From f605433ee9776e226491e5221abec61d98979fe3 Mon Sep 17 00:00:00 2001
From: Johan Dahlin <jdahlin@gmail.com>
Date: Tue, 9 Dec 2025 11:34:16 +0100
Subject: [PATCH] vault backup: 2025-12-09 11:34:15

---
 .../Pasted image 20251209111439.png           | Bin 0 -> 14692 bytes
 .../🧬 Nukleotidnedbrytning/Slides.pdf.pdf    |   3 +
 .../🧬 Nukleotidnedbrytning/👨🏻‍🏫 Slides.md  | 312 ++++++++++++++++++
 .../🧬 Nukleotidnedbrytning/🗒 Anteckningar.md |  44 +++
 4 files changed, 359 insertions(+)
 create mode 100644 content/attachments/Pasted image 20251209111439.png
 create mode 100644 content/🧪 Biokemi/🏋️‍♀️ Metabolism/🧬 Nukleotidnedbrytning/Slides.pdf.pdf

diff --git a/content/attachments/Pasted image 20251209111439.png b/content/attachments/Pasted image 20251209111439.png
new file mode 100644
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diff --git a/content/🧪 Biokemi/🏋️‍♀️ Metabolism/🧬 Nukleotidnedbrytning/👨🏻‍🏫 Slides.md b/content/🧪 Biokemi/🏋️‍♀️ Metabolism/🧬 Nukleotidnedbrytning/👨🏻‍🏫 Slides.md
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@@ -6,3 +6,315 @@ tags:
 föreläsare: Martin Lidell
 date: 2025-12-09
 ---
+Nukleotidnedbrytning  
+LPG001  
+Martin Lidell  
+
+---
+
+## Lecture outline
+
+- Nucleotides – short repetition of structural parts  
+- Functions of nucleotides  
+- Degradation of nucleic acids from food sources  
+- Degradation of purine nucleotides  
+- Degradation of pyrimidine nucleotides  
+- Two diseases related to purine nucleotides  
+  - Gout – a very common disease  
+  - Adenosine deaminase deficiency – a very rare disease  
+
+---
+
+## What is a nucleotide?
+
+- Nucleotide = Phosphate(s) + Pentose + Nitrogenous base  
+- Nucleoside = Pentose + Nitrogenous base  
+- Adenosine monophosphate  
+- OH (in ribose) or H (in deoxyribose)  
+
+---
+
+## The nitrogenous bases – purines and pyrimidines
+
+- Five bases  
+- PURINES: Purine, Adenine, Guanine  
+- PYRIMIDINES: Pyrimidine, Cytosine, Uracil (in RNA), Thymine (in DNA)  
+- Two rings; two purines  
+- Three pyrimidines; pyramide from above; CUT  
+
+---
+
+## Functions of nucleotides – some examples
+
+- Building blocks for DNA and RNA (store and translate genetic information)  
+- Building blocks for important biomolecules (e.g. Coenzyme A)  
+- Signaling molecules (both extra- and intracellular) (e.g. cAMP, adenosine signaling – a nucleoside)  
+- “Activators” of biomolecules used for biosynthesis  
+  - UDP-Glucose (activated form of glucose; glucose donor in glycogen synthesis)  
+
+---
+
+## Overview of nucleotide metabolism
+
+- Nucleotides  
+  - De novo synthesis  
+  - Salvage synthesis (synthesis from reused nitrogenous bases and sugars)  
+  - DNA and RNA synthesis  
+  - Conversion to other important biomolecules  
+  - Degradation  
+
+- From degradation:  
+  - Nitrogenous bases →  
+    - Reuse for nucleotide synthesis (salvage)  
+    - Further degradation →  
+      - Purines → Urate + Urea  
+      - Pyrimidines → Urea + Energy or energy-rich molecules  
+  - Sugar moiety →  
+    - Reuse for nucleotide synthesis (salvage)  
+    - Energy source (ATP or energy-rich molecules)  
+
+---
+
+## Expensive with de novo synthesis of nucleotides – the salvage pathway is cheaper
+
+- De novo pathway vs salvage pathway  
+- PRPP; 5-Phosphoribosyl 1-pyrophosphate  
+
+---
+
+## Degradation of nucleic acids from food sources
+
+- Degradation of dietary nucleic acids occur in the small intestine  
