate dehydrogenase (enters Krebs cycle)

* Anaerobic metabolism * Pyruvate → lactate via XXX (occurs in erythrocytes, exercising muscles, anoxic tissues) * Can result in lactic acidosis

lactate dehydrogenase

* Anaerobic metabolism * Pyruvate → ethanol via XXX and then alcohol dehydrogenase (occurs in yeast and other microorganisms)

pyruvate decarboxylase

**Pyruvate Dehydrogenase Complex Subunits and Coenzymes** E1

Thiamine Pyrophosphate (TPP)

**Pyruvate Dehydrogenase Complex Subunits and Coenzymes** E2

Lipoic acid and CoA

**Pyruvate Dehydrogenase Complex Subunits and Coenzymes** E3

FAD and NAD+

T/F Hexokinase has a higher V_max, which makes it better able to deal with this onslaught

F because, Glucokinase has a higher V_max, which makes it better able to deal with this onslaught

T/F glucokinase exists primarily in the liver, which experiences a much stronger rush of glucose after a meal is consumed when compared to the rest of the body

The process of making glucose (sugar) from its own breakdown products or from the breakdown products of lipids (fats) or proteins. This occurs mainly in cells of the liver or kidney.

Gluconeogenesis

What are the irreversible steps in glucogenesis?

_Irreversible steps_: pyruvate → oxaloacetate, oxaloacetate → PEP, glucose-6-phosphate → glucose, fructose-1,6-bisphosphate → fructose 6 phosphate

Which enzyme during gluconeogenesis does this occur? * Catalyzes glucose-6-phosphate → glucose * Found only in liver + kidney

_Glucose-6-phosphatase_: (function and location)

Glucogenesis can occur with different substrates. Why doesn’t gluconeogenesis occur in adipose tissue (where TAGs are made)?

* Because adipocytes LACK GLYCEROL KINASE. Once glycerol is delivered by the blood into the liver, glycerol kinase metabolizes glycerol → G3P to undergo gluconeogenesis to make glucose

Glucogenesis can occur with different substrates. lactate(carbohydrates) undergo the XXX

Cori Cycle

Which cycle is this? Lactate is released into the blood by exercising skeletal muscle and by cells that lack mitochondria (such as erythrocytes), then taken up by the liver in order to make glucose

Cori Cycle ![]()

T/F During these steps NADH is produced, 1. isocitrate to alpha-ketoglutarate (via isocitrate dehydrogenase) 2. alpha-ketoglutarate to succinyl-CoA (via alpha-ketoglutarate dehydrogenase) 3. malate to oxaloacetate (via malate dehydrogenase)

True

T/F During this steps during the citric acid cycle, FADH2 is produced succinate to fumarate (via succinate dehydrogenase complex - complex II

True

* This occurs in the cytosol * Uses Glucose-6- Phosphate from glycolysis to generate many important sugars. Notable Products: * NADPH: Used in reductive Anabolic Pathways * Ribose 5-Phosphate: Nucleic Acid Synthesis * G3P and F6P Glycolysis (You don’t really have to know this but it’s nice to know)

**Pentose Phosphate Pathway**

The enzymes generate NADPH + H from NADP.

Glucose-6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase

* _NADPH_: provides the reductive energy for this process through donating its electrons to the glutathione pool * _Glutathione_: this protein is reduced and ultimately reduces reactive oxygen species into water

**Oxidative Stress Relief in Erythrocytes**

* glycogen -\> glucose 6-phosphate -\> glucose and the glucose is transported through the bloodstream to cells that need it

Glycogen storage in the liver

* glycogen -\> glucose-6-phosphate and it stays INSIDE the muscle to provide energy) * Muscles lack glucose-6-phosphatase so unable to convert G6P into glucose and instead directly starts glycolysis with G6P)

Glycogen storage in the skeletal muscles

Which hormone simulates glycogensis and inhibits glycogenolysis

Insulin

* **the process of storing excess glucose for use by the body at a later time**. * Stimulated by insulin * inhibited by epinephrine and glucagon

glycogenesis

* process that occurs when the body, which prefers glucose as an energy source, needs energy. The glycogen previously stored by the liver is broken down to glucose and dispersed throughout the body * inhibited by insulin * stimulated by epinephrine and glucagon

**Glycogenolysis**

* Transfer of an amino group from one Carbon skeleton to another * ransfer of an alpha amino group from an amino acid to an alpha-ketoglutarate * Results in an Glutamate and an alpha-Keto acid * Note that glutamate now holds the Ammonia from the Amino Acid’s amino group. * Catalyzed by *Aminotransferases* * All AAs participate except lysine and threonine (go straight to deamination). (**L**et **The**m Deanimate)

Transamination

* Amino Acid Catabolism where liberation of amino group as free ammonia * Glutamate and NAD+ to alpha-ketoglutarate and NADH catalyzed by *glutamate dehydrogenase* * Ammonia transported to the liver.

