Disease starts at the level of the cell Long before we see disease in tissues or organs, there are changes in the biochemistry of the cell.
Chondrocytes • Before arthritis manifests in the joints, the cells dedicated to making the cartilage that cushions and lubricates the joint, start to fail. They are unable to replace the cartilage at a fast enough rate to compensate for the daily loss due to use of the joint.
Heart People prone to muscular cramps are more likely to get cardiac muscle cramp at a later stage in life.
Vitamin C is an essential component for neutrophil apoptosis. The vitamin C content in a macrophage cell can reach 40 times higher than the vitamin C content in blood.
Red Blood Cells Vit C needed for • Production • Maintenance • Function
RBC become less ‘sticky’ • WBC also
Cholesterol Vitamin C regulates cholesterol synthesis in the liver. This means that by keeping your vitamin C levels up, your body can more efficiently carry LDL (bad cholesterol) from the arteries to the liver for processing. This can greatly reduce your blood cholesterol levels without changing the chemistry of your body.
The enzyme responsible for the first step in converting cholesterol to bile acids, cholesterol-7-alpha hydroxylase, depends on vitamin C. • Vit C is part of the rate- limiting step of cholesterol lowering.
Ascorbate Roles in Metabolism • PROLINE --> HYDROXYPROLINE • TRYPTOPHAN --> SERATONIN • TYROSINE --> NOREPINEPHRINE • OSTEOBLASTS --> WOUND REPAIR • VASO-HUMORAL --> BLOOD FLOW • TOXICANTS -->MIXED Fn OXIDASES • STEROIDS -->STEROLS • Fe3+ -->Fe2+ • Cu2+ -->Cu1+ • Se4+ --> Se2+ • CHOLESTEROL -> BILE ACIDS
Krebs Discovered the citric acid cycle in 1937 . It is the central metabolic pathway for all aerobic processes. The cycle provides the complete oxidation of C2 units (acetyl-CoA) derived from fats, carbohydrates and lipids into carbon dioxide and water capturing the released energy as reductive power in the form of NADH and FADH2. The cycle also provides metabolic intermediates for biosynthetic purposes.
The mitochondrial myopathies or encephalomyopathies with known biochemical defects can be divided into 5 groups: • (1) defects of mitochondrial transport, such as CPT deficiency or carnitine deficiencies; • (2) defects of substrate utilization, such as PDHC deficiency or defects of -oxidation; • (3) defects of the Krebs cycle, such as fumarase deficiency; • (4) defects of oxidation-phosphorylation coupling, such as Luft disease, • (5) defects of the respiratory chain. These disorders are reviewed, with particular emphasis on the defects of the respiratory chain. Defects of complex I, III and IV show remarkable clinical and biochemical heterogeneity. All 3 complexes contain some subunits encoded by mtDNA and others encoded by nuclear DNA. At least some of the cytoplasmically made subunits appear to be tissue specific and may be developmentally regulated, thus explaining the genetic heterogeneity of these disorders. S. DiMauro et al (1987)
The most important emptying processes are the removal of malate and related compounds for the synthesis of carbohydrates, and the export of citrate from the mitochondria for the biosynthesis of fat.
Succinatedehydrogenase and fumaratehydratase: linking mitochondrial dysfunction and cancer A King, MA Selak and E Gottlieb, Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK • The phenomenon of enhanced glycolysis in tumours has • been acknowledged for decades, but biochemical evidence • to explain it is only just beginning to emerge. A signiﬁcant • hint as to the triggers and advantages of enhanced • glycolysis in tumours was supplied by the recent discovery • that succinatedehydrogenase (SDH) and fumarate • hydratase (FH) are tumour suppressors and which • associated, for the ﬁrst time, mitochondrial enzymes and • their dysfunction with tumorigenesis
2H or Charcoal Block ? Decreased semen ascorbate level plays a significant role in the reduced sperm characteristics in males.
American Association of Cancer Research Low Ascorbate Levels Are Associated with Increased Hypoxia-Inducible Factor-1 Activity and an Aggressive Tumor Phenotype in Endometrial Cancer Caroline Kuiper, Ilona G.M. Molenaar, Gabi U. Dachs, Margaret J. Currie, Peter H. Sykes, and Margreet C.M. Vissers