+- Nucleases, secreted by the pancreas, hydrolyze RNA and DNA to oligonucleotides  
+- Oligonucleotides are further hydrolyzed by pancreatic phosphodiesterases, producing mononucleotides  
+- In the intestinal mucosal cells (intestinal epithelial cells), nucleotidases remove the phosphate groups, releasing nucleosides that are further degraded to free bases and sugars by nucleosidases  
+- The liberated bases can potentially be used in salvage pathways for nucleotide synthesis (however, at least the purines appear to be degraded to a large extent already in the intestinal cells)  
+
+---
+
+## Nucleotide degradation pathways
+
+- Nucleotides → Degradation →  
+  - Nitrogenous bases →  
+    - Reuse for nucleotide synthesis (salvage)  
+    - Further degradation →  
+      - Purines → Urate + Urea  
+      - Pyrimidines → Urea + Energy or energy-rich molecules  
+  - Sugar moiety →  
+    - Reuse for nucleotide synthesis (salvage)  
+    - Energy source (ATP or energy-rich molecules)  
+
+---
+
+## Degradation of purine nucleotides – formation of uric acid
+
+- GMP → (via nucleotidases) → Guanosine  
+- Nucleotidases convert the nucleotides into nucleosides  
+- Guanosine → Guanine (and further degradation)  
+- Pathway towards hypoxanthine, xanthine and uric acid  
+
+---
+
+## Adenosine deaminase – an important enzyme in the degradation of adenosine
+
+- Adenosine is deaminated to inosine by adenosine deaminase  
+- Toxic ammonia converted into urea in the liver  
+- Parallel pathway: GMP → Guanosine → Guanine, etc.  
+
+---
+
+## The sugar parts are removed by nucleoside phosphorylase
+
+- GMP → Guanosine  
+- Sugar phosphates options:  
+  1. Reuse for nucleotide synthesis (convert to PRPP)  
+  2. Use for energy production or generation of energy-containing molecules  
+- The sugar parts are removed by nucleoside phosphorylase  
+
+---
+
+## GMP and AMP degradation converge at the level of xanthine that is further metabolized to uric acid
+
+- Toxic ammonia converted into urea in the liver  
+- Uric acid (urate) excreted in the urine  
+
+---
+
+## Degradation of pyrimidine nucleotides
+
+- Pathways for CMP, UMP and dTMP  
+- Intermediates within brackets refer to metabolites from dTMP degradation  
+
+---
+
+## CMP and UMP degradation converge at the level of uridine
+
+- Nucleotidases convert the nucleotides into nucleosides  
+- CMP, UMP → Uridine  
+- Toxic ammonia converted into urea in the liver  
+
+---
+
+## The sugar part is removed by a phosphorylase to generate the free pyrimidine bases
+
+- Options for sugar phosphates:  
+  1. Reuse for nucleotide synthesis (convert to PRPP)  
+  2. Use for energy production or generation of energy-containing molecules  
+
+- Options for free bases:  
+  1. Reuse for nucleotide synthesis  
+  2. Use for energy production (ATP) or generation of energy-containing molecules  
+
+---
+
+## Complete degradation of nitrogenous bases for ATP production or generation of energy-containing molecules
+
+- From CMP and UMP:  
+  - Acetyl CoA (Propionyl CoA) → ATP, fatty acids or ketone bodies  
+- From dTMP:  
+  - Succinyl CoA (CAC intermediate) → ATP or glucose production  
+- Enzymes/intermediates:  
+  - Methylmalonate semialdehyde dehydrogenase  
+  - Propionyl CoA carboxylase  
+  - Methylmalonyl CoA  
+  - Methylmalonyl CoA mutase  
+- Toxic ammonia converted into urea in the liver  
+
+---
+
+## What happens with the sugar moiety produced during nucleotide degradation?