Deamination

* Tissues: liver, lactating mammary glands, adipose tissue * Location: **cytosol** * Generalized process: incorporates carbons from acetyl-CoA into the growing fatty acid chain (two carbon units at a time) * Acetyl-CoA from mitochondria needs to go to cytosol for fatty acid synthesis so acetyl-CoA combines with oxaloacetate to make citrate and utilizes the citrate shuttle to cross the membrane and reconvert to oxaloacetate and acetyl-CoA * _Rate-limiting step: Acetyl-CoA –(_*_acetyl-CoA carboxylase_*_)→ malonyl-CoA_ * End result: palmitic acid (16:0)

**Fatty Acids** De Novo Synthesis

* Location: **mitochondrial matrix** * Generalized process: Fatty acyl coA (Chain shorter than 12 C’s can pass through w/t shuttle) (remember, the active form of a FA is w/ a coA) cannot pass through inner mito membrane; must remove coA, place carnitine (carnitine shuttle), then FA is transported from the cytosol to mitochondria. Put coA back on FA. Then remove 2-carbon fragments at a time. * End result: acetyl-coA (2 carbons) or propionyl-CoA (3 carbons) * Propionyl-CoA can be metabolized to succinyl-CoA in order to enter the kreb cycle

Fatty Acids Beta Oxidation

* Primary essential fatty acids: linoleic acid (ω-6), α-linoleic acid (ω-3) * Arachidonic acid is derived from linoleic acid (ω-6)

Essential fatty acids

high levels of ketone body formation (specifically acetone) rise in the blood and urine → symptom of this is fruity odor of the breath

Uncontrolled type I diabetes (diabetic ketoacidosis)

* acetoacetate, acetone, 3-hydroxybutyrate

ketone bodies

* Synthesis * 2 Acetyl-CoA -\> HMG-CoA * _HMG-CoA -\> Mevalonate through HMG-CoA reductase (Rate limiting step)_ (Statins also inhibit this enzyme to lower cholesterol levels) * Mevalonate -\> Squalene -\> Cholesterol

Cholesterol Metabolism Synthesis

* (Degrades cholesterol into bile acids -\> bile salt) * Cholesterol -\> 7-α-hydroxycholesterol through Cholesterol 7-a-hydroxylase (_Rate limiting enzyme in bile acid synthesis)_

Cholesterol metabolism degradation

* lipoprotein particle that is produced in liver. * contains lipids that are produced by the body (_NOT from die_t) and delivers to the cells. * TAGs are preferentially drawn off to fat cells and muscles and then become LDL.

VLDL

* Lipoprotein Particles that is bad cholesterol. * Delivers cholesterol to tissues. (Do not contain TAGs)

LDL

* Lipoprotein that is called good cholesterol. * Picks up cholesterol from peripheral tissues to liver. (Do not contain TAGs)

HDL: good cholesterol. Picks up cholesterol from peripheral tissues to liver. (Do not contain TAGs)

* Chylomicrons: comparatively large packets of phospholipids, unesterified cholesterol, and apolipoprotein and main source of TAG’s delivered to tissues. (Chylomicrons increase the solubility of the lipids when in the lipoprotein complex.) * TAGs are more on the outside of the chylomicrons nearer to the membrane, hence they are absorbed by the muscle and fat cells. * Remnants of the chylomicrons are hydrolyzed by the liver into their component parts. * Apolipoproteins, phospholipids and unesterified cholesterol are found in the chylomicron membranes.

Chylomicrons

* Prostaglandins are derived from Arachidonic acid derived from Linoleic acid in which COX-1 and COX-2 enzyxgmes give rise to Prostaglandins and Thromboxanes * Inhibited by XXX

(COX-1 and COX-2 inhibited by NSAID like aspirin to give pain relief)

* You can generate Phospholipid -\> Arachidonic acid through phospholipase A2 * (Inhibited by corticosteroids like cortisol)

* Arachidonic acid can also give rise to leukotrienes through 5-lipoxygenase. * This is inhibited by NSAIDS - True/False

False

* Purine Metabolism * Purine synthesis begins with Ribose-5-Phosphate (from PPP) and gets converted to PRPP using **_PRPP Synthetase_** * PRPP is then converted to IMP with the help of some AA * IMP is then converted to AMP and GMP (IMP is the first purine made here) * AMP and GMP are then converted to dAMP and dGMP by **_Ribonucleotide Reductase_** * This step is inhibited by Hydroxyurea (anti-cancer drug)

