Cholesterol Biosynthesis

Citrate transport system moves acetyl CoA from mitochondria into cytoplasm. Thiolase, HMG CoA synthase, and HMG CoA reductase (rate-limiting) convert it into mevalonate. Mevalonate is then converted into IPP and then cholesterol.

Cholesterol can be esterified and stored in the cell via ACAT, or it can be secreted as a lipoprotein and then converted via LCAT.

Transcriptional Control
If there is a high level of cholesterol, it binds to SCAP and inactivates it. If there is low cholesterol, then SCAP is active. SCAP-SREBP can be transported into the Golgi, where the proteases cleave off the DNA binding domain. That DNA binding domain goes into the nucleus and interacts with SRE. SREBP can then activate the genes for HMG CoA reductase synthesis.

Post-transcriptional control includes proteolysis of the reductase or degradation of the HMG CoA reductase mRNA.

Phosphorylation
Glucagon --> phosphorylation of HMG CoA reductase via kinase like AMPK --> decrease cholesterol synthesis
Insulin --> dephosphorylation of HMG CoA reductase via phosphatase --> increase cholesterol synthesis

Respiratory Control Mechanisms

2,3-BPG

2,3 BPG is produced by erythrocytes when there are low levels of oxygen, like at high altitudes. 2,3 BPG shifts the oxygen dissociation curve to the right so that hemoglobin has reduced affinity for oxygen. This results in an increased in O2 delivery to the tissues.

1,3 BPG, the precursor to 2,3 BPG, is formed during one of the steps in glycolysis. In hypoxic environments, it does not become pyruvate but instead is converted into 2,3 BPG by BPG mutase. As a result, the cell is sacrificing the formation of ATP for increased O2 delivery.

Chiari I and II Malformations

Chiari I malformation is when the lower part of the cerebellum extends into the foramen magnum. Type I may not cause any symptoms. In fact, it may not detected until much later in life.

Chiari II malformation (Arnold-Chiari malformation) is the herniation of the cerebellar vermis and brain stem through the foramen magnum. The herniation can then cause hydrocephalus. Type II is associated with myelomeningocele. During antenatal care, an ultrasound may show a lemon or banana sign. Infants may display symptoms such as stridor (sounds like a seal), dysphagia, hypotonia, and ataxia.

https://rarediseases.info.nih.gov/diseases/9232/chiari-malformation-type-2
https://radiopaedia.org/articles/chiari-ii-malformation

Rib Ligaments

Shock

Special thanks to Siu Lam, Janeah, and Deb!

Wigger's Diagram

Special thanks to my friends, Siu Lam and Janeah, for going through this a third time with me...