+
+- Ribose-1-phosphate ↔ (Phosphopentomutase) ↔ Ribose-5-phosphate  
+- Deoxyribose-1-phosphate ↔ Deoxyribose-5-phosphate  
+- Ribose-5-phosphate can enter the pentose phosphate pathway (transketolase and transaldolase)  
+- Deoxyribose-5-phosphate → (Deoxyribose phosphate aldolase) → Glyceraldehyde-3-phosphate + Acetaldehyde  
+- Fructose-6-phosphate + Glyceraldehyde-3-phosphate → glycolysis/gluconeogenesis connection  
+- Acetyl CoA from acetaldehyde → ATP, fatty acids or ketone bodies  
+- Can be reused for nucleotide synthesis (converted to PRPP)  
+
+Endproducts used for energy production or generation of energy-containing molecules:
+
+- Fructose-6-phosphate and glyceraldehyde-3-phosphate: ATP or glucose production  
+- Acetyl CoA: ATP, fatty acids or ketone bodies  
+
+---
+
+## Full degradation of pyrimidines and purines
+
+**Pyrimidines**
+
+- Generate ammonia (NH₃) that is converted into UREA by the liver and excreted in the urine  
+- Metabolites that can be used for energy production (ATP) or converted into energy-containing molecules such as glucose (liver), fatty acids and ketone bodies  
+
+**Purines**
+
+- Primarily generate URIC ACID (urate) that is excreted in the urine  
+- Some ammonia is also produced; converted into urea by the liver  
+
+---
+
+## Gikt – från ”the disease of kings” till folksjukdom
+
+- Vid för höga uratnivåer i blodet (>6–7 mg/dl) fälls urat ut som saltkristaller (ofta natriumurat)  
+- Kristallerna lägger sig i leder, senor och omgivande vävnad (vanligast är stortåns grundled) och orsakar där inflammation  
+- Vanligaste artritsjukdomen (uppskattad förekomst i Sverige, 1–2 % av befolkningen)  
+- De höga uratnivåerna i blodet beror antingen på ökad syntes eller på minskad utsöndring av urat  
+- Beror oftast på livsstilsfaktorer, läkemedelsbehandling eller annan sjukdom  
+
+Preventiva åtgärder inkluderar bland annat:
+
+- Minskat intag av alkohol. Vid metabolism av etanol bildas laktat som kompetitivt hämmar utsöndring av urat i tubuli  
+- Minskat intag av purinrika livsmedel (främst inälvsmat, sardiner, ansjovis och musslor, men även övrig fet fisk, skaldjur och kött)  
+
+---
+
+## Läkemedelsbehandling av gikt – strategi 1
+
+- Hämma bildningen av urat genom att hämma enzymet xantinoxidas som ansvarar för sista steget i nedbrytningen av puriner  
+- Exempel på läkemedelssubstanser som hämmar produktionen av urinsyra:  
+  - Allopurinol (hypoxantinanalog)  
+  - Febuxostat  
+
+---
+
+## Läkemedelsbehandling av gikt – strategi 2
+
+- Hämma reabsorptionen av urat från urinen i njurtubuli genom att inhibera urattransportörer (dessa återför normalt en stor del av utsöndrat urat till blodet)  
+- Ger sänkta uratnivåer i blodet då mer urat avgår med urinen  
+- Exempel på substans: Probenecid  
+
+---
+
+## Svår kombinerad immunbrist (SCID)
+
+- SCID (Severe Combined Immunodeficiency) – samlingsnamn på ett flertal ovanliga sjukdomar som beror på avsaknad av immunceller som T- och B-lymfocyter, vilket leder till ett defekt immunsystem  
+- Utan behandling leder SCID till svår infektionsbenägenhet och drabbade individer avlider ofta redan under det första levnadsåret  
+- Adenosindeaminasbrist; mycket ovanlig form av SCID i Sverige  
+- Autosomal recessiv nedärvning (mutationer i ADA-genen orsakar dysfunktionellt adenosindeaminas)  
+- En närmast total brist på immuncellerna T- och B-lymfocyter ses vid adenosindeaminasbrist  
+
+---
+
+## Svår kombinerad immunbrist (SCID) – till följd av adenosindeaminasbrist
+
+Möjlig koppling mellan enzymdefekt och avsaknad av immunceller:
+
+- Muterat adenosindeaminas som förlorat sin funktion → ansamling av deoxyadenosin som omvandlas till dATP → syntes av övriga deoxyribonukleotider hämmas (dATP hämmar ribonukleotidreduktas) → syntes, replikation och reparation av skadat DNA hämmas → påverkar framförallt snabbt prolifererande celler (celltyper med hög omsättning) som då genomgår apoptos (”programmerat självmord”)  
