Water Soluble Vitamins
a) Classic example of Vitamin C deficiency: older person on tea and toast diet – indicating
that they are malnourished; pt gets bleeding of the gums = scurvy, due to vit C def. Vit C is
responsible for hydroxylation of proline and lysine, and this occurs in the Golgi apparatus
b/c that’s where post-translational modification occurs. Pts have weak Type I collagen b/c
cannot crossbridge it; therefore, BV’s are unstable and gums bleed. Get bleeding of the
gums, inflammation, and may loose teeth.
b) Associated question: what complication is associated with severe hemophilia A?
Hemearthroses, and caused by Vit C deficiency (b/c the BV’s are unstable and they rupture).
c) Physical diagnosis of Vitamin C deficiency: Along with the tea and toast diet, there is also
perifollicular hemorrhage (hemorrhage around the hair follicles). See ring sideroblast
(nucleated RBC, and has too much iron in the mitochondria), ring around the hair follicle and
also see cork screw hairs due to vit C def. The tongue looks like it hurts and patients with vit
C have a smooth tongue – glossitis, with kelosis around ankles, plus a hemorrhagic diathesis
d) Excess vitamin C: very common b/c pts take way too much vit C (6-8gm), main
complication is Renal stones (increased uric acid stones, and other kinds of stones). Vitamin
C and D both have toxicity stones.
e) Vitamin C is used in ancillary Rx for methemoglobinuria; it is a reducing agent and a great
scavenger hunter for free radicals (knocks them off).
f) Cofactor in biochemical pathway: Vit C is a cofactor for converting the catecholamine NE
Vitamin B 1Thiamine):
a) Involved in many biochemical reactions: transketolase rxn’s in the pentose phosphate
shunt; and pyruvate dehydrogenase; alpha keto glutarate dehydrogenase; and alpha keto
acid dehydrogenase. All the dehydrogenase rxns require thiamine as a cofactor. Pyruvate
dehydrogenase is the main rxn that converts pyruvate into acetyl CoA. Pyruvate can also be
converted to OAA with a carboxylase enzyme. When you combine acetyl CoA with OAA, you
make citrate, and you are in the TCA cycle.
b) So, if thiamine def, b/c it is involved in the pyruvate dehydrogenase rxn (which converts
pyruvate to acetyl CoA), you will not have a lot of acetyl CoA around, therefore, won’t have
much citrate around, therefore, you won’t have the TCA cycle working efficiently, and LESS
ATP. Therefore, the problem with thiamine def is ATP depletion. When you go from
pyruvate to acetyl CoA, you generate 2 NADH’s and since this is in the mito, you get 6 ATP
(so, just from going from pyruvate to acetyl-Coa, gives 6 ATP); and then with TCA, get 24
ATP’s. 6 + 24 = 30 ATP; the total you can get from completely metabolizing glucose is 38 ATP; so, if you are thiamine def, you are out 30 ATP’s; so, the main prob of thiamine def is
c) In thiamine def you’ll see foot drop (dry beriberi), and pitting edema (wet beriberi). How
does this explain wet/dry beriberi?
1) Dry beriberi = peripheral neuropathy, and refers to Wernicke’s korsakoff psychosis
(can’t remember old and new things – like an exam – ie “used to know that, but can’t
remember now”; a memory problem). It takes a lot of ATP for synthesis of myelin;
without myelin, you will get peripheral neuropathy and foot drop (due to common
peroneal palsy), can get wrist drop (radial nerve palsy), and claw hand (ulnar nerve palsy).
Wernicke’s encephalopathy is confusion, ataxia, and nystagmus. All of these are due to
2) Wet beriberi = heart failure; MCC thiamine def = alcohol (not polished rice). Alcoholics
are the MC people with thiamine def. Wet beriberi is referring to cardiomyopathy –
cause: LHF went into RHF which lead to pitting edema. Heart needs ATP to function,
therefore, the pt with have congestive cardiomyopathy; their heart will have biventricular
enlargement (the whole chest will be heart), with left and right HF (pitting edema is a sign
of right HF due to increased hydrostatic pressure behind the failed heart). If you give IV
thiamine, can reverse; and in some cases it’s related to toxicity of alcohol, and cannot
d) Example: pt in ER given IV of 5% dextrose and normal saline; all of sudden, pt develops
confusion, nystagmus, and ataxia, and opthalmaplegia. Diagnosis: subclinical thiamine
deficiency. As soon as the glucose was hung up, the pyruvate went to acetyl CoA and used
the rest of thiamine...then went into acute Wernicke’s encephalopathy. Therefore, moral of
the story: give IV thiamine before hanging up IV glucose, especially in ER.
f) When people come in comatose or semicomatose, several things you always do: 1) 50%
glucose if a hypoglycemia problem 2) naloxone (OD) 3) IV thiamine
Vitamin B (3iacin):
Slide: Rash in sun exposed area = pellagra (aka dermatitis), due to niacin def (also diarrhea,
dermatitis, dementia); hyperpigmentation in sun-exposed areas = Cassel’s necklace
NAD/NADP rxns (N stands for nicotinamide, and the nicotinamide was derived from niacin).
Therefore, all the oxidation rxns rxn’s are niacin dependent. Example: pyruvate to acetyl
CoA = went from NAD to NADH and niacin is involved here.
Tryptophan can used in synthesizing niacin and serotonin (why it’s an essential aa); but it’s
not the main source of niacin, but a good source.
Nicotinic acid = least expensive lipid lowering drug; see the flushing assoc with it; supposed
to take aspirin with it to remove the flushing related to nicotinic acid (used in treating
familial hyperlipidemia), it is the DOC for elevated