* Salvage Pathways of Purine synthesis is also available * Hypoxanthine → IMP * Done by **_Hypoxanthine-Guanine phosphoribosyltransferase_** * Guanine → GMP * Done by **_Hypoxanthine-Guanine phosphoribosyltransferase_** * Adenine → AMP * Done by **_Adenine phosphoribosyltransferase_**

* Purine Degradation * AMP, GMP, and IMP all get converted to Uric Acid * However, when there is an abundance of Uric Acid it will lead to Gout * This is treated by using allopurinol which will inhibit the enzyme responsible for creating Uric Acid which is **_Xanthine Oxidase_**

* Pyrimidine Synthesis begins with the AA Glutamine. * Glutamine is converted to UMP which can in turn get converted to CMP and TMP * dUMP is converted to dTMP by **_thymidylate synthase_** * There is an addition of a methyl group in this reaction which is done by the help of another enzyme, **_dihydrofolate reductase,_** which uses NADPH and Serine to give what is needed to create the methyl group. * This is what I feel is important. Serine/NADPH are the methyl donors

Pyrimidine regulation Inhibits thymidylate synthase

5-fluorouracil

pyrimidine regulation Inhibits dihydrofolate reductase

Methotrexate

Pyrimidine breakdown leads to

Beta-Amino Acids, CO2, and NH3

The enzyme responsible for initiating the retrieval or mobilization of stored fatty acids from their TAG form. This enzyme removes fatty acid from carbon 1 and or carbon 3 of the TAG.

***Hormone Sensitive Lipase***

* Hormone that is found in the capillary beds of skeletal muscle and adipose tissue that breaks down TAGs*.* Fatty acids are taken up by muscle cells and fat cells (typically for storage), whereas glycerol is used almost exclusively by the liver to make glycerol-3-phosphate which can enter glycolysis or gluconeogenesis. * The fatty acids stored in adipose tissue, in the form of TAG, serve as the body’s major fuel storage reserve.

***Lipoprotein Lipase***

**TAG Synthesis/Degradation** * In the synthesis of TAG, Glycerol Phosphate is the initial acceptor of fatty acids, and is synthesized in the liver or adipose tissue. * Only activated fatty acids can participate in TAG synthesis, and activation of fatty acids is catalyzed by ***Fatty acyl CoA synthetase*** which activates the fatty acids by adding a CoA group to them. * TAGs are the primary target of degradation by lipase in the stomach, and pancreatic lipase in the small intestine. * After absorption into enterocytes, TAG is resynthesized and packaged into chylomicrons. These chylomicrons are released by exocytosis into lacteals and follow the lymphatic system then enter the blood.

**List of Molecules that are Derived from Amino Acids** * Heme: derived from Glycine * Histamine: derived from Histidine * Serotonin: Tryptophan * Creatine: Glycine and Arginine * Melanin: Tyrosine

* Glycine + Succinyl CoA → Heme (the prosthetic group of hemoglobin, myoglobin, the cytochromes, catalase, nitric oxide synthase, and peroxidase) * Enzymes and their inhibitors/activators (in order of the pathway): * *_ALAS 1:_* inhibited by heme. * *_ALAS 2:_* inhibited by **lack** of iron (Iron is an activator). * *_S-Aminolevulinic Acid Dehydratase:_* inhibited by lead. * *_Ferrochelatase:_* inhibited by lead.

**Heme Synthesis/Degradation**

* Heme Degradation (occurs after about 120 days in circulation; degraded in liver and spleen) * Heme → biliverdin by **Heme Oxygenase** * This step releases Carbon Monoxide which is main step that creates CO in our body * Biliverdin → bilirubin * Biliverdin reductase

Heme degradation

* Over accumulation of phenylalanine due to insufficient phenylalanine hydroxylase (Converts Phenylalanine → Tyrosine) enzymes. * Can be regulated with a strict low phenylalanine diet.

Amino Acid disoeswe - PKU

* Albinism- Lack of Tyrosinase = No melanin * Albinos can develop skin cancer early.

Amino Acid disorder - Albinism

* Part of Thiamine Pyrophosphate (TPP) (Coenzyme in PDH complex in conversion of pyruvate to acetyl-CoA) * Deficiencies: Beriberi, Wernicke-Korsakoff Syndrome

B1 (thiamin)

(Riboflavin)- Deficiencies: Cheilosis, Glossitis

(Niacin)- Coenzyme forms: NAD, NADP. Deficiencies: Pellagra

* (Pantothenic Acid) * critical to the manufacture of red blood cells, as well as sex and stress-related hormones produced in the adrenal glands, small glands that sit atop the kidneys.