+- T- och B-lymfocyter under utveckling är mycket snabbt prolifererande celler och tros därför påverkas i speciellt hög grad av tillståndet  
+
+Behandling – går ut på att ge tillgång till ”friskt enzym”:
+
+- Hematopoetisk stamcellstransplantation (benmärgstransplantation) från frisk donator  
+- Enzymsubstitutionsbehandling, dvs enzymet ges som läkemedel (PEG-konjugat ADA injiceras subkutant)  
+- Genterapi; ”frisk ADA-gen” introduceras i individens egna hematopoetiska stamceller  
+
+---
+
+## Genterapi vid adenosindeaminasbrist
+
+- Har utförts på ett fåtal individer där det inte varit möjligt att hitta lämplig donator  
+
+Översikt:
+
+- Virus, med en frisk kopia av ADA-genen tillverkas  
+- De virus man använder saknar förmågan att ge upphov till sjukdom men har kvar egenskapen att bygga in nya gener i vår arvsmassa  
+- Virusen infekterar sedan hematopoetiska stamceller isolerade från den sjuka individens benmärg och för på så sätt in den friska genen i dessa celler  
+- Cellerna ges tillbaka till den sjuka individen som därmed har fått ”friska stamceller” som kan bilda friska T-lymfocyter  
+
+---
+
+## Sammanfattning av nukleotidnedbrytning
+
+- Nukleotider har flera viktiga funktioner förutom att bilda nukleinsyrorna DNA och RNA  
+- Fem kvävebaser:  
+  - Två puriner; två ringar; GA  
+  - Tre pyrimidiner; pyramid från ovan; CUT  
+
+- De novo syntes av nukleotider är dyrt vilket gör att baserna och sockerenheterna återvinns i hög grad  
+
+Om fullständig nedbrytning av nukleotider:
+
+- Sockerdelen kan användas direkt som energikälla (ATP) eller omvandlas till energirika produkter  
+- Kvävebaserna:  
+  - Puriner: URINSYRA (URAT) + mindre mängd urea  
+  - Pyrimidiner: UREA + energirika molekyler som kan användas för direkt produktion av ATP eller omvandlas till energirika produkter  
+
+- Defekter i nukleotidmetabolism kan orsaka sjukdom:  
+  - Gikt; mycket vanlig artritsjukdom; uratkristaller i leder pga höga uratnivåer i blodet  
+  - Adenosindeaminasbrist (form av SCID); mycket ovanlig sjukdom; defekt adenosinnedbrytning orsakar närmast total brist på T- och B-lymfocyter; mycket infektionskänsliga  
+
+---
+
+## Läsanvisningar
+
+- Detta föreläsningsmaterial  
+- Biochemistry, 10th ed, Berg et al.  
+  - 2023 W.H. Freeman, Macmillian Learning  
+  - Kapitel 26: sidorna 809–810  
+
+- Instuderingsfrågor – finns upplagt på Canvas  
+
+Har ni några frågor?  
+Hör gärna av er till mig med ett meddelande på Canvas  
+
+**Nukleotidnedbrytning**
\ No newline at end of file
diff --git a/content/🧪 Biokemi/🏋️‍♀️ Metabolism/🧬 Nukleotidnedbrytning/🗒 Anteckningar.md b/content/🧪 Biokemi/🏋️‍♀️ Metabolism/🧬 Nukleotidnedbrytning/🗒 Anteckningar.md
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@@ -6,3 +6,47 @@ tags:
 föreläsare: Martin Lidell
 date: 2025-12-09
 ---
+Puriner:
+- två ringar - två puriner
+	- adenin
+	- guanin
+
+Pyrimidiner:
+- tre pyrimider, pyramid från ovan
+	- cytosin
+	- uracil
+	- tymin
+	-![[Pasted image 20251209111439.png]]
+
+
+Nukleotiders funktioner
+- DNA/RNA byggstenar
+- activatorer i biomolekyer och biosyntes
+- byggstenar för CoA etc
+- signalering
+
+Det är väldigt dyrt för cellerna att bilda kvävebaser från ingenting (de novo)
+Om det går att återanvända redan uppbyggda kväve baser, de utnyttjar man helst återigen. Länkar till en aktiverad form av ribos.
+
+Vi får in mycket nukleiotider ifrån både växter och animaliska källor
+
+I tarmens epitelceller kan man ta upp nukleosider, tas upp av cellerna och spjälkas ner till kvävebaserna.
+
+Nedbrytas:
+- kvävebaser
+	- återanvändning
+	- fortsatt nedbrytning
+	- urea + urate (puriner)
+		- hela kolskelettet kommer handla i urinsyra
+	- urea + energirika molekyeler (pyrimidiner)
+- sockermolekyl
+	- återanvändning
+	- energikälla
+
+Hur skapas uridsyra?
+1. nukliotider konverteras till nukleosider
+2. spjälkar bort aminogrupp (adenosin → inosine)
+3. ribosen tas bort
+4. hypoxantin
+5. med hjälp av vatten tar bort en 
+