If there is a carboxylase that uses ATP and CO2 it NEEDS Biotin
Gluconeogenesis
What are the 3 steps for gluconeogeneis
Rate limiting step for glycolysis
PFK-1
Rate Limiting for Gluconeogenesis
F1,6 bisphosphatase-1
 Activated by ATP has a lot of energy, so you don’t need the TCA cycle
Rxn F-6-P  F1,6,P
F2,6bP ↑ ↑ ↑ when eating ↑ ↑ glycolysis
Glucose 6 Phosphatase is found in the (Organs) Liver and Kids
Cellular Location? (weird)
RXN: G6P GLUCOSE
Other Organs G6P Glycogen
EVEN chain FA CAN become glucose.
TAG breakdown Glycerol   Dihydroxyacetone
PhosphateGlycolysis/Gluconeo
Cortisol/steroids: ↑ ↑ [Enzymes for Gluconeogenesis]   ↑↑[Glucose]
Diabetes
Thyroid Hormone: ↑ ↑ Gluconeogenesis
Fatty Acids
Triglyceride ==TAG
Lipid Metabolism:
Intestines
Lipids Free FA
FA TAG (in enterocyees)
TAG goes in Chylomicrons in blood
TAG Free FA (In Adipocyees and muscles ) by Lipoprotein lipase
SAT vs UNSAT fats
 SAT: more saturated SOLID
 UNSAT
o Cis fat
o Trans fat (Unnatural)
o Omega 3 Fa (3 carbons from the tail of the fat
FA SYNThesis
1. Liver
2. Adipose
After a MEAL  ↑ ↑ [ATP] & [Acetyl-CoA]
ATP--| Isocitrate Dehydrogenase (TCA) resulting in ↑ ↑ CITRATE (Citrate Shuttle)
Acetyl-CoA CANNOT exit the mitochondria but CITRATE CAN
Step2: (In Cytosol)
Citrate  Acetyl-CoA (ATP-Citrate Lyase)
STEP 3 (RATE LIMITING)
Acetyl CoA Malonyl CoA (Acetyl CoA Carboxylase) SUPER IMPORTANT
 Rxn Uses CO2 and BIOTIN
Product of FA Synthesis (Malonyl CoA) INHIBITS [B-OX]
BIOTIN
Pry Carboxylase
Acetyl-CoA Carboxylase
STEP 4
FA Synthase makes MALMITATE (16C) FA from Acetyl and Malonyl CoA
USES NADPH
Palmitate Other FA
ACTIVATORS
1. Insulin
2. Citrate
INHIBITORS
1. Glucagon
2. EPI
FA STORAGE
1. Palmitate--_ TAG
2. Adipose Tissue TAG
Breakdown
(HORMONE SENSITIVE LIPASE): Removes FA from TAG (In Adipocytes)
Activated by Glucagon and EPI
1. B-OX (Acetyl CoA)
2.
FA transported bound to ALBUMIN in Blood B-OX
What 2 organs cannot use FA for energy?
RBC (no mitocondrria) & BRAIN
B-OX
1. Remove 2 C from a molecule
2. What does it Make???
a. Acetyl Coa, NADH, FADH2
3. STEPS
a. 1 FA FA-CoA (LONG Chain FA CoA Syn)
i. Use ATP
b. 2. Transport FA-CoA Inner Mito (Carnitine Shuttle)
i. Carnitine
1. Liver & Kidneys MAKE it from Lysine and Methionine
2. MUSCLES and HEART need it from DIET
ii. FA- CoA enters Inner Mito Membrane Space but CANT enrer
Matrix
iii. FA-CoA  Acyl Carnitine (Carnitine Palmitoyl Transferase-1)
CAT-1
1. CPT-1 is turned OFF by Malonyl-CoA (↑↑ when we
are MAKING FATS)
2. Acyl Carnitine  Acetyl-CoA(CPT-2)
iv. Carnitine Deficiency CAN’T BREAKDOWN FA
1. Causes
a. Malnutriation
b. Liver Disease
c. Used up (Trauma, burns, pregnancy)
d. Dialysis (CKD) Taken out of blood
2. RESULT
a. Can’t transport LCFA to mito ↑↑↑[Long
FA](in cytosol)
3. Diagnose:
a. ↓↓[Carnitine] & Acyl-carnitine
4. S/S
a. Muscle Weakness (During Exersize)
b. Heart Issues
c. Hypoketotic Hypoglycemia when fasting
i. No Glucose
ii. ↓FA breakdown ↓↓Ketone Synthesis
5. Congenital Disease
a. Can’t bring Carnitine INTO cells
b. LOW Carnitine
c. 3. B-OX
i. remove 2 carbons atarting at start of carboxyl group (a carbon,
b carbon)
1. Acyl-CoA Dehydrogenase (4 TYPES depending on
length of chain)
a. MAKES FADH2
b. Medium Chain
ii. MCAT deficiency (LOW Acetyl-CoA levels)
1. Mewdium chain Acyl-CoA Dehydrogenase
2. AR disorder
3. Hypoglycemia w/o ketones
4. CANT break down 6-10 FA ↑↑↑[Acyl Carnitine]
(diagnostic)
5. Gluconeogenesis Shutdown
a. ↓[Acetyl CoA]↓↓Pyr Carboxylase activity
b. Worse in Fasting/
iii. ODD CHAIN FA CAN TURN INTO glucose
1. B-OX until 3 carbons
2. Prop-CoA Succ-CoATCA
iv. PROPINYL-CoA (IMPORTANT MOLECULE)
1. Amino Acids  Prop-CoA
2. CholesterolProp CoA
3. ODD CHAIN FA Prop CoA
v. Prop-CoAMethylmalonyl-CoA Succ-CoA
1. 1srt step needs: Biotin
2. 2nd Step Needs: B12
a. B12 Deficiency↑↑[Methylmalonic Acidemia]
vi. Methylmalonic Acidemia
1. Causes
a. B12 deficiency or
b. Deficiency of Methylmalonyl-CoA mutase
2. S/S
a. Anion Gap Metabolic Acidosis
b. CNS dysfunction
c. Fatal as kid
In Zellweger syndrome and X-linked adrenoleukodystrophy (XALD), the lack or
dysfunction of peroxisomes, respectively, leads to
accumulation in the blood of very long-chain FA, causing loss of vision, behavioral
disturbances, and death
Propinyl-CoA Carboxylase (
d. Needs Biotin
4. B12 deficiency leads to incorporation of Methylmalonyl-CoA instead of
malonyl-CoA in lipid synthesis. Misincorporation during formation of
myelin sheaths leads to neuropathy!
5. B12 deficiency is seen in: malabsorption (alcohol excess, infections) lack
of intrinsic factor (pernicious anemia, gastric bypass) dysfunction of
terminal ileum (Crohn’s disease, surgical resection) or veganism
6.
i.
7.
STEP