Vitaminn B5

* (Pyridoxine/Pyridoxal/ Pyridoxamine)- Important for catecholamine synthesis (amino acid metabolism). * (PLP). Pyridoxine only water soluble vitamin with significant toxicity. ^^^ Also can be stored in muscle (An exception since most water soluble vitamins cannot be stored) Deficiencies: Scaly dermatitis, anemia

Biotin- Used in carboxylation rxns (acetyl-CoA carboxylase in fatty acid synthesis)

* Folic Acid - Tetrahydrofolate (THF). Important for pregnant women and DNA synthesis * Deficiencies: Anemia, Spina bifida, anencephaly

* Cobalamin- New cell synthesis. Binds to Intrinsic Factor. Deficiencies: * Pernicious anemia

B12

* ascorbic acid) : Collagen synthesis, good for hydroxylation. * Deficiency: Scurvy

Vitamin C

fat soluble vitamines

ADEK

* vitamin Important for vision. Deficiencies: Night blindness, Xerophthalmia, * Keratomalacia

Vitamin A

* calciferol: Mineralization of Bone. Get it from the sun. Deficiencies: Rickets * children), Osteomalacia, Osteoporosis

Vitamin D

type of vitamin (tocopherols): Antioxidant. Deficiencies: RBC breakage, nerve damage

Vitamin E

* vitamin (phylloquinone, menaquinone): Blood clotting protein synthesis, bone protein (Also is the only fat soluble vitamin with a coenzyme function) Synthesis. Deficiency: Hemorrhaging

Vitamin K

* Rate-limiting enzyme: c_arbamoyl phosphate synthe_**_t_**_ase I (N-Acetylglutamate is an essential activator)_ * Occurs in mitochondrial matrix AND cytosol * In mitochondrial matrix: carbamoyl phosphate synthetase I → L-citrulline → goes into cytosol * In cytosol: Aspartate comes in, arginase releases urea, L-ornithine is transported back into the mitochondria + is converted back to L-citrulline * Where does Urea get its N and C atoms? * N: from NH3 (ammonia), aspartate * C: from CO2

Urea Cycle

**Role of Insulin and Glucagon** * **TAG Synthesis will occur in response to** **Insulin. Ingestion of excess carbs and calories will synthesize TAG for storage in adipose tissue. (Like how glycogen** ***_synthesis_*** **occurs in response to insulin)** * TAG Degradation will occur in response to **Glucagon and Epinephrine** as a result of a calorie-deficient diet. * Remember: * Insulin will ↓↓ blood sugar * Glucagon and Epinephrine ↑↑ blood sugar.

**BMI** * Formula: weight **(kg)/** height **(m)^2** * 1 kg = 2.2 lbs * 1m = 39.37 in * Categories: Underweight: (\<18.5) /Healthy weight: (18.5-24.9) /Overweight (25-29.9) /Obesity (30-39.9) /Extreme obesity (\>= 40) * General disease risk levels : * Young men: 22%; Men 40+: 25% * Young women: 32%; Women 40+: 35% * Visceral Fat: Upper body fat/Central obesity (common in men) * Subcutaneous fat: Lower body fat (common in women)

**Acceptable macronutrient distribution ranges:** * For adults: * 45-65% of total calories from carbohydrates (4 cal) * 20-35% from fat (9 cal) * 10-35% from protein (4 cal)

**Maintaining Body Weight:** * Sedentary adults: 30 kcal/kg/day * Moderately active: 35 kcal/kg/day * Very active: 40 kcal/kg/day

**Lipoprotein Lipase (effect from obesity)** Removes TAGs from blood for storage in adipose tissue and muscle cells Obese people have more LPL activity in adipose tissue than lean people After Weight loss, LPL activity increases Body tries to regain lost weight

**Leptin/Adiponectin** * Acts as a hormone * Leptin in **adipose tissue:** Promotes negative energy balance by suppressing appetite * Leptin in **stomach:** Released in response to the presence of food. Very few obese people have a leptin deficiency but instead **leptin resistance** * Adiponectin: Lean people have higher amounts. Increases insulin sensitivity

_Phospholipids_ * Phospholipids have Phosphate with a Glycerol (glycerophospholipids) or Sphingosine (sphingophospholipids) backbone * Most abundant are **phosphatidylethanolamine** and **phosphatidylcholine** * PLA1 cleaves at C1, PLA2 cleaves at C2, PLC cleaves before the phosphate, PLD cleaves after the phosphate * Sphingomyelin is an important constituent of myelin fibers. * ***Sphingomyelinase removes phosphorylcholine from Sphingomyelin, leaving a ceramide.*** ***Ceramidase*** removes a fatty acid from Ceramide, leaving a Sphingosine.

**_Glycolipid_**s have a sphingosine backbone and NO phosphate. They are derivatives of ceramides and are an essential component of nerve tissue. * Cerebrosides: simplest neutral (uncharged) * Gangliosides: negatively charged due to N-acetylneuraminic acid (NANA) * Sulfatides: negatively charged due to sulfate groups